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When changing)-23.2 ( )]TJ -0.018 Tc 0 Tw 0 -1.03 Td [(posit)0.5 (ions,)0.5 ( )0.5 (sit)0.5 ( )0.5 (upright)0.5 ( )0.5 (f)0.5 (or )0.6 (a )0.5 (f)0.5 (ew )0.5 (minut)0.5 (es )0.5 (bef)0.5 (ore )0.5 (st)0.5 (anding )0.5 (t)0.5 (o )0.5 (help )0.5 (prevent)0.5 ( )0.5 (t)0.5 (his.)]TJ 0 Tc /Span<>> BDC -1.214 -1.246 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.015 Tc 0.017 Tw 1.8 0 Td (Decreased white blood cell count.)Tj /C2_0 1 Tf 0.015 Tw [<0BD8>-0.6 <0003>0.9 <0037002B0024002F00320030002C00270003>-17.1 <0046004400510003>-17.1 <004600440058005600480003>-17.1 <0047004800460055004800440056004800470003>-17.1 <005A004B004C005700480003>-17.1 <0045004F0052005200470003>-17.1 <00460048004F004F0003>-17.1 <004600520058005100570056000F0003>-17 <004C00510046004F00580047004C0051004A0003>-17.1 <0051004800580057005500520053004B004C004F00560011>-14.8 <0003>]TJ -0.021 Tc 0.021 Tw 0 -1.03 Td [<0031004800580057005500520053004B004C004F00560003>13.9 <0044005500480003>13.9 <00440003>13.9 <0057005C005300480003>14 <005200490003>14 <005A004B004C005700480003>13.9 <0045004F0052005200470003>14 <00460048004F004F0003>14 <0057004B004400570003>14 <004C00560003>14 <004C005000530052005500570044005100570003>14 <004C00510003>14 <00BF004A004B0057004C0051004A0003>14 <004500440046005700480055004C0044004F0003>14 <004C00510049004800460057004C00520051005600110003>32.1 <003C>91.7 <0052005800550003>14 <004B00480044004F0057004B00460044005500480003>14 <0053005500520059004C0047004800550003>13.9 <0056004B00520058004F0047>-21.1 <0003>]TJ /TT1 1 Tf -0.02 Tc -0.014 Tw 0 -1.03 Td [(check your white blood count before and regularly while you take )18.3 (THALOMID. 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If your platelets are too low)54.9 (, your healthcare provider)-22 ( )]TJ -0.019 Tc 0 -1.03 Td [(may lower your dose, delay your dose, or completely stop treatment. )17.9 (T)110.9 (ell your healthcare provider if you have signs and)-19.1 ( )]TJ -0.018 Tc 0 Tw 0 -1.03 Td [(symptoms )0.5 (of )0.6 (bleeding )0.5 (such )0.5 (as:)]TJ ET 1 g /GS0 gs 45.5 500.141 261 -14.48 re 306.5 500.141 261 -14.48 re 45.5 485.661 261 -14.48 re 306.5 485.661 261 -14.48 re 45.5 471.181 261 -14.48 re 306.5 471.181 261 -14.48 re f BT 0 g /GS1 gs 0 Tc /Span<>> BDC 10 0 0 10 69.3567 489.2611 Tm ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(small )0.5 (red )0.5 (or )0.5 (purple )0.5 (spot)0.5 (s )0.5 (on )0.5 (your )0.5 (body)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(bright)0.5 ( )0.5 (red )0.5 (or )0.5 (t)0.5 (ar )0.5 (like )0.5 (st)0.5 (ools)]TJ 0 Tc /Span<>> BDC -27.314 -1.448 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(unusual )0.5 (bleeding )0.5 (or bruising)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(vomit)0.5 (ing )0.5 (or )0.5 (coughing )0.5 (up )0.5 (blood)]TJ 0 Tc /Span<>> BDC -27.314 -1.448 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 0.018 Tw 1.8 0 Td (nosebleeds)Tj 0 Tc 0 Tw /Span<>> BDC -3.014 -1.498 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.016 Tc 0.014 Tw 1.8 0 Td [(Increased HIV vir)-0.6 (us)-0.6 ( in the blood.)]TJ /C2_0 1 Tf 0.016 Tw [<0BD8>-0.8 <0003>-14.1 <002C00490003>-14.1 <005C00520058>-0.6 <0003>-14 <0044005500480003>-14.1 <002B002C00390003>-14 <005300520056004C0057004C00590048000F0003>-14.1 <005C0052005800550003>-14.1 <004B00480044004F0057004B00460044005500480003>-14 <0053>-0.6 <005500520059004C0047004800550003>-14.1 <0056004B00520058004F>-0.6 <00470003>-14.1 <0046004B00480046004E0003>-14.1 <005C0052005800550003>-14 <0059004C00550044004F0003>-14.1 <004F0052004400470003>-14.1 <00440049005700480055>-16 <0003>]TJ /TT1 1 Tf -0.018 Tc 0 Tw 0 -1.03 Td [(one )0.5 (mont)0.5 (h )0.5 (and )0.5 (t)0.5 (hree mont)0.5 (hs )0.5 (of)0.5 ( )0.5 (t)0.5 (reat)0.5 (ment,)0.6 ( )0.5 (then )0.5 (every )0.5 (3 )0.5 (mont)0.5 (hs )0.5 (af)0.5 (t)0.5 (er )0.5 (t)0.5 (hat)0.5 (.)]TJ 0 Tc /Span<>> BDC -1.214 -1.246 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.002 Tc 0.083 Tw 1.8 0 Td (Slow heartbeat \(bradycardia\).)Tj /C2_0 1 Tf 0.002 Tw [<0BD8>-0.7 <0003>-64.9 <0037>110.8 <0048004F004F0003>-82.9 <005C0052005800550003>-82.9 <004B00480044004F0057004B00460044005500480003>-82.9 <0053005500520059004C0047004800550003>-82.9 <004C00490003>-83 <005C005200580003>-82.9 <004B0044005900480003>-82.9 <00440003>-82.9 <0056004F0052005A0003>-82.9 <004B00480044005500570045004800440057000F0003>-82.9 <00490044004C00510057004C0051004A000F0003>-82.9 <0047004C005D005D004C00510048005600560003>-82.9 <00520055>-2 <0003>]TJ /TT1 1 Tf -0.018 Tc 0 Tw 0 -1.03 Td [(short)0.5 (ness )0.5 (of)0.5 ( )0.5 (breat)0.5 (h.)]TJ 0 Tc /Span<>> BDC -1.214 -1.246 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.022 Tc -0.014 Tw 1.8 0 Td (Severe skin reactions and severe allergic reactions.)Tj /C2_0 1 Tf 0.022 Tw [<0BD8>-0.8 <0003>13.7 <0036004800590048005500480003>13.7 <0056004E004C00510003>13.8 <00550048004400460057004C0052005100560003>13.7 <0044005100470003>13.7 <0056004800590048005500480003>13.8 <0044004F004F00480055004A004C00460003>13.8 <00550048004400460057004C0052005100560003>13.7 <0046004400510003>13.7 <004B00440053005300480051>-22.1 <0003>]TJ /TT1 1 Tf -0.018 Tc 0 Tw 0 -1.03 Td [(wit)0.5 (h )18.6 (THALO)0.5 (MI)0.5 (D )0.5 (and )0.5 (may )0.5 (cause )0.6 (deat)0.5 (h.)]TJ /TT0 1 Tf 0.002 Tc 0.099 Tw 0 -1.21 Td [(Cal)0.6 (l)0.7 ( )0.5 (yo)0.6 (u)0.7 (r )0.5 (h)0.7 (eal)0.7 (th)0.7 (care )0.5 (p)0.7 (ro)0.7 (vi)0.7 (d)0.6 (er )0.5 (ri)0.6 (g)0.7 (h)0.7 (t )0.5 (aw)0.7 (ay )0.5 (i)0.6 (f)0.5 ( )0.5 (yo)0.6 (u)0.7 ( )0.5 (d)0.7 (evel)0.7 (o)0.6 (p)0.7 ( )0.5 (an)0.7 (y )0.5 (o)0.7 (f)0.5 ( )0.5 (t)0.5 (h)0.6 (e )0.5 (f)0.5 (o)0.6 (l)0.7 (l)0.7 (o)0.6 (w)0.7 (i)0.7 (n)0.6 (g)0.7 ( )0.5 (si)0.7 (g)0.7 (n)0.6 (s )0.5 (o)0.6 (r )0.5 (symp)0.7 (t)0.5 (o)0.6 (ms )0.5 (d)0.7 (u)0.7 (ri)0.7 (n)0.6 (g)2.2 ( )]TJ -0.018 Tc 0 Tw 0 -1.03 Td [(treatmen)0.5 (t )0.5 (w)0.5 (i)0.5 (th)0.5 ( )0.5 (T)0.5 (HAL)0.5 (O)0.5 (MI)0.6 (D:)]TJ /C2_0 1 Tf 0 Tc 12.3 0 Td <0BD8>Tj ET 1 g /GS0 gs 45.5 363.448 261 -14.48 re 306.5 363.448 261 -14.48 re 45.5 348.967 261 -14.48 re 306.5 348.967 261 -14.48 re f BT 0 g /GS1 gs /TT1 1 Tf /Span<>> BDC 10 0 0 10 69.3567 352.5675 Tm ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(a )0.5 (red, )0.5 (it)0.5 (chy)74.6 (,)0.5 ( skin )0.5 (rash)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(severe )0.5 (it)0.5 (ching)]TJ 0 Tc /Span<>> BDC -27.314 -1.448 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(peeling )0.5 (of)0.5 ( )0.5 (your )0.5 (skin )0.5 (or )0.5 (blist)0.5 (ers)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 0.018 Tw 1.8 0 Td [(f)0.5 (ever)]TJ /TT0 1 Tf -0.024 Tc -0.014 Tw -27.9 -1.462 Td [(Get )0.7 (emergency )0.6 (medical )0.6 (help )0.6 (right )0.6 (away )0.6 (if )0.7 (you )0.6 (develop )0.6 (any )0.7 (of )0.7 (the )0.6 (following )0.7 (signs )0.7 (or )0.6 (symptoms )0.6 (during )0.7 (treatment)-24 ( )]TJ -0.018 Tc 0 Tw 0 -1.03 Td [(w)0.5 (i)0.5 (th)0.5 ( )0.5 (T)0.5 (HAL)0.5 (O)0.5 (MI)0.5 (D:)]TJ /C2_0 1 Tf 0 Tc 7.649 0 Td <0BD8>Tj ET 1 g /GS0 gs 45.5 309.516 261 -14.48 re 306.5 309.516 261 -14.48 re 45.5 295.036 261 -14.48 re 306.5 295.036 261 -14.48 re 45.5 280.556 261 -14.48 re 306.5 280.556 261 -14.48 re f BT 0 g /GS1 gs /TT1 1 Tf /Span<>> BDC 10 0 0 10 69.3567 298.636 Tm ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(swelling )0.5 (of)0.5 ( )0.5 (your )0.5 (lips,)0.5 ( )0.5 (mout)0.5 (h, )0.6 (t)0.5 (ongue,)0.5 ( )0.5 (or )0.5 (t)0.5 (hroat)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(raised red )0.5 (areas )0.5 (on your )0.5 (skin )0.5 (\(hives\))]TJ 0 Tc /Span<>> BDC -27.314 -1.448 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(t)0.5 (rouble )0.5 (breat)0.5 (hing )0.5 (or )0.5 (swallowing)]TJ 0 Tc /Span<>> BDC 24.886 0 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(a )0.5 (very )0.5 (f)0.5 (ast)0.5 ( )0.5 (heart)0.5 (beat)]TJ 0 Tc /Span<>> BDC -1.214 -1.448 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(you )0.5 (f)0.5 (eel )0.5 (dizzy )0.5 (or )0.5 (f)0.5 (aint)]TJ 0 Tc /Span<>> BDC -29.114 -1.498 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.018 Tc 1.8 0 Td [(Sei)0.5 (zu)0.5 (res. )0.6 (T)74.7 (el)0.5 (l)0.5 ( )0.5 (yo)0.5 (u)0.5 (r )0.5 (heal)0.5 (th)0.5 (care )0.5 (p)0.5 (ro)0.5 (vi)0.5 (d)0.5 (er )0.5 (ri)0.5 (g)0.5 (h)0.5 (t )0.5 (aw)0.5 (ay )0.5 (i)0.5 (f )0.5 (yo)0.5 (u)0.5 ( )0.5 (h)0.5 (ave a )0.5 (sei)0.5 (zu)0.5 (re )0.5 (w)0.5 (h)0.5 (i)0.5 (l)0.5 (e )0.5 (taki)0.5 (n)0.5 (g )0.5 (T)0.5 (HAL)0.5 (OMI)0.5 (D.)]TJ /C2_0 1 Tf 0 Tc 43.715 0 Td <0BD8>Tj /TT1 1 Tf /Span<>> BDC -44.929 -1.246 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.02 Tc -0.014 Tw 1.8 0 Td [(T)74.6 (umor L)37.4 (ysis Syndrome \(TLS\).)]TJ /C2_0 1 Tf 0.02 Tw [<0BD80003>32.4 <0037002F00360003>14.2 <004C00560003>14.3 <0046004400580056004800470003>14.2 <0045005C0003>14.3 <0057004B00480003>14.3 <00490044005600570003>14.3 <0045005500480044004E00470052005A00510003>14.3 <005200490003>14.3 <0046004400510046004800550003>14.2 <00460048004F004F005600110003>32.4 <0037002F00360003>14.3 <0046004400510003>14.3 <004600440058005600480003>14.3 <004E004C004700510048005C0003>14.3 <00490044004C004F0058005500480003>14.2 <004400510047>-20.1 <0003>]TJ /TT1 1 Tf -0.018 Tc -0.011 Tw 0 -1.03 Td [(t)0.5 (he need f)0.5 (or )0.5 (dialysis t)0.5 (reat)0.5 (ment)0.5 (,)0.5 ( abnormal heart)0.5 ( rhyt)0.5 (hm,)0.5 ( seizure )0.5 (and somet)0.5 (imes deat)0.5 (h. )18.5 (Y)92.2 (our )0.5 (healt)0.5 (hcare provider )0.5 (may do)-18.1 ( )]TJ 0 Tw 0 -1.03 Td [(blood )0.5 (t)0.5 (est)0.5 (s )0.5 (t)0.5 (o )0.5 (check )0.5 (you )0.5 (f)0.5 (or )18.6 (TLS.)]TJ 0 Tc /Span<>> BDC -1.214 -1.246 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.02 Tc -0.014 Tw 1.8 0 Td [(Bi)0.7 (rth)0.7 ( )0.5 (co)0.7 (n)0.6 (t)0.5 (ro)0.6 (l)0.7 ( )0.5 (ri)0.7 (sks.)]TJ /C2_0 1 Tf 0.02 Tw 8.453 0 Td [<0BD80003>14.5 <0026004800550057>0.7 <0044004C00510003>14.6 <0045004C0055>0.5 <0057>0.6 <004B0003>14.5 <0046>0.5 <005200510057>0.7 <00550052004F0003>14.5 <0050>0.5 <00480057>0.6 <004B005200470056>0.5 <0003>14.5 <0050>0.5 <0044005C>0.5 <0003>14.5 <005300520056>0.5 <00480003>14.5 <00440003>14.6 <004B004C004A004B00480055>0.5 <0003>14.5 <0055>0.5 <004C0056>0.5 <004E0003>14.6 <00520049>0.7 <0003>14.5 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(T)0.5 (HALO)0.5 (MI)0.5 (D.)]TJ /TT0 1 Tf 0 -1.386 Td [(F)0.5 (emal)0.5 (es )0.5 (mu)0.5 (st )0.5 (n)0.5 (o)0.5 (t )0.5 (g)0.5 (et )0.5 (p)0.5 (reg)0.5 (n)0.5 (an)0.5 (t:)]TJ /C2_0 1 Tf 0 Tc 14.637 0 Td <0BD8>Tj /TT1 1 Tf /Span<>> BDC -14.051 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(F)0.5 (or )0.5 (at)0.5 ( )0.5 (least)0.5 ( )0.5 (4 )0.5 (weeks )0.6 (bef)0.5 (ore )0.5 (st)0.5 (art)0.5 (ing )18.6 (T)0.5 (HALO)0.5 (MI)0.5 (D)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc -0.018 Tw 1.8 0 Td [(W)0.5 (hile )-17.5 (taking )0.5 (T)0.5 (HALO)0.5 (MI)0.5 (D)]TJ 0 Tc 0 Tw /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(During )0.5 (any breaks )0.5 (\(int)0.5 (errupt)0.5 (ions\) )0.5 (in )0.5 (your )0.5 (t)0.5 (reat)0.5 (ment)0.5 ( )0.5 (wit)0.5 (h )18.6 (T)0.5 (HALO)0.5 (MI)0.5 (D)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(F)0.5 (or )0.5 (at)0.5 ( )0.5 (least)0.5 ( )0.5 (4 )0.5 (weeks )0.6 (af)0.5 (t)0.5 (er )0.5 (st)0.5 (opping )18.5 (T)0.5 (HALO)0.5 (MI)0.5 (D)]TJ /TT0 1 Tf -1.8 -1.386 Td [(F)0.5 (emal)0.5 (es )0.5 (w)0.5 (ho)0.5 ( )0.5 (can)0.5 ( )0.5 (b)0.5 (eco)0.5 (me )0.6 (preg)0.5 (n)0.5 (an)0.5 (t:)]TJ /C2_0 1 Tf 0 Tc 16.658 0 Td <0BD8>Tj /TT1 1 Tf /Span<>> BDC -16.073 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.006 Tc 0.06 Tw 1.8 0 Td [(Will have pregnancy tests weekly for 4 weeks, then every 4 weeks if your\ menstrual cycle is regular)55.4 (, or every)-6 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(2 )0.5 (weeks )0.6 (if)0.5 ( )0.5 (your )0.5 (menst)0.5 (rual cycle )0.5 (is irregular)55.5 (.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(I)0.5 (f)0.5 ( )0.5 (you )0.5 (miss )0.5 (your )0.5 (period )0.5 (or )0.5 (have )0.5 (unusual )0.5 (bleeding,)0.5 ( )0.5 (you )0.5 (will )0.5 (need )0.6 (t)0.5 (o )0.5 (have )0.5 (a )0.5 (pregnancy )0.5 (t)0.5 (est)0.5 ( )0.5 (and )0.5 (receive )0.5 (counseling.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 0.012 Tw 1.8 0 Td [(Must)0.5 ( )0.6 (agree )0.6 (t)0.5 (o )0.6 (use )0.5 (t)0.5 (wo )0.5 (accept)0.5 (able )0.6 (f)0.5 (orms )0.6 (of)0.5 ( )0.5 (birt)0.5 (h )0.6 (cont)0.5 (rol )0.5 (at)0.5 ( )0.5 (t)0.5 (he )0.5 (same )0.6 (t)0.5 (ime,)0.5 ( )0.5 (f)0.5 (or )0.6 (at)0.5 ( )0.5 (least )0.6 (4 )0.5 (weeks )0.6 (bef)0.5 (ore,)0.5 ( )0.6 (while )0.6 (t)0.5 (aking,)-17.9 ( )]TJ 0 Tw 0 -1.044 Td [(during )0.5 (any )0.5 (breaks )0.5 (\(int)0.5 (errupt)0.5 (ions\) )0.5 (in )0.5 (your )0.5 (t)0.5 (reat)0.5 (ment)0.5 (,)0.5 ( )0.5 (and )0.5 (f)0.5 (or )0.5 (at)0.5 ( )0.5 (least)0.5 ( )0.5 (4 )0.5 (weeks )0.5 (af)0.5 (t)0.5 (er )0.5 (st)0.5 (opping )18.5 (T)0.5 (HALO)0.5 (MI)0.5 (D.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj -0.018 Tc 0.018 Tw 1.8 0 Td [<0037>111.3 <0044004F004E0003>9.4 <005A004C0057>0.5 <004B0003>9.4 <005C0052005800550003>9.4 <004B00480044004F0057>0.5 <004B00460044005500480003>9.4 <0053005500520059004C0047004800550003>9.4 <0057>0.5 <00520003>9.4 <00BF005100470003>9.4 <005200580057>0.5 <0003>9.4 <00440045005200580057>0.6 <0003>9.4 <005200530057>0.5 <004C0052005100560003>9.5 <0049>0.5 <005200550003>9.4 <004400460046004800530057>0.5 <00440045004F00480003>9.4 <0049>0.5 <00520055005000560003>9.4 <00520049>0.5 <0003>9.4 <0045004C00550057>0.5 <004B0003>9.5 <0046005200510057>0.5 <00550052004F0003>9.4 <0057>0.5 <004B00440057>0.5 <0003>9.4 <005C005200580003>9.4 <00500044005C0003>9.4 <0058005600480003>9.4 <0057>0.5 <0052>-18.1 <0003>]TJ /TT1 1 Tf 0 Tw 0 -1.044 Td [(prevent )0.5 (pregnancy )0.5 (bef)0.5 (ore,)0.5 ( )0.5 (during,)0.5 ( )0.5 (and )0.5 (af)0.5 (t)0.5 (er )0.5 (t)0.5 (reat)0.5 (ment )0.6 (wit)0.5 (h )18.5 (T)0.5 (HALO)0.5 (MI)0.5 (D.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.02 Tc -0.014 Tw 1.8 0 Td [(Stop taking )17.9 (THALOMID and call your healthcare provider right away if you have unprot\ ected sex or if you think your)-20 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(birt)0.5 (h )0.5 (cont)0.5 (rol )0.5 (has f)0.6 (ailed.)]TJ /TT0 1 Tf -0.012 Tc 0.031 Tw -1.8 -1.224 Td [(If you become pregnant while taking THALOMID, stop taking it right away \ and call your healthcare provider)55.2 (.)]TJ /C2_0 1 Tf -0.037 Tc 0.037 Tw 50.294 0 Td [<0BD8>-0.8 <0003>]TJ /TT1 1 Tf 0 Tc 0 Tw 0.047 0 Td ( )Tj 0.001 Tc 0.095 Tw -50.341 -1.044 Td [(I)0.5 (f)0.5 ( )0.6 (your )0.6 (healt)0.5 (hcare )0.6 (provider )0.6 (is )0.6 (not)0.5 ( )0.6 (available,)0.5 ( )0.6 (you )0.5 (should )0.6 (call )0.5 (Celgene )0.6 (Cust)0.6 (omer )0.5 (Care )0.5 (Cent)0.5 (er )0.6 (at)0.5 ( )0.6 (1-888-423-5436.)1.2 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(Healt)0.5 (hcare providers )0.5 (and )0.6 (pat)0.5 (ient)0.5 (s )0.5 (should )0.5 (report)0.5 ( )0.5 (all )0.5 (cases )0.5 (of)0.5 ( )0.5 (pregnancy )0.5 (t)0.5 (o:)]TJ 0 Tc /Span<>> BDC 0.586 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(F)0.5 (DA)55.6 ( )0.5 (MedW)37.6 (at)0.5 (ch )0.5 (at)0.5 ( )0.5 (1-800-F)0.5 (DA-1088, )0.6 (and)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc 1.8 0 Td [(Celgene )0.5 (Corporat)0.5 (ion )0.5 (at)0.5 ( )0.5 (1-888-423-5436)]TJ -0.01 Tc 0.043 Tw -3.6 -1.44 Td [(There is a pregnancy exposure registry that monitors the outcomes of fem\ ales who take )17.9 (THALOMID during pregnancy)73.9 (,)-9.8 ( )]TJ -0.014 Tc 0.019 Tw 0 -1.044 Td [(or if)0.5 ( t)0.5 (heir male part)0.6 (ner t)0.6 (akes )18 (T)0.6 (HALO)0.6 (MI)0.6 (D and t)0.5 (hey are exposed during pregnancy)74.6 (.)0.6 ( )18 (Y)92.2 (ou can enroll in t)0.6 (his regist)0.5 (ry by calling)-14.2 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(Celgene )0.5 (Corporat)0.5 (ion )0.5 (at)0.5 ( )0.5 (t)0.5 (he )0.6 (phone )0.5 (number )0.5 (list)0.5 (ed )0.5 (above.)]TJ /TT0 1 Tf 1.8 -1.296 Td [(T)0.5 (HAL)0.5 (O)0.5 (MI)0.5 (D )0.5 (can)0.5 ( )0.5 (p)0.5 (ass )0.5 (i)0.5 (n)0.5 (to )0.5 (h)0.5 (u)0.5 (man )0.5 (semen)0.5 (:)]TJ /C2_0 1 Tf 0 Tc 18.657 0 Td <0BD8>Tj /TT1 1 Tf /Span<>> BDC -18.071 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc -0.013 Tw 1.8 0 Td [(Males,)0.5 ( including t)0.5 (hose who have had a vasect)0.5 (omy)74.6 (,)0.5 ( must)0.5 ( always use a lat)0.5 (ex or synt)0.5 (het)0.5 (ic condom during any sexual)-18.2 ( )]TJ 0.013 Tw 0 -1.044 Td [(cont)0.5 (act)0.5 ( wit)0.5 (h a pregnant)0.5 ( f)0.5 (emale or a female t)0.5 (hat)0.5 ( can become pregnant)0.5 ( while t)0.5 (aking )18 (T)0.5 (HALO)0.5 (MI)0.5 (D,)0.5 ( during any breaks)-18 ( )]TJ 0 Tw 0 -1.044 Td [(\(int)0.5 (errupt)0.5 (ions\) )0.5 (in )0.5 (your )0.5 (t)0.5 (reat)0.5 (ment)0.5 ( )0.5 (wit)0.5 (h )18.5 (T)0.5 (HALO)0.5 (MI)0.5 (D,)0.5 ( )0.5 (and )0.5 (f)0.5 (or )0.5 (up )0.6 (t)0.5 (o )0.5 (4 )0.5 (weeks )0.5 (af)0.6 (ter )0.5 (st)0.5 (opping )18.6 (T)0.5 (HALOMI)0.5 (D.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.006 Tc 0.064 Tw 1.8 0 Td [(D)-0.6 (o n)-0.6 (ot have un)-0.6 (protected)-0.6 ( sexu)-0.6 (al contact w)-0.6 (ith a femal)-0.6 (e wh)-0.6 (o i)-0.6 (s o)-0.6 (r cou)-0.6 (ld be)-0.6 (co)-0.6 (me)-0.6 ( p)-0.6 (re)-0.6 (gnan)-0.6 (t. )18.3 (T)110.6 (ell)-0.6 ( yo)-0.6 (ur h)-0.6 (eal)-0.6 (thcare)-6.1 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(provider )0.5 (if)0.5 ( )0.5 (you )0.5 (do )0.5 (have )0.5 (unprot)0.5 (ect)0.5 (ed )0.5 (sexual )0.5 (cont)0.5 (act)0.5 ( )0.5 (wit)0.5 (h )0.5 (a )0.5 (f)0.5 (emale )0.5 (who )0.5 (is )0.5 (or )0.5 (could )0.5 (become )0.5 (pregnant)0.5 (.)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT1 1 Tf -0.018 Tc -0.006 Tw 1.8 0 Td [(Do not)0.5 ( donate sperm while t)0.5 (aking )18.5 (T)0.5 (HALO)0.5 (MID,)0.5 ( during any breaks \(int)0.5 (errupt)0.5 (ions\) in your t)0.5 (reat)0.5 (ment)0.5 (,)0.5 ( and f)0.5 (or 4 weeks)-18 ( )]TJ -0.023 Tc -0.014 Tw 0 -1.044 Td [(after stopping )18.2 (THALOMID. If a female becomes pregnant with your sperm, the baby may be \ exposed to )18.2 (THALOMID)-23.2 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(and )0.5 (may be )0.5 (born )0.5 (wit)0.5 (h )0.6 (birt)0.5 (h )0.5 (def)0.5 (ect)0.5 (s.)]TJ /TT0 1 Tf -1.8 -1.224 Td [(Men)0.5 (,)0.5 ( )0.5 (i)0.5 (f )0.5 (yo)0.5 (u)0.5 (r )0.5 (femal)0.5 (e )0.5 (p)0.5 (artn)0.5 (er )0.5 (b)0.5 (eco)0.5 (mes )0.5 (p)0.5 (reg)0.5 (n)0.5 (an)0.5 (t,)0.5 ( )0.5 (you)0.6 ( sh)0.5 (o)0.5 (u)0.5 (l)0.5 (d)0.5 ( )0.5 (cal)0.5 (l)0.5 ( )0.5 (yo)0.5 (u)0.5 (r h)0.5 (eal)0.5 (th)0.5 (care )0.5 (p)0.5 (ro)0.5 (vi)0.5 (d)0.5 (er )0.5 (ri)0.5 (g)0.5 (h)0.5 (t )0.5 (aw)0.5 (ay)74.4 (.)]TJ /C2_0 1 Tf 0 Tc 45.437 0 Td <0BD8>Tj /TT1 1 Tf /Span<>> BDC -46.651 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <0194>Tj /TT0 1 Tf -0.015 Tc 0.017 Tw 1.8 0 Td (Blood clots.)Tj /C2_0 1 Tf 0.015 Tw [<0BD8>-0.6 <0003>-16.8 <0033004800520053004F00480003>-16.8 <005A004C0057004B0003>-16.8 <00500058004F0057004C0053004F00480003>-16.8 <0050005C0048004F0052005000440003>-16.9 <000B00300030000C0003>-16.9 <005A004B00520003>-16.9 <00570044004E00480003>1.2 <0037002B0024002F00320030002C00270003>-16.8 <00500044005C0003>-16.8 <004B0044005900480003>-16.9 <004400510003>-16.8 <004C005100460055004800440056004800470003>-16.8 <0055004C0056004E0003>-16.8 <0049005200550003>-16.8 <0045004F0052005200470003>-16.9 <0046004F0052005700560003>-16.9 <004C0051>-15.1 <0003>]TJ /TT1 1 Tf -0.022 Tc -0.014 Tw 0 -1.044 Td [(their arteries, veins, and lungs. )17.9 (This risk is even higher if you take the medicine dexamethasone with )17.9 (THALOMID to treat)-21.8 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(your )0.5 (MM.)0.5 ( )0.5 (Heart)0.5 ( )0.5 (at)0.5 (t)0.5 (acks )0.5 (and )0.5 (st)0.5 (rokes )0.5 (may )0.5 (also )0.5 (happen )0.5 (if)0.5 ( )0.5 (you )0.5 (t)0.5 (ake )18.5 (T)0.5 (HALO)0.5 (MI)0.5 (D )0.5 (wit)0.5 (h )0.6 (dexamet)0.5 (hasone.)]TJ -0.015 Tc 0.015 Tw 0 -1.224 Td [(Before taking )17.9 (THALOMID, tell your healthcare provider about all the medicines you take\ . Certain other medicines can)-15.1 ( )]TJ -0.018 Tc 0 Tw 0 -1.044 Td [(also )0.5 (increase )0.5 (your )0.5 (risk )0.5 (f)0.5 (or )0.5 (blood )0.5 (clot)0.5 (s.)]TJ -0.003 Tc 0.078 Tw 0 -1.188 Td [(Call your healthcare provider or get medical help right away if you get \ any of the following during treatment with)-3.1 ( )]TJ -0.018 Tc 0.018 Tw 0 -1.044 Td [(T)0.5 (HALO)0.5 (MI)0.5 (D:)]TJ 0 Tc 0 Tw /Span<>> BDC 0.586 -1.224 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT0 1 Tf -0.012 Tc 0.028 Tw 1.8 0 Td [(S)0.6 (i)0.7 (g)0.7 (n)0.7 (s o)0.7 (r symp)0.7 (t)0.5 (o)0.7 (ms o)0.7 (f)0.5 ( a b)0.7 (l)0.7 (o)0.7 (o)0.8 (d)0.7 ( cl)0.7 (o)0.7 (t)0.6 ( i)0.7 (n)0.8 ( t)0.5 (h)0.8 (e l)0.7 (u)0.7 (n)0.7 (g)0.7 (,)0.8 ( arm,)0.7 ( o)0.8 (r l)0.7 (eg)0.7 ( may)0.5 ( i)0.7 (n)0.7 (cl)0.7 (u)0.8 (d)0.7 (e:)]TJ /C2_0 1 Tf 0.012 Tw 33.297 0 Td [<0BD80003>-28.3 <0056>0.5 <004B>0.5 <00520055>0.6 <0057>0.7 <005100480056>0.5 <0056>0.6 <0003>-28.2 <00520049>0.6 <0003>-28.2 <00450055>0.5 <004800440057>0.8 <004B000F>0.8 <0003>-28.3 <0046>0.6 <004B00480056>0.5 <0057>0.7 <0003>-28.2 <00530044004C0051000F>0.8 <0003>-28.3 <00520055>-12 <0003>]TJ /TT1 1 Tf -0.018 Tc 0 Tw -33.297 -1.044 Td [(arm )0.5 (or )0.5 (leg )0.5 (swelling)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT0 1 Tf -0.017 Tc 0.014 Tw 1.8 0 Td (Signs or symptoms of a heart attack may include:)Tj /C2_0 1 Tf 0.017 Tw [<0BD8>-0.6 <0003>-13.8 <0046004B0048005600570003>-13.8 <00530044004C00510003>-13.8 <0057004B004400570003>-13.9 <00500044005C0003>-13.8 <0056005300550048004400470003>-13.8 <005700520003>-13.8 <0057004B00480003>-13.8 <0044005500500056000F0003>-13.8 <005100480046004E000F0003>-13.8 <004D0044005A>54.9 <000F0003>-13.8 <004500440046004E000F0003>-13.8 <00520055>-17 <0003>]TJ /TT1 1 Tf -0.018 Tc 0 Tw 0 -1.044 Td [(st)0.5 (omach )0.5 (area \(abdomen\),)0.5 ( )0.5 (f)0.5 (eeling )0.5 (sweat)0.5 (y)74.5 (,)0.5 ( )0.5 (short)0.5 (ness )0.5 (of)0.5 ( )0.5 (breat)0.5 (h,)0.5 ( )0.5 (f)0.5 (eeling )0.5 (sick )0.5 (or )0.5 (vomit)0.5 (ing)]TJ 0 Tc /Span<>> BDC -1.214 -1.26 Td ( )Tj EMC /C2_0 1 Tf -0.586 0 Td <017C>Tj /TT0 1 Tf -0.018 Tc 1.8 0 Td [(Si)0.5 (g)0.5 (n)0.5 (s o)0.5 (r symp)0.5 (to)0.5 (ms o)0.5 (f stro)0.5 (ke may i)0.5 (n)0.5 (cl)0.6 (ud)0.5 (e:)]TJ /C2_0 1 Tf 0.018 Tw [<0BD800030056005800470047004800510003005100580050004500510048005600560003005200550003005A00480044004E0051004800560056000F>0.5 <000300480056005300480046004C0044004F004F005C000300520051000300520051004800030056004C00470048000300520049>0.5 <00030057>0.5 <004B00480003004500520047005C>74.6 <000F>-17.9 <0003>]TJ /TT1 1 Tf 0 Tw 0 -1.044 Td [(severe )0.5 (headache )0.5 (or )0.5 (conf)0.5 (usion,)0.5 ( )0.5 (or )0.5 (problems )0.5 (wit)0.5 (h )0.5 (vision,)0.5 ( )0.5 (speech,)0.5 ( )0.5 (or )0.5 (balance)]TJ ET 4 M 36 36 540 695.808 re S endstream endobj 35 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q 0.5 w /GS1 gs q 1 0 0 1 324 726.2481 cm 0 0 m 69.042 0 l S Q q 1 0 0 1 324 691.8681 cm 0 0 m 33.943 0 l S Q q 1 0 0 1 324 649.1381 cm 0 0 m 81.566 0 l S Q q 1 0 0 1 324 606.4081 cm 0 0 m 24.212 0 l S Q q 1 0 0 1 324 572.0281 cm 0 0 m 65.056 0 l S Q q 1 0 0 1 324 529.298 cm 0 0 m 56.242 0 l S Q q 1 0 0 1 324 486.5681 cm 0 0 m 44.407 0 l S Q BT /T1_0 1 Tf -0.017 Tc 0.048 Tw 8 0 0 8 324 727.2481 Tm [(Increased HIV )37.2 (Viral Load)]TJ -0.002 Tc 0.121 Tw 0 -1.539 Td [(I)0.5 (nf)0.5 (o)0.5 (r)0.5 (m)0.5 ( HI)0.5 (V)0.5 ( s)0.5 (er)0.5 (o)0.5 (p)0.5 (os)0.5 (i)0.5 (t)0.5 (iv)0.5 (e)0.5 ( p)0.5 (a)-9.5 (ti)0.5 (e)0.5 (n)0.5 (ts)0.5 ( o)0.5 (f)0.5 ( t)0.5 (he)0.5 ( r)0.5 (i)0.5 (sk)0.5 ( o)0.5 (f)0.5 ( i)0.5 (nc)0.5 (r)0.5 (e)0.5 (as)0.5 (e)0.5 (d)0.5 ( vi)0.5 (r)0.5 (a)0.5 (l)0.5 ( lo)0.5 (a)0.5 (d)0.5 ( an)0.5 (d)0.5 ( t)0.5 (he)0.5 ( n)0.5 (e)0.5 (e)0.5 (d t)0.5 (o)-2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td (monitor viral load )Tj /T1_1 1 Tf [([see )37.2 (W)18.2 (arnings and Precaution)]TJ (s \(5.10\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw 0 -1.715 Td [(Brad)-9.8 (ycardia)]TJ -0.009 Tc 0.089 Tw 0 -1.539 Td [(Inform pa)-10 (tients of the risk of brad)-10 (ycardia and report signs and symptoms associa)-10 (ted)-9 ( )]TJ 0.016 Tc 0.213 Tw 0 -1.044 Td [(with this event to their healthcare provider for evalua)-9.8 (tion )]TJ /T1_1 1 Tf 0.176 Tw [([see W)18.1 (arnings )-37.1 (and)16 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (Precaution)Tj 0.048 Tw (s \(5.11\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw 0 -1.715 Td (Severe Cutaneous Reactions)Tj -0.006 Tc 0.106 Tw 0 -1.539 Td [(Inform )0.5 (pa)-10.2 (tients )0.5 (of )0.6 (the )0.5 (potential )0.5 (risk )0.5 (for )0.5 (severe )0.5 (skin )0.5 (reactions )0.5 (such )0.5 (as )0.5 (SJS,)36.8 ( )37.4 (TEN )0.5 (and)-6 ( )]TJ 0.001 Tc 0.137 Tw 0 -1.044 Td [(DRESS and report an)-9.7 (y signs and symptoms associa)-9.7 (ted with these events to their)1 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(healthcare provider for evalua)-9.7 (tion )]TJ /T1_1 1 Tf [([see )37.2 (W)18.2 (arnings and Precaution)]TJ (s \(5.12\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw 0 -1.715 Td (Seizures)Tj -0.009 Tc 0.087 Tw 0 -1.539 Td [(Inform pa)-9.6 (tients of the risk of seizures and report an)-9.6 (y seizure while taking )37.3 (THALOMID)-9 ( )]TJ /T1_1 1 Tf -0.017 Tc 0.048 Tw 0 -1.044 Td [([see )37.3 (W)18.2 (arnings and Precaution)]TJ (s \(5.13\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw 0 -1.715 Td [(T)74.2 (umor L)37.2 (ysis Syndrome)]TJ -0.012 Tc 0.074 Tw 0 -1.539 Td [(Inform pa)-10 (tients of the potential risk of tumor lysis syndrome and report an)-10 (y signs and)-12 ( )]TJ -0.007 Tc 0.101 Tw 0 -1.044 Td [(symptoms associa)-10.3 (ted with this event to their healthcare provider for evalua)-10.2 (tion )]TJ /T1_1 1 Tf 0.007 Tw [([see)-6.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(W)18.2 (arnings and Precaution)]TJ (s \(5.14\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw 0 -1.715 Td (Contraceptive Risks)Tj -0.007 Tc 0.097 Tw 0 -1.539 Td [(Inform pa)-9.6 (tients tha)-9.6 (t some contraceptive methods may pose a higher risk of adverse)-7 ( )]TJ -0.01 Tc 0.086 Tw 0 -1.044 Td [(effects or may be medically contraindica)-10.3 (ted in some pa)-10.3 (tients trea)-10.3 (ted with )37.1 (THALOMID)-10 ( )]TJ /T1_1 1 Tf -0.017 Tc 0.048 Tw 0 -1.044 Td [([see )37.3 (W)18.2 (arnings and Precautions \(5.15\),)37.2 ( Drug Interactions \(7)]TJ [(.4,)37.1 ( 7.7\)])]TJ /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw 0 -1.715 Td (Hypersensitivity)Tj -0.019 Tc 0.036 Tw 0 -1.539 Td [(Inform pa)-10.3 (tients of the potential for severe hypersensitivity reactions such as an\ gioedema)-19 ( )]TJ -0.004 Tc 0.114 Tw 0 -1.044 Td [(and ana)-10.1 (phylaxis to )36.8 (THALOMID.)36.9 ( Instruct pa)-10 (tients to contact their healthcare provider)-3.9 ( )]TJ 0.115 Tw 0 -1.044 Td [(right a)-10.1 (way for signs of a skin reaction.)36.9 ( )37.3 (Advise pa)-10.1 (tients to seek emergenc)19.9 (y medical)-3.9 ( )]TJ -0.014 Tc 0.064 Tw 0 -1.044 Td [(a)-9.9 (ttention )0.5 (for )0.5 (signs )0.5 (or )0.5 (symptoms )0.5 (of )0.5 (severe )0.5 (hypersensitivity )0.5 (reactions )]TJ /T1_1 1 Tf 0.027 Tw 24.787 0 Td [([see )0.5 (W)18.1 (arnings )-36.4 (and)-14.1 ( )]TJ -0.017 Tc 0.017 Tw -24.787 -1.044 Td (Precaution)Tj 0.048 Tw (s \(5.16\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.012 Tc 0.048 Tw 0 -3.811 Td [(Manufactured for Celgene Corpora)-9.8 (tion)]TJ 0 Tc 0 Tw 13.831 0 Td ( )Tj -0.012 Tc 0.011 Tw -13.831 -1.125 Td [(86 )-36.8 (Morris Avenue)]TJ 0 Tc 0 Tw 6.387 0 Td ( )Tj -0.012 Tc 0.048 Tw -6.387 -1.125 Td [(Summit,)37.2 ( NJ 07901)]TJ 0 Tc 0 Tw 6.848 0 Td ( )Tj -0.012 Tc 0.012 Tw -6.848 -1.125 Td (1-\(888\)-423-5436)Tj -0.017 Tc 0.017 Tw 0 -1.966 Td (THALOMID)Tj 0 Tc 0 Tw 5.6 0 0 5.6 354.6109 371.3021 Tm (\256)Tj -0.017 Tc 0.048 Tw 8 0 0 8 358.9945 368.6381 Tm [( and )37.3 (THALOMID REMS)]TJ 0 Tc 0 Tw 5.6 0 0 5.6 423.293 371.3021 Tm (\256)Tj -0.017 Tc 0.048 Tw 8 0 0 8 427.6766 368.6381 Tm [( are registered trademarks of Celgene Corpora)-9.7 (tion.)]TJ -12.96 -1.404 Td [(P)18.2 (a)-9.8 (t.)37.2 ( http://www)37.2 (.celgene.com/thera)-9.8 (pies)]TJ 0 -1.404 Td [(\251 1998-2021 Celgene Corpora)-9.8 (tion.)37.2 ( )37.2 (All Rights Reser)-17.8 (ved.)]TJ 0.017 Tw 0 -1.404 Td [(THALPL)92.3 (YPI.026/MG.025)]TJ ET q 1 0 0 1 36 705.1081 cm 0 0 m 76.223 0 l S Q q 1 0 0 1 36 587.1781 cm 0 0 m 83.173 0 l S Q q 1 0 0 1 36 536.0981 cm 0 0 m 110.335 0 l S Q q 1 0 0 1 36 485.0182 cm 0 0 m 82.984 0 l S Q q 1 0 0 1 36 433.9382 cm 0 0 m 63.303 0 l S Q q 1 0 0 1 36 391.2082 cm 0 0 m 109.108 0 l S Q q 1 0 0 1 36 348.4782 cm 0 0 m 34.463 0 l S Q q 1 0 0 1 36 314.0982 cm 0 0 m 52.559 0 l S Q BT 8 0 0 8 36 727.2481 Tm (\225)Tj /Span<>> BDC ( )Tj EMC -0.012 Tc 0.074 Tw 1.125 0 Td [(All pa)-10 (tients must be instructed to not dona)-10 (te blood while taking )37 (THALOMID and for)-12 ( )]TJ -0.02 Tc 0.036 Tw 0 -1.062 Td [(4 weeks follo)-9.9 (wing discontinua)-9.8 (tion of )37.1 (THALOMID )]TJ /T1_1 1 Tf [([see )37.1 (W)18.1 (arnings and Precautions \(5.1\)])]TJ /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw -1.125 -1.58 Td (THALOMID REMS Program)Tj 0.005 Tc 0.157 Tw 0 -1.539 Td [(Because of the risk of embr)-17.7 (yo-fetal toxicity)55.3 (,)37.2 ( )36.7 (THALOMID is only a)-9.7 (vailable through)5 ( )]TJ 0.015 Tc 0.207 Tw 0 -1.044 Td [(a restricted program called the )36.6 (THALOMID REMS program )]TJ /T1_1 1 Tf 0.17 Tw [([see W)18.2 (arnings )-37.4 (and)15 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (Precautio)Tj 0.048 Tw (ns \(5.2\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw 0 -1.647 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.007 Tc 0.166 Tw 1.125 0 Td [(P)18.5 (a)-9.5 (t)0.5 (i)0.5 (e)0.5 (nt)0.6 (s m)0.5 (u)0.5 (s)0.5 (t)0.5 ( si)0.5 (g)0.5 (n)0.5 ( a)0.5 ( P)18.5 (a)-9.5 (t)0.5 (i)0.5 (en)0.5 (t)0.5 (-)0.5 (P)0.5 (h)0.5 (y)0.5 (s)0.5 (i)0.5 (ci)0.5 (a)0.5 (n)0.5 ( )36.9 (A)0.5 (g)0.5 (re)0.5 (e)0.5 (m)0.5 (e)0.5 (n)0.5 (t)0.5 ( F)20.5 (o)0.5 (r)0.5 (m)0.5 ( an)0.5 (d)0.5 ( c)0.5 (o)0.5 (m)0.5 (p)0.5 (l)0.5 (y)0.5 ( w)0.5 (i)0.5 (t)0.5 (h)0.5 ( t)0.5 (h)0.5 (e)7 ( )]TJ -0.009 Tc 0.09 Tw 0 -1.062 Td [(requirements to receive )36.7 (THALOMID.)36.8 ( In particular)73.8 (,)36.8 ( females of reproductive potential)-8.9 ( )]TJ 0.021 Tc 0.238 Tw 0 -1.062 Td [(must comply with the pregnanc)20.2 (y testing,)37.2 ( contraception requirements and)21 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.062 Td [(participa)-10.4 (te in monthly telephone sur)-18.5 (veys.)36.5 ( Males must comply with the contraception)-17 ( )]TJ 0.017 Tw 0 -1.062 Td (requirements )Tj /T1_1 1 Tf 0.048 Tw 4.969 0 Td [([see Use in Speci\037c P)18.2 (opula)-9.8 (tions \(8.3\)])]TJ /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw -6.094 -1.512 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.012 Tc 0.076 Tw 1.125 0 Td [(THALOMID is a)-10.3 (vailable only from pharmacies tha)-10.3 (t are certi\036ed in )37 (THALOMID REMS)-11.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(program.)37.2 ( Provide pa)-9.8 (tients with the telephone number and website for informa)-9.7 (tion on)-17 ( )]TJ 0 -1.062 Td [(ho)-9.8 (w to obtain the product.)]TJ -1.125 -1.58 Td [(Pregnanc)20.2 (y Exposure Registr)-17.8 (y)]TJ 0.006 Tc 0.161 Tw 0 -1.539 Td [(I)0.5 (nf)0.5 (o)0.5 (rm)0.5 ( f)0.5 (e)0.5 (ma)0.5 (l)0.5 (es)0.5 ( th)0.5 (e)0.5 (re)0.5 ( i)0.5 (s a)0.5 ( Pr)0.5 (e)0.5 (gn)0.5 (a)0.5 (nc)20.5 (y)0.5 ( E)0.5 (x)0.5 (po)0.5 (s)0.5 (ur)0.5 (e)0.5 ( R)0.5 (e)0.5 (g)0.5 (is)0.5 (tr)-17.5 (y)0.5 ( th)0.5 (a)-9.5 (t)0.5 ( m)0.5 (o)0.5 (n)0.5 (it)0.5 (o)0.5 (rs)0.5 ( pr)0.5 (e)0.5 (gn)0.5 (a)0.5 (n)0.5 (c)20.4 (y)6 ( )]TJ -0.017 Tc 0.04 Tw 0 -1.044 Td [(outcomes in females exposed to )37 (THALOMID during pregnanc)20.2 (y and tha)-9.8 (t they can contact)-17 ( )]TJ 0.002 Tc 0.141 Tw 0 -1.044 Td [(t)0.5 (he)0.5 ( Pr)0.5 (e)0.5 (gna)0.5 (nc)20.5 (y Ex)0.5 (pos)0.5 (ur)0.5 (e Re)0.5 (gi)0.5 (st)0.5 (r)-17.6 (y)0.5 ( b)0.5 (y ca)0.5 (ll)0.5 (in)0.5 (g 1-8)0.5 (88)0.5 (-42)0.5 (3-)0.5 (54)0.5 (36)0.5 ( )]TJ /T1_1 1 Tf [([)0.5 (se)0.5 (e Us)0.5 (e in)0.5 ( S)0.5 (pec)0.5 (i\037)0.5 (c)2 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td [(P)18.2 (opula)-9.7 (tio)]TJ 0.048 Tw (ns \(8.1\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.011 Tw 0 -1.715 Td [(V)18.2 (enous )-36.7 (and Arterial Thromboembolism)]TJ 0 Tc 0.133 Tw 0 -1.539 Td [(Inform pa)-9.9 (tients of the potential risk of developing venous thromboembolism \(such\ )]TJ -0.008 Tc 0.094 Tw 0 -1.044 Td [(as DVT and PE\),)37 ( ischemic heart disease \(inc)20 (luding myocardial infarction\),)37.1 ( and stroke,)29 ( )]TJ -0.009 Tc 0.087 Tw 0 -1.044 Td [(and discuss the need for a)-9.5 (ppropria)-9.6 (te prophylactic trea)-9.6 (tm)0.5 (ent )]TJ /T1_1 1 Tf [([see Boxed )37.3 (W)18.4 (arning a)0.5 (nd)-9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(W)18.2 (arnings and Precautio)]TJ (ns \(5.3\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw 0 -1.715 Td [(Dro)-9.8 (wsiness and Somnolence)]TJ -0.01 Tc 0.085 Tw 0 -1.539 Td [(Inform pa)-10.1 (tients of the risk of dro)-10.2 (wsiness and somnolence with the drug and to a)-10.2 (void)-9.9 ( )]TJ -0.009 Tc 0.089 Tw 0 -1.044 Td [(situa)-9.9 (tions )0.5 (where )0.6 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-88.051 5.241 m -88.051 3.803 l -87.768 5.241 m -87.768 3.803 l -86.352 5.241 m -86.352 3.803 l -92.885 5.241 m -92.885 3.803 l -93.702 5.241 m -93.702 3.803 l -98.196 5.241 m -98.196 3.803 l -160.503 38.285 m -160.503 36.846 l -183.736 74.337 m -183.736 72.899 l -184.274 74.337 m -184.274 72.899 l -184.756 74.337 m -184.756 72.899 l -186.257 75.527 m -186.257 74.088 l -186.71 75.527 m -186.71 74.088 l -189.174 76.207 m -189.174 74.768 l -190.779 77.652 m -190.779 76.214 l -192.863 78.461 m -192.863 77.022 l -193.398 78.461 m -193.398 77.022 l -194.024 78.461 m -194.024 77.022 l -194.263 78.461 m -194.263 77.022 l -196.346 78.461 m -196.346 77.022 l -196.859 78.438 m -196.859 76.999 l -197.064 78.438 m -197.064 76.999 l -194.388 78.461 m -194.388 77.022 l -194.764 78.461 m -194.764 77.022 l -190.762 77.635 m -190.762 76.197 l -191.332 77.635 m -191.332 76.197 l -191.901 77.635 m -191.901 76.197 l S Q BT /T1_1 1 Tf 1.057 Tc -1.057 Tw 7.4099 0 0 8.2332 61.154 547.3508 Tm (01)Tj 0.827 Tc -0.827 Tw 1.957 0 Td (02)Tj 2.57 Tc -2.57 Tw 1.787 0 Td (04)Tj 2.538 Tc -2.538 Tw 3.53 0 Td (06)Tj 2.545 Tc -2.545 Tw 3.498 0 Td (08)Tj 0.802 Tc -0.802 Tw 3.505 0 Td (09)Tj 2.409 Tc -2.409 Tw 1.762 0 Td (01)Tj -0.08 Tc 0.08 Tw 3.249 0 Td (10)Tj -0.1 Tc 0.1 Tw 4.87 0 Td (14)Tj 0.414 Tc -0.414 Tw 0.86 0 Td (01)Tj 0 Tc 0 Tw 1.274 0 Td (50)Tj -0.1 Tc 0.1 Tw 1.371 0 Td (16)Tj 0 Tc 0 Tw 0.86 0 Td (0)Tj -30.18 1.562 Td (0.0)Tj ET 59.507 562.682 1.767 0.134 re f 0.296 w 2 J 61.274 562.682 -1.767 0.134 re S BT 7.4099 0 0 8.2332 48.8769 575.5865 Tm (0.1)Tj ET 59.507 578.058 1.767 0.131 re f 61.274 578.058 -1.767 0.132 re S BT 7.4099 0 0 8.2332 48.8769 590.964 Tm (0.2)Tj ET 59.507 593.436 1.767 0.135 re f 61.274 593.436 -1.767 0.134 re S BT 7.4099 0 0 8.2332 48.8769 606.341 Tm (0.3)Tj ET 59.507 608.81 1.767 0.134 re f 61.274 608.81 -1.767 0.134 re S 60.323 605.735 0.95 0.134 re f 61.274 605.735 -0.95 0.134 re S 60.323 602.66 0.95 0.135 re f 61.274 602.66 -0.95 0.134 re S 60.323 599.585 0.95 0.135 re f 61.274 599.586 -0.95 0.134 re S 60.323 596.511 0.95 0.134 re f 61.274 596.511 -0.95 0.134 re S 60.323 621.115 0.95 0.134 re f 61.274 621.115 -0.95 0.134 re S 60.323 618.039 0.95 0.134 re f 61.274 618.039 -0.95 0.134 re S 60.323 614.963 0.95 0.133 re f 61.274 614.963 -0.95 0.134 re S 60.323 611.886 0.95 0.135 re f 61.274 611.886 -0.95 0.134 re S 60.323 636.49 0.95 0.134 re f 61.274 636.49 -0.95 0.134 re S 60.323 633.415 0.95 0.134 re f 61.274 633.415 -0.95 0.134 re S 60.323 630.341 0.95 0.134 re f 61.274 630.341 -0.95 0.134 re S 60.323 627.266 0.95 0.135 re f 61.274 627.266 -0.95 0.134 re S 60.323 651.867 0.95 0.134 re f 61.274 651.867 -0.95 0.134 re S 60.323 648.791 0.95 0.134 re f 61.274 648.791 -0.95 0.134 re S 60.323 645.716 0.95 0.134 re f 61.274 645.716 -0.95 0.134 re S 60.323 642.64 0.95 0.135 re f 61.274 642.64 -0.95 0.134 re S 60.323 667.244 0.95 0.134 re f 61.274 667.244 -0.95 0.134 re S 60.323 664.168 0.95 0.134 re f 61.274 664.169 -0.95 0.134 re S 60.323 661.093 0.95 0.134 re f 61.274 661.093 -0.95 0.134 re S 60.323 658.018 0.95 0.134 re f 61.274 658.018 -0.95 0.134 re S 60.323 682.626 0.95 0.134 re f 61.274 682.626 -0.95 0.134 re S 60.323 679.549 0.95 0.134 re f 61.274 679.549 -0.95 0.134 re S 60.323 676.472 0.95 0.134 re f 61.274 676.472 -0.95 0.134 re S 60.323 673.395 0.95 0.135 re f 61.274 673.395 -0.95 0.134 re S 60.323 697.992 0.95 0.134 re f 61.274 697.992 -0.95 0.134 re S 60.323 694.92 0.95 0.134 re f 61.274 694.92 -0.95 0.134 re S 60.323 691.847 0.95 0.135 re f 61.274 691.847 -0.95 0.134 re S 60.323 688.774 0.95 0.134 re f 61.274 688.775 -0.95 0.134 re S 60.323 713.375 0.95 0.135 re f 61.274 713.375 -0.95 0.134 re S 60.323 710.298 0.95 0.134 re f 61.274 710.298 -0.95 0.134 re S 60.323 707.22 0.95 0.134 re f 61.274 707.22 -0.95 0.134 re S 60.323 704.143 0.95 0.134 re f 61.274 704.143 -0.95 0.134 re S 60.323 590.36 0.95 0.134 re f 61.274 590.36 -0.95 0.134 re S 60.323 587.285 0.95 0.133 re f 61.274 587.285 -0.95 0.134 re S 60.323 584.209 0.95 0.134 re f 61.274 584.209 -0.95 0.134 re S 60.323 581.133 0.95 0.134 re f 61.274 581.133 -0.95 0.134 re S 60.323 574.981 0.95 0.134 re f 61.274 574.981 -0.95 0.134 re S 60.323 571.907 0.95 0.134 re f 61.274 571.907 -0.95 0.134 re S 60.323 568.831 0.95 0.134 re f 61.274 568.832 -0.95 0.134 re S 60.323 565.757 0.95 0.134 re f 61.274 565.757 -0.95 0.134 re S BT /T1_2 1 Tf 7.4099 0 0 8.2332 48.8769 621.7185 Tm (0.4)Tj ET 59.507 624.191 1.767 0.135 re f 61.274 624.192 -1.767 0.135 re S BT 7.4099 0 0 8.2332 48.8769 637.0955 Tm (0.5)Tj ET 59.507 639.564 1.767 0.134 re f 61.274 639.564 -1.767 0.134 re S BT 7.4099 0 0 8.2332 48.8769 652.4725 Tm (0.6)Tj ET 59.507 654.943 1.767 0.132 re f 61.274 654.943 -1.767 0.133 re S BT 7.4099 0 0 8.2332 48.8769 667.85 Tm (0.7)Tj ET 59.507 670.319 1.767 0.133 re f 61.274 670.319 -1.767 0.134 re S BT 7.4099 0 0 8.2332 48.8769 683.2271 Tm (0.8)Tj ET 59.507 685.702 1.767 0.135 re f 61.274 685.702 -1.767 0.135 re S BT 7.4099 0 0 8.2332 48.8769 698.6042 Tm (0.9)Tj ET 59.507 701.065 1.767 0.134 re f 61.274 701.065 -1.767 0.134 re S q 36 511.755 249.384 209.428 re W n BT 7.4099 0 0 8.2332 48.8339 713.9814 Tm (1.0)Tj ET Q 59.576 716.453 1.698 0.134 re f 61.274 716.453 -1.699 0.134 re S q 36 513.828 249.384 207.355 re W n 0.593 w 284.878 561.196 -223.604 159.691 re S Q 75.808 556.648 0.133 4.547 re f 0.593 w 75.941 556.649 -0.133 4.546 re S 88.827 556.648 0.133 4.547 re f 88.961 556.649 -0.133 4.546 re S BT 7.4099 0 0 8.2332 98.357 547.3508 Tm (30)Tj ET 101.847 556.648 0.133 4.547 re f 101.98 556.649 -0.133 4.546 re S 114.982 556.648 0.133 4.547 re f 115.116 556.649 -0.133 4.546 re S BT 7.4099 0 0 8.2332 124.399 547.3508 Tm (50)Tj ET 127.889 556.648 0.133 4.547 re f 128.023 556.649 -0.133 4.546 re S 140.905 556.648 0.133 4.547 re f 141.038 556.649 -0.133 4.546 re S BT 7.4099 0 0 8.2332 150.4344 547.3508 Tm (70)Tj ET 153.924 556.648 0.134 4.547 re f 154.058 556.649 -0.133 4.546 re S 166.879 556.648 0.133 4.547 re f 167.012 556.649 -0.133 4.546 re S 179.936 556.648 0.133 4.547 re f 180.069 556.649 -0.133 4.546 re S BT -0.08 Tc 0.08 Tw 7.4099 0 0 8.2332 188.0111 547.3508 Tm (10)Tj 0 Tc 0 Tw 0.88 0 Td (0)Tj ET 192.982 556.648 0.134 4.547 re f 193.116 556.649 -0.133 4.546 re S 245.06 556.648 0.133 4.547 re f 245.194 556.649 -0.133 4.546 re S 205.935 556.648 0.133 4.547 re f 206.069 556.649 -0.133 4.546 re S BT -0.12 Tc 0.12 Tw 7.4099 0 0 8.2332 214.331 547.3508 Tm (12)Tj 0 Tc 0 Tw 0.84 0 Td (0)Tj ET 219.155 556.648 0.132 4.547 re f 219.288 556.649 -0.133 4.546 re S BT -0.12 Tc 0.12 Tw 7.4099 0 0 8.2332 227.3281 547.3508 Tm (13)Tj 0 Tc 0 Tw 0.84 0 Td (0)Tj ET 232.151 556.648 0.133 4.547 re f 232.285 556.649 -0.133 4.546 re S 271.099 556.648 0.133 4.547 re f 271.233 556.649 -0.133 4.546 re S 258.122 556.648 0.133 4.547 re f 258.255 556.649 -0.133 4.546 re S 62.932 556.65 0.133 4.546 re f 0 J 63.066 556.65 -0.133 4.546 re S q 36 511.755 249.384 209.428 re W n BT -0.005 Tc 0 8.2332 -8.2332 0 42.8337 576.5776 Tm (Proportion of Subjects )Tj 8.231 0 Td (With No Progression)Tj ET Q 0.261 G 1.029 w 1 j 2 J [5.146 2.573]0 d q 1 0 0 1 167.5445 521.4009 cm 0 0 m 20.692 0 l S Q BT -0.01 Tc 0.01 Tw 8.2332 0 0 8.2332 192.6268 517.9929 Tm (Placebo/Dex)Tj ET 0 G 0 j 0 J []0 d q 1 0 0 1 108.5188 521.4009 cm 0 0 m 20.691 0 l S Q BT 8.2332 0 0 8.2332 133.6012 517.9929 Tm (Thal/Dex)Tj 0 Tc 0 Tw -9.836 0 Td (T)Tj -0.01 Tc 0.379 0 Td (reatment Group )Tj 0 Tc 11.957 2.202 Td (T)Tj -0.01 Tc 0.435 0 Td (ime \(weeks\))Tj 0.01 Tw 11.537 -2.202 Td (Censored)Tj ET 1 j 2 J q 1 0 0 1 235.8165 524.2244 cm 0 0 m 0 -2.87 l 5.439 0 m 5.439 -2.87 l 10.877 0 m 10.877 -2.87 l S Q q 36 513.828 249.384 207.355 re W n 0.515 w 0 j 0 J 285.127 514.086 -235.961 13.77 re S Q BT /GS1 gs /T1_0 1 Tf -0.018 Tc 0.036 Tw 8 0 0 8 36 499.2507 Tm [(KEY)36.9 (: Placebo/De)10 (x=placebo/de)10 (xamethasone; Thal/De)10 (x=THALOMID/de)9.9 (xamethasone)]TJ -0.017 Tc 0.017 Tw 0 -2.551 Td (14.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Er)-17.8 (ythema Nodosum Leprosum \(ENL\))]TJ /T1_3 1 Tf -0.004 Tc 0.117 Tw -3.375 -1.587 Td [(The primar)-18.4 (y )0.5 (da)-10.4 (ta )0.5 (demonstra)-10.4 (ting )0.5 (the ef\036cac)19.6 (y of )0.5 (thalidomide )0.5 (in )0.5 (the )0.5 (trea)-10.4 (tment of the)-4 ( )]TJ -0.008 Tc 0.095 Tw 0 -1.047 Td [(cutaneous manifesta)-10.2 (tions of modera)-10.1 (te to severe ENL are derived from the published)-8 ( )]TJ 0.096 Tw 0 -1.047 Td [(medical litera)-10.4 (ture and from a retrospective stud)-10.3 (y of 102 pa)-10.3 (tients trea)-10.3 (ted by the U.S.)29 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.047 Td [(Public Health Ser)-17.8 (vice.)]TJ -0.01 Tc 0.082 Tw 0 -1.722 Td [(T)74.4 (w)0.5 (o )0.5 (d)0.5 (oubl)0.5 (e-)0.5 (bli)0.5 (nd,)37.4 ( )0.6 (ra)0.5 (ndo)0.5 (miz)0.5 (ed,)37.5 ( )0.5 (co)0.5 (ntr)0.5 (ol)0.5 (led )0.6 (tr)0.5 (ial)0.5 (s )0.5 (r)0.5 (epo)0.5 (rt)0.5 (ed )0.6 (the)0.5 ( )0.5 (d)0.5 (erm)0.5 (a)-9.6 (t)0.5 (olo)0.5 (gic)0.5 ( )0.5 (re)0.5 (spo)0.5 (nse)0.5 ( )0.5 (t)0.5 (o)-10 ( )]TJ -0.013 Tc 0.071 Tw 0 -1.047 Td [(a 7-day course of 100 mg thalidomide \(four times daily\) or control.)36.7 ( Dosa)-10.3 (ge was lo)-10.3 (wer)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.047 Td [(for pa)-9.8 (tients under 50 kg in weight.)]TJ ET 0.5 w 0 j 0 J /GS2 gs q 1 0 0 1 137.34 360.485 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 187.56 360.485 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 36 323.9831 cm 0 0 m 51.12 0 l S Q q 1 0 0 1 137.34 323.9831 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 237.6 323.9831 cm 0 0 m 50.4 0 l S Q q 1 0 0 1 87.12 360.235 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 137.34 360.235 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 187.56 360.235 cm 0 0 m 50.04 0 l S Q q 1 0 0 1 237.6 360.235 cm 0 0 m 50.4 0 l S Q q 1 0 0 1 87.12 324.2331 cm 0 0 m 0 35.752 l S Q q 1 0 0 1 137.34 324.2331 cm 0 0 m 0 35.752 l S Q q 1 0 0 1 87.12 323.9831 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 87.12 296.7312 cm 0 0 m 0 27.002 l S Q q 1 0 0 1 137.34 296.7312 cm 0 0 m 0 27.002 l S Q q 1 0 0 1 187.56 324.2331 cm 0 0 m 0 35.752 l S Q q 1 0 0 1 237.6 324.2331 cm 0 0 m 0 35.752 l S Q q 1 0 0 1 187.56 323.9831 cm 0 0 m 50.04 0 l S Q q 1 0 0 1 187.56 296.7312 cm 0 0 m 0 27.002 l S Q q 1 0 0 1 237.6 296.7312 cm 0 0 m 0 27.002 l S Q q 1 0 0 1 87.12 360.485 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 36 360.235 cm 0 0 m 51.12 0 l S Q 1 w q 1 0 0 1 36 296.2312 cm 0 0 m 51.12 0 l S Q q 1 0 0 1 87.12 296.2312 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 137.34 296.2312 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 187.56 296.2312 cm 0 0 m 50.04 0 l S Q q 1 0 0 1 237.6 296.2312 cm 0 0 m 50.4 0 l S Q 0.5 w q 1 0 0 1 36 266.3193 cm 0 0 m 51.12 0 l S Q q 1 0 0 1 87.12 266.3193 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 137.34 266.3193 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 187.56 266.3193 cm 0 0 m 50.04 0 l S Q q 1 0 0 1 237.6 266.3193 cm 0 0 m 50.4 0 l S Q 1 w q 1 0 0 1 36 381.6469 cm 0 0 m 51.12 0 l S Q q 1 0 0 1 87.12 381.6469 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 137.34 381.6469 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 187.56 381.6469 cm 0 0 m 50.04 0 l S Q q 1 0 0 1 237.6 381.6469 cm 0 0 m 50.4 0 l S Q BT /GS1 gs /T1_0 1 Tf -0.022 Tc 0.035 Tw 8 0 0 8 36 393.7469 Tm [(T)69.2 (a)-4.8 (b)-4.8 (l)-4.8 (e)-4.8 ( )-17.8 (1)-4.8 (0)-4.8 (:)]TJ /Span<>> BDC 3.423 0 Td ( )Tj EMC 1.577 0 Td [(Double-Blind,)37.3 ( Controlled Clinical T)74.2 (rials of Thalidomide in P)24.2 (atients with)-22 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td (ENL: Cutaneous Response)Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 36 363.835 Tm (Reference)Tj 0.048 Tw 7.204 0 Td [(No.)37.2 ( of P)24.2 (atients)]TJ 6.737 1.062 Td [(No.)37.2 ( T)74.2 (reatment)]TJ 0 Tc 0 Tw 7.6 0 0 8 182.9492 372.335 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 149.129 363.835 Tm (Courses*)Tj 0.048 Tw 7.415 0 Td [(P)24.2 (ercent Responding**)]TJ /T1_3 1 Tf 0.012 Tw -22.3 -1.479 Td (Iyer )Tj /T1_4 1 Tf 0.048 Tw 1.577 0 Td (et al.)Tj /T1_3 1 Tf 0.011 Tw -1.577 -1.062 Td [(Bull W)18.2 (orld )-36.8 (Health)-11.9 ( )]TJ 0.012 Tw 0 -1.062 Td [(Organiza)-9.8 (tion)-12 ( )]TJ 0 -1.062 Td (1971;45:719)Tj 9.556 1.594 Td (92)Tj 6.374 0 Td (204)Tj 5.106 0.531 Td (Thalidomide)Tj 0 Tc 0 Tw 7.6 0 0 8 229.2844 343.5031 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 206.1406 335.0031 Tm (75%)Tj 6.24 1.062 Td (Aspirin)Tj 0 Tc 0 Tw 7.6 0 0 8 272.2873 343.5031 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 256.4856 335.0031 Tm (25%)Tj -29.011 -2.406 Td (Sheskin )Tj /T1_4 1 Tf 0.048 Tw 3.115 0 Td (et al.)Tj /T1_3 1 Tf -3.115 -1.062 Td [(Int J Lep)-11.9 ( )]TJ 0.012 Tw 0 -1.062 Td (1969;37:135)Tj 9.556 1.062 Td (52)Tj 6.374 0 Td (173)Tj 5.106 0.531 Td (Thalidomide)Tj 0 Tc 0 Tw 7.6 0 0 8 229.2844 311.5012 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 206.1406 303.0012 Tm (66%)Tj 6.055 1.062 Td (Placebo)Tj 0 Tc 0 Tw 7.6 0 0 8 273.6894 311.5012 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 256.4856 303.0012 Tm (10%)Tj 0.048 Tw -29.011 -2.01 Td (*)Tj /Span<>> BDC ( )Tj EMC 0.789 0 Td [(In pa)-9.8 (tients with cutaneous lesions)]TJ -0.789 -1.062 Td (**)Tj /Span<>> BDC ( )Tj EMC 0.789 0 Td [(Iyer:)37.2 ( Complete response or lesions absent)]TJ -0.789 -1.062 Td (**)Tj /Span<>> BDC ( )Tj EMC 0.789 0 Td [(Sheskin:)37.2 ( Complete improvement + )37.2 (\223striking\224)37.2 ( improvement \(i.e.,)37.2 ( >50% improvement\))]TJ -0.005 Tc 0.107 Tw 8 0 0 8 36 249.8146 Tm [(W)18.3 (a)-9.7 (ters reported the results of two studies,)37.3 ( both double-blind,)37.3 ( randomized,)37.2 ( placebo-)]TJ -0.015 Tc 0.061 Tw 0 -1.047 Td [(controlled,)36.6 ( crossover trials in a total of 10 hospitalized,)36.6 ( steroid-dependent pa)-10.3 (tients with)-15 ( )]TJ -0.017 Tc 0.058 Tw 0 -1.047 Td [(chronic ENL trea)-9.8 (ted with 100 mg thalidomide or placebo \(three times daily\).)37.2 ( )36.7 (All pa)-9.8 (tients)-17 ( )]TJ 0.048 Tw 0 -1.047 Td [(also received da)-9.8 (psone.)37.2 ( )37.2 (The primar)-17.7 (y endpoint was reduction in weekly steroid dosa)-9.7 (ge.)]TJ ET 0.5 w /GS2 gs q 1 0 0 1 187.56 169.9003 cm 0 0 m 0 12.412 l S Q q 1 0 0 1 237.78 169.9003 cm 0 0 m 0 12.412 l S Q q 1 0 0 1 36 158.8983 cm 0 0 m 51.12 0 l S Q q 1 0 0 1 137.34 158.8983 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 237.78 158.8983 cm 0 0 m 50.22 0 l S Q q 1 0 0 1 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of the cutaneous manifesta)-10 (tions of modera)-9.9 (te to severe)-12 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.047 Td (ENL with thalidomide.)Tj ET q 1 0 0 1 324 315.0971 cm 0 0 m 60.639 0 l S Q BT /T1_0 1 Tf 0.017 Tw 8 0 0 8 324 727.248 Tm (15)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (REFERENCES)Tj /T1_3 1 Tf -0.01 Tc 0.086 Tw -3.375 -1.815 Td [(1)7.2 (.)]TJ /Span<>> BDC 0.649 0 Td ( )Tj EMC 0.476 0 Td [(OSHA Hazardous Drugs.)36.7 ( OSHA [Accessed on 02 July 2014,)36.7 ( from http://www)36.7 (.osha.)]TJ -0.017 Tc 0.017 Tw 0 -1.14 Td [(gov/SL)94.3 (TC/hazardousdrugs/index.html].)]TJ /T1_0 1 Tf -1.125 -2.144 Td (16)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (HOW SUPPLIED/STORAGE AND HANDLING)Tj -0.014 Tc 0.063 Tw -3.375 -2.036 Td [(\(THIS PRODUCT IS ONL)92.2 (Y SUPPLIED )0.5 (TO PHARMACIES CER)18.2 (TIFIED IN THE THALOMID)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.159 Td [(REMS PROGRAM - See BOXED W)18.2 (ARNING\))]TJ 0.017 Tw 0 -1.744 Td (16.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (How Supplied)Tj /T1_3 1 Tf 0.004 Tc 0.156 Tw -3.375 -1.68 Td [(50 mg ca)-10.4 (psules [white opaque],)36.5 ( imprinted )36.6 (\223Celgene/50 mg\224)36.6 ( with a )36.5 (\223Do Not Get)4 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.14 Td [(Pregnant\224)37.2 ( logo.)]TJ 0 -1.32 Td [(Individual blister packs of 1 ca)-9.8 (psule \(NDC 59572-205-17\).)]TJ 0 -1.32 Td [(Individual blister packs of 28 ca)-9.8 (psules \(NDC 59572-205-14\).)]TJ 0.043 Tw 0 -1.86 Td [(100 mg ca)-9.8 (psules [tan],)37.2 ( imprinted )37.3 (\223Celgene/100 mg\224)37.2 ( with a )37.2 (\223Do Not Get Pregnant\224)37.2 ( logo.)20 ( )]TJ 0.048 Tw 0 -1.32 Td [(Individual blister packs of 28 ca)-9.8 (psules \(NDC 59572-210-15\).)]TJ -0.001 Tc 0.13 Tw 0 -1.86 Td [(150 mg ca)-10.1 (psules [tan and blue],)36.8 ( imprinted )36.8 (\223Celgene/150 mg\224)36.8 ( with a )36.9 (\223Do Not Get)-1 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.14 Td [(Pregnant\224)37.2 ( logo.)]TJ 0 -1.32 Td [(Individual blister packs of 28 ca)-9.8 (psules \(NDC 59572-215-13\).)]TJ -0.021 Tc 0.036 Tw 0 -1.86 Td [(200 mg ca)-10.2 (psules [blue],)36.8 ( imprinted )36.8 (\223Celgene/200 mg\224)36.8 ( with a )36.8 (\223Do Not Get Pregnant\224)36.8 ( logo.)16 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.32 Td [(Individual blister packs of 28 ca)-9.8 (psules \(NDC 59572-220-16\).)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.969 Td (16.2)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Storage)Tj /T1_3 1 Tf 0.048 Tw -3.375 -1.68 Td [(This drug must not be repacka)-9.8 (ged.)]TJ 0.04 Tw 0 -1.86 Td [(Store a)-9.8 (t 20\260C-25\260C \(68\260F-77\260F\); excursions permitted to 15-30\272\ C \(59-86\272 F\).)37.2 ( )]TJ [([See USP)-16.9 ( )]TJ 0.011 Tw 0 -1.14 Td [(Controlled )-36.8 (Room T)74.2 (empera)-9.8 (ture])]TJ 0.048 Tw [(.)37.2 ( Protect from light.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.969 Td (16.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Handling and Disposal)Tj /T1_3 1 Tf -0.005 Tc 0.108 Tw -3.375 -1.68 Td [(Care should be exercised in handling of )36.6 (THALOMID.)37.1 ( )36.6 (THALOMID ca)-9.8 (psules 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ca)-9.8 (p.)]TJ 0.017 Tw -1.125 -1.609 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.007 Tc 0.1 Tw 1.125 0 Td [(Instruct pa)-10.2 (tient to immedia)-10.1 (tely stop taking )36.9 (THALOMID and contact her healthcare)-6.9 ( )]TJ -0.017 Tc 0.039 Tw 0 -1.159 Td [(provider if she becomes pregnant while taking this drug,)37.2 ( if she misses her menstrual)-17 ( )]TJ -0.013 Tc 0.067 Tw 0 -1.159 Td [(period,)37.3 ( or experiences unusual menstrual bleeding,)37.3 ( if she stops taking birth control,)24 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.159 Td [(or if she thinks FOR )37.2 (ANY REASON tha)-9.8 (t she may be pregnant.)]TJ 0.017 Tw -1.125 -1.609 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.039 Tw 1.125 0 Td [(Advise pa)-9.8 (tient tha)-9.8 (t if her healthcare provider is not a)-9.7 (vailable,)37.2 ( she should call Celgene)-17 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.159 Td [(Customer )0.5 (Care )0.5 (Center a)-9.7 (t 1-888-423-5436 )]TJ /T1_4 1 Tf 15.689 0 Td [([see )37.5 (W)18.2 (arnings )0.5 (and )0.5 (Precautions )0.5 (\(5.1\) )0.5 (and)-14 ( )]TJ -0.017 Tc 0.048 Tw -15.689 -1.159 Td [(Use in Speci\037c P)18.2 (opula)-9.8 (tions \(8.1\)])]TJ /T1_3 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw -1.125 -1.609 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.012 Tc 0.074 Tw 1.125 0 Td [(Advise males to al)-10 (ways use a la)-10.1 (tex or synthetic condom during an)-10.1 (y sexual contact)-12 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.159 Td [(with females of reproductive potential while taking )37.2 (THALOMID and for up to 4 weeks)-17 ( )]TJ 0 -1.159 Td [(after discontinuing )37.2 (THALOMID,)37.2 ( even if they ha)-9.8 (ve undergone a successful vasectomy)55.2 (.)]TJ 0.017 Tw -1.125 -1.609 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.003 Tc 0.151 Tw 1.125 0 Td [(Advise male pa)-10.4 (tients taking )36.7 (THALOMID tha)-10.3 (t they must not dona)-10.3 (te sperm )]TJ /T1_4 1 Tf -0.003 Tw [([see)3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.159 Td [(W)18.2 (arnings and Precautions \(5.1\) and Use in Speci\037c P)18.2 (opula)-9.8 (tions \(8.3\)])]TJ /T1_3 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Demographics)]TJ -0.012 Tc 0.012 Tw 7.6 0 0 8 36 684.4242 Tm (Characteristic)Tj 0.048 Tw 11.857 3.739 Td (Study 1)Tj 13.232 0 Td (Study 2)Tj 0.012 Tw -17.268 -1.614 Td (THALOMID/)Tj -0.896 -1.062 Td [(De)10.2 (xamethasone)-12 ( )]TJ 1.538 -1.062 Td (\(N=103\))Tj 5.07 1.062 Td [(De)10.2 (xamethasone)]TJ 1.538 -1.062 Td (\(N=104\))Tj 5.966 2.125 Td (THALOMID/)Tj -0.896 -1.062 Td [(De)10.2 (xamethasone)-12 ( )]TJ 1.538 -1.062 Td (\(N=235\))Tj 6.494 2.125 Td (Placebo/)Tj -1.408 -1.062 Td [(De)10.2 (xamethasone)-12 ( )]TJ 1.538 -1.062 Td (\(N=235\))Tj 0.048 Tw -28.304 -1.479 Td (Age \(years\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC (Median)Tj 0.012 Tw 9.556 0 Td (65)Tj 6.608 0 Td (68)Tj 6.608 0 Td (65)Tj 6.624 0 Td (66)Tj 0.364 Tw /Span<>> BDC -29.396 -1.344 Td ( )Tj EMC (Range)Tj -0.115 Tw 8.806 0 Td (37)Tj /Span<>> BDC ( )Tj EMC (-)Tj /Span<>> BDC ( )Tj EMC (83)Tj 6.608 0 Td (38)Tj /Span<>> BDC ( )Tj EMC (-)Tj /Span<>> BDC ( )Tj EMC (83)Tj 6.608 0 Td (39)Tj /Span<>> BDC ( )Tj EMC (-)Tj /Span<>> BDC ( )Tj EMC (86)Tj 6.624 0 Td (31)Tj /Span<>> BDC ( )Tj EMC (-)Tj /Span<>> BDC ( )Tj EMC (84)Tj /T1_0 1 Tf 0.012 Tw -28.646 -1.344 Td (Gender)Tj 0 Tc 0 Tw 5.32 0 0 5.6 56.8376 643.0005 Tm (1)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 59.3262 640.3365 Tm [(,)37.2 ( N \(%\))]TJ /T1_1 1 Tf 0.364 Tw /Span<>> BDC -3.069 -1.344 Td ( )Tj EMC (Male)Tj 0.048 Tw 8.722 0 Td (53 \(51\))Tj 6.608 0 Td (61 \(59\))Tj 6.374 0 Td (118 \(50\))Tj 6.624 0 Td (120 \(51\))Tj 0.364 Tw /Span<>> BDC -28.328 -1.344 Td ( )Tj EMC [(F)24.2 (emale)]TJ 0.048 Tw 8.722 0 Td (50 \(49\))Tj 6.608 0 Td (42 \(40\))Tj 6.374 0 Td (117 \(50\))Tj 6.624 0 Td (115 \(49\))Tj /T1_0 1 Tf 0.012 Tw -28.328 -1.344 Td (Race)Tj 0 Tc 0 Tw 5.32 0 0 5.6 50.5478 610.7448 Tm (2)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 53.0364 608.0808 Tm [(,)37.2 ( N \(%\))]TJ /T1_1 1 Tf 0.364 Tw /Span<>> BDC -2.242 -1.344 Td ( )Tj EMC (Caucasian)Tj 0.048 Tw 8.722 0 Td (90 \(87\))Tj 6.608 0 Td (90 \(87\))Tj 6.374 0 Td (224 \(95\))Tj 6.624 0 Td (221 \(94\))Tj 0.364 Tw /Span<>> BDC -28.328 -1.344 Td ( )Tj EMC (Black)Tj 0.048 Tw 8.722 0 Td (11 \(11\))Tj 6.608 0 Td (11 \(11\))Tj 7.076 0 Td (7 \(3\))Tj 6.39 0 Td (10 \(4\))Tj 0.364 Tw /Span<>> BDC -28.796 -1.344 Td ( )Tj EMC (Other)Tj 0.048 Tw 9.19 0 Td (1 \(1\))Tj 6.608 0 Td (2 \(2\))Tj 6.446 0 Td (4 \(2\))Tj 0 Tc 0 Tw 5.32 0 0 5.6 217.7353 578.4891 Tm (3)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 255.3961 575.8251 Tm (4 \(2\))Tj 0 Tc 0 Tw 5.32 0 0 5.6 268.0803 578.4891 Tm (4)Tj -0.012 Tc 0.012 Tw -43.624 -2.113 Td (1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 563.9932 Tm [(Missing informa)-9.8 (tion in Stud)-9.8 (y 1 for 1 pa)-9.7 (tient in the Dex alone group)]TJ 0.012 Tw 5.32 0 0 5.6 36 558.1572 Tm (2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 555.4932 Tm [(Missing informa)-9.8 (tion in Stud)-9.8 (y 1 for 1 pa)-9.7 (tient per arm)]TJ 0.012 Tw 5.32 0 0 5.6 36 549.6572 Tm (3)Tj /Span<>> BDC ( )Tj EMC 0.04 Tw 7.6 0 0 8 41 546.9932 Tm [(Black/Hispanic [1 \(0.4%\)],)37.2 ( Hispanic [2 \(0.9%\)],)37.2 ( Hispanic/White [1 \(0.4%\)],)37.2 ( Other [0 \(0.0%\)])]TJ 0.012 Tw 5.32 0 0 5.6 36 541.1572 Tm (4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 538.4932 Tm [(Hispanic [1 \(0.4%\)],)37.2 ( )37.2 (Asian/P)18.2 (acific Islander [2 \(0.9%\)],)37.2 ( Other [1 \(0.4%\)])]TJ ET /GS1 gs q 1 0 0 1 117 460.6655 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 460.6655 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 460.4155 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 460.4155 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 449.9136 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 460.4155 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 449.9136 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 449.6636 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 449.6636 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 439.1617 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 449.6636 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 439.1617 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 438.9117 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 438.9117 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 438.9117 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 36 428.1598 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 428.1598 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 417.6579 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 428.1598 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 417.6579 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 417.4079 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 417.4079 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 406.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 417.4079 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 406.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 406.6559 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 406.6559 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 396.1541 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 406.6559 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 396.1541 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 395.9041 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 395.9041 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 385.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 395.9041 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 385.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 385.1521 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 385.1521 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 385.1521 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 36 374.4002 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 374.4002 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 363.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 374.4002 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 363.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 363.6483 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 363.6483 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 353.1464 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 363.6483 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 353.1464 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 352.8964 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 352.8964 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 342.3945 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 352.8964 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 342.3945 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 342.1445 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 342.1445 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 342.1445 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 36 331.3926 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 331.3926 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 320.8907 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 207.36 331.3926 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 320.8907 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 320.6407 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 320.6407 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 117 310.3887 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 207.36 320.6407 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 207.36 310.3887 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 36 271.4768 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 271.4768 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 271.4768 cm 0 0 m 80.64 0 l S Q 1 w q 1 0 0 1 36 309.8887 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 309.8887 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 309.8887 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 36 503.3313 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 503.3313 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 503.3313 cm 0 0 m 80.64 0 l S Q 0.5 w q 1 0 0 1 117 482.1694 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 207.36 482.1694 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 36 481.9194 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 481.9194 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 481.9194 cm 0 0 m 80.64 0 l S Q q 1 0 0 1 36 471.1674 cm 0 0 m 81 0 l S Q q 1 0 0 1 117 471.1674 cm 0 0 m 90.36 0 l S Q q 1 0 0 1 207.36 471.1674 cm 0 0 m 80.64 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.017 Tc 8 0 0 8 36 506.9313 Tm [(T)74.2 (able 7:)]TJ /Span<>> BDC ( )Tj EMC 5 0 Td (Baseline Disease Characteristics \(Study 1\))Tj -0.012 Tc 7.6 0 0 8 36 485.5193 Tm (Disease Characteristic)Tj 0.012 Tw 11.296 1.062 Td [(THALOMID/De)10.2 (xamethasone)]TJ 0 Tc 0 Tw 7.6 0 0 8 202.5119 494.0193 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 150.2756 485.5193 Tm (\(N=103\))Tj 0.048 Tw 8.539 1.062 Td [(De)10.2 (xamethasone alone)]TJ 0 Tc 0 Tw 7.6 0 0 8 280.4366 494.0193 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 235.9006 485.5193 Tm (\(N=104\))Tj 0.048 Tw -26.303 -1.479 Td [(Stage \(Durie-Salmon\),)37.2 ( N \(%\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 119.5271 476.3514 Tm (1)Tj /T1_1 1 Tf 0.352 Tw /Span<>> BDC 7.6 0 0 8 36 462.9355 Tm ( )Tj EMC (I)Tj -0.012 Tc 0.048 Tw 14.573 0 Td (14 \(13.6%\))Tj 11.266 0 Td (17 \(16.3%\))Tj 0.364 Tw /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC (II)Tj 0.048 Tw 14.573 0 Td (47 \(45.6%\))Tj 11.266 0 Td (44 \(42.3%\))Tj 0.364 Tw /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC (III)Tj 0.048 Tw 14.573 0 Td (41 \(39.8%\))Tj 11.266 0 Td (43 \(41.3%\))Tj /T1_0 1 Tf -25.84 -1.344 Td [(Immunoglobulin T)55.2 (ype,)37.2 ( N \(%\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 119.4454 433.3438 Tm (2)Tj /T1_1 1 Tf -0.012 Tc 0.364 Tw /Span<>> BDC 7.6 0 0 8 36 419.9279 Tm ( )Tj EMC (IgA)Tj 0.048 Tw 14.573 0 Td (21 \(20.4%\))Tj 11.266 0 Td (22 \(21.2%\))Tj 0.364 Tw /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC (IgG)Tj 0.048 Tw 14.573 0 Td (63 \(61.2%\))Tj 11.266 0 Td (60 \(57.7%\))Tj 0.364 Tw /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC (IgM)Tj 0.048 Tw 15.041 0 Td (0 \(0.0%\))Tj 11.266 0 Td (1 \(1.0%\))Tj 0.364 Tw /Span<>> BDC -26.307 -1.344 Td ( )Tj EMC [(Bic)20.2 (lonal)]TJ 0.048 Tw 15.041 0 Td (0 \(0.0%\))Tj 11.266 0 Td (1 \(1.0%\))Tj /T1_0 1 Tf -26.307 -1.344 Td [(L)37.2 (ytic Lesions)]TJ 0 Tc 0 Tw 5.32 0 0 5.6 74.2455 379.5842 Tm (3)Tj /T1_1 1 Tf -0.012 Tc 0.364 Tw /Span<>> BDC 7.6 0 0 8 36 366.1683 Tm ( )Tj EMC (None)Tj 0.048 Tw 14.573 0 Td (28 \(27.1%\))Tj 11.266 0 Td (14 \(13.5%\))Tj /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC 0.592 0 Td (1-3 lesions)Tj 13.981 0 Td (24 \(23.3%\))Tj 11.266 0 Td (19 \(18.3%\))Tj /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC 0.592 0 Td [(>3 lesions)-11.9 ( )]TJ 13.981 0 Td (34 \(33.0%\))Tj 11.266 0 Td (41 \(39.4%\))Tj /T1_0 1 Tf -25.84 -1.344 Td (Serum Light Chain)Tj 0 Tc 0 Tw 5.32 0 0 5.6 90.7086 336.5766 Tm (4)Tj /T1_1 1 Tf -0.012 Tc 0.364 Tw /Span<>> BDC 7.6 0 0 8 36 323.1606 Tm ( )Tj EMC [(Ka)-9.8 (ppa)]TJ 0.048 Tw 14.573 0 Td (59 \(57.3%\))Tj 11.266 0 Td (53 \(51.0%\))Tj 0.364 Tw /Span<>> BDC -25.84 -1.344 Td ( )Tj EMC (Lambda)Tj 0.048 Tw 14.573 0 Td (28 \(27.2%\))Tj 11.266 0 Td (40 \(38.5%\))Tj 0.012 Tw 5.32 0 0 5.6 36 303.2408 Tm (1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 300.5768 Tm [(Missing informa)-9.8 (tion for 1 pa)-9.7 (tient in )37.2 (Thal + Dex arm)]TJ 0.012 Tw 5.32 0 0 5.6 36 294.7408 Tm (2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 292.0768 Tm [(Missing informa)-9.8 (tion for 19 pa)-9.8 (tients in )37.2 (Thal + Dex arm and 20 pa)-9.7 (tients in Dex alone arm)]TJ 0.012 Tw 5.32 0 0 5.6 36 286.2408 Tm (3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 283.5768 Tm [(Missing informa)-9.8 (tion for 17 pa)-9.8 (tients in )37.2 (Thal + Dex arm and 30 pa)-9.7 (tients in Dex alone arm)]TJ 0.012 Tw 5.32 0 0 5.6 36 277.7408 Tm (4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 7.6 0 0 8 41 275.0768 Tm [(Missing informa)-9.8 (tion for 16 pa)-9.8 (tients in )37.2 (Thal + Dex arm and 11 pa)-9.7 (tients in Dex alone arm)]TJ ET /GS1 gs q 1 0 0 1 405 680.9824 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 680.9824 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 680.7324 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 680.7324 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 670.2305 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 680.7324 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 670.2305 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 669.9805 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 669.9805 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 659.4785 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 669.9805 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 659.4785 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 659.2285 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 659.2285 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 659.2285 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 648.4766 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 648.4766 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 637.9747 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 648.4766 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 637.9747 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 637.7247 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 637.7247 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 627.2228 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 637.7247 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 627.2228 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 626.9728 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 626.9728 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 616.4709 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 626.9728 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 616.4709 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 616.2209 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 616.2209 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 605.719 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 616.2209 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 605.719 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 605.469 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 605.469 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 594.967 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 605.469 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 594.967 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 594.717 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 594.717 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 594.717 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 583.9651 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 583.9651 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 573.4633 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 583.9651 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 573.4633 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 573.2133 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 573.2133 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 562.7113 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 573.2133 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 562.7113 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 562.4613 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 562.4613 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 551.9594 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 562.4613 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 551.9594 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 551.7094 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 551.7094 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 551.7094 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 540.9575 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 540.9575 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 530.4556 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 540.9575 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 530.4556 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 530.2056 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 530.2056 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 519.7037 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 530.2056 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 519.7037 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 405 476.696 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 476.696 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 476.446 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 476.446 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 465.9441 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 476.446 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 465.9441 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 465.6941 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 465.6941 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 455.4422 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 495.72 465.6941 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 455.4422 cm 0 0 m 0 10.002 l S Q 1 w q 1 0 0 1 324 723.6481 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 723.6481 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 723.6481 cm 0 0 m 80.28 0 l S Q 0.5 w q 1 0 0 1 405 702.4862 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 495.72 702.4862 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 324 702.2362 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 702.2362 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 702.2362 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 691.4843 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 691.4843 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 691.4843 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 487.1979 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 487.1979 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 487.1979 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324 519.4537 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 519.4537 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 508.9517 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 519.4537 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 508.9517 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 508.7017 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 508.7017 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405 498.1998 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.72 508.7017 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.72 498.1998 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324 497.9498 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 497.9498 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 497.9498 cm 0 0 m 80.28 0 l S Q 1 w q 1 0 0 1 324 454.9422 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 454.9422 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 454.9422 cm 0 0 m 80.28 0 l S Q 0.5 w q 1 0 0 1 324 442.0302 cm 0 0 m 81 0 l S Q q 1 0 0 1 405 442.0302 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.72 442.0302 cm 0 0 m 80.28 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.017 Tc 8 0 0 8 324 727.248 Tm [(T)74.2 (able 8:)]TJ /Span<>> BDC ( )Tj EMC 5 0 Td (Baseline Disease Characteristics \(Study 2\))Tj -0.012 Tc 7.6 0 0 8 324 705.8361 Tm (Disease Characteristic)Tj 0.012 Tw 11.319 1.062 Td [(THALOMID/De)10.2 (xamethasone)]TJ 0 Tc 0 Tw 7.6 0 0 8 490.692 714.3361 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 438.4556 705.8361 Tm (\(N=235\))Tj 8.038 1.062 Td [(Placebo/De)10.2 (xamethasone)]TJ 0 Tc 0 Tw 7.6 0 0 8 572.4227 714.3361 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 524.0806 705.8361 Tm (\(N=235\))Tj 0.048 Tw -26.326 -1.479 Td [(Baseline MM Stage \(Durie-Salmon\),)37.2 ( n \(%\))]TJ /T1_1 1 Tf 0 Tc 0.352 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC (I)Tj -0.012 Tc 0.048 Tw 15.786 0 Td (2 \(1\))Tj 11.266 0 Td (2 \(1\))Tj 0.364 Tw /Span<>> BDC -27.052 -1.344 Td ( )Tj EMC (II)Tj 0.048 Tw 15.318 0 Td (76 \(32\))Tj 11.266 0 Td (88 \(37\))Tj 0.364 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC (III)Tj 0.048 Tw 15.084 0 Td (157 \(69\))Tj 11.266 0 Td (145 \(62\))Tj /T1_0 1 Tf -26.35 -1.344 Td [(ECOG P)24.2 (erformance Status,)37.2 ( n \(%\))]TJ /T1_1 1 Tf 0 Tc 0.352 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC (0)Tj -0.012 Tc 0.048 Tw 15.318 0 Td (40 \(17\))Tj 11.266 0 Td (54 \(23\))Tj 0 Tc 0.352 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC (1)Tj -0.012 Tc 0.048 Tw 15.084 0 Td (124 \(53\))Tj 11.266 0 Td (112 \(48\))Tj 0 Tc 0.352 Tw /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC (2)Tj -0.012 Tc 0.048 Tw 15.318 0 Td (70 \(30\))Tj 11.266 0 Td (68 \(29\))Tj 0 Tc 0.352 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC (3)Tj -0.012 Tc 0.048 Tw 15.786 0 Td (0 \(0\))Tj 10.973 0 Td (1 \(<1\))Tj 0.364 Tw /Span<>> BDC -26.758 -1.344 Td ( )Tj EMC (Missing)Tj 0.048 Tw 15.492 0 Td (1 \(<1\))Tj 11.56 0 Td (0 \(0\))Tj /T1_0 1 Tf -27.052 -1.344 Td [(L)37.2 (ytic Bone Lesions,)37.1 ( n \(%\))]TJ /T1_1 1 Tf 0.364 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC (Present)Tj 0.048 Tw 15.084 0 Td (185 \(79\))Tj 11.266 0 Td (188 \(80\))Tj 0.364 Tw /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC (Absent)Tj 0.048 Tw 15.318 0 Td (49 \(21\))Tj 11.266 0 Td (46 \(20\))Tj 0.364 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC [(Missing)-12 ( )]TJ 0.048 Tw 15.492 0 Td (1 \(<1\))Tj 11.266 0 Td (1 \(<1\))Tj /T1_0 1 Tf -26.758 -1.344 Td [(Bone Marrow Aspirate/Biopsy Cellularity)55.2 (,)37.2 ( n \(%\))]TJ /T1_1 1 Tf 0.364 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC (Normal)Tj 0.048 Tw 15.084 0 Td (102 \(43\))Tj 11.266 0 Td (108 \(46\))Tj 0.364 Tw /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC (Hyperplasia)Tj 0.048 Tw 15.318 0 Td (77 \(33\))Tj 11.266 0 Td (76 \(32\))Tj 0.364 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC (Hypoplasia)Tj 0.048 Tw 15.318 0 Td (53 \(23\))Tj 11.266 0 Td (50 \(21\))Tj 0.364 Tw /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC (Missing)Tj 0.048 Tw 15.786 0 Td (3 \(1\))Tj 10.973 0 Td (1 \(<1\))Tj /T1_0 1 Tf 0.012 Tw -26.758 -1.344 Td (Baseline )Tj /C2_0 1 Tf 0 Tc 0 Tw 3.565 0 Td <0060>Tj /T1_0 1 Tf -0.012 Tc 0.048 Tw 0.536 0 Td [(-2 Microglobulin,)37.2 ( n \(%\))]TJ /T1_1 1 Tf /Span<>> BDC -4.101 -1.344 Td ( )Tj EMC 0.592 0 Td (\0332.5 mg/L)Tj 14.726 0 Td (33 \(14\))Tj 11.266 0 Td (35 \(15\))Tj /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC 0.592 0 Td (>2.5 mg/L)Tj 14.492 0 Td (200 \(85\))Tj 11.266 0 Td (199 \(85\))Tj 0.364 Tw /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC (Missing)Tj 0.048 Tw 15.786 0 Td (2 \(1\))Tj 10.973 0 Td (1 \(<1\))Tj -26.758 -1.479 Td [(KEY)37.2 (:)37.2 ( ECOG=Eastern Coopera)-9.8 (tive Oncolog)-9.8 (y Group)]TJ -0.01 Tc 0.083 Tw 8 0 0 8 324.0002 423.7502 Tm [(In Stud)-9.9 (y 1,)37.1 ( response ra)-9.9 (te was the primar)-17.9 (y endpoint.)37.1 ( Response ra)-9.9 (tes based on serum)-9.9 ( )]TJ -0.008 Tc 0.096 Tw 0 -1.044 Td [(or )0.5 (urine )0.5 (para)-10.2 (protein measurements were signi\036cantly )0.5 (higher in )0.5 (the )0.5 (combina)-10.2 (tion )0.5 (arm)-8 ( )]TJ -0.001 Tc 0.129 Tw 0 -1.044 Td [(\(52% vs.)37 ( 36%\).)37 ( )37.1 (The primar)-18 (y ef\036cac)20 (y endpoint in Stud)-10 (y 2 was time to progression)-1 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.044 Td [(\(TTP\),)37.4 ( de\036ned as the time from randomiza)-9.6 (tion to the \036rst documenta)-9.7 (t)0.5 (ion of disease)-5 ( )]TJ -0.006 Tc 0.104 Tw 0 -1.044 Td [(progression,)36.9 ( based on the myeloma response criteria.)36.9 ( )36.7 (A preplanned interim analysis)-6 ( )]TJ -0.015 Tc 0.061 Tw 0 -1.044 Td [(for Stud)-10.3 (y 2 demonstra)-10.3 (ted tha)-10.2 (t the combina)-10.3 (tion of )37.2 (THALOMID plus dexamethasone was)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(superior to placebo plus dexamethasone with respect to )37.2 (TTP \(T)74.1 (able 9\).)]TJ ET /GS1 gs q 1 0 0 1 405.0002 305.7925 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 305.7925 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 305.5425 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 305.5425 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 295.0406 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 305.5425 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 295.0406 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 294.7906 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 294.7906 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 284.2887 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 294.7906 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 284.0387 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 284.0387 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 273.5368 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 284.0387 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 273.2868 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 273.2868 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 273.2868 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 262.5349 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 262.5349 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 252.033 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 262.5349 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 252.033 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 251.783 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 251.783 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 241.2811 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 251.783 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 241.2811 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 241.0311 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 241.0311 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 230.5291 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 241.0311 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 230.2791 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 230.2791 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 230.2791 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 219.5272 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 219.5272 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 209.0253 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 219.5272 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 209.0253 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 208.7753 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 208.7753 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 198.2734 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 208.7753 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 198.2734 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 198.0234 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 198.0234 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 187.5215 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 495.7202 198.0234 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 187.5215 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0002 187.2715 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 187.2715 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 405.0002 177.0196 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 495.7202 187.2715 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 495.7202 177.0196 cm 0 0 m 0 10.002 l S Q 1 w q 1 0 0 1 324.0002 348.4583 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 348.4583 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 348.4583 cm 0 0 m 80.28 0 l S Q 0.5 w q 1 0 0 1 405.0002 327.2964 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 495.7202 327.2964 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 324.0002 327.0464 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 327.0464 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 327.0464 cm 0 0 m 80.28 0 l S Q q 1 0 0 1 324.0002 316.2945 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 316.2945 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 316.2945 cm 0 0 m 80.28 0 l S Q 1 w q 1 0 0 1 324.0002 176.5196 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 176.5196 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 176.5196 cm 0 0 m 80.28 0 l S Q 0.5 w q 1 0 0 1 324.0002 95.6077 cm 0 0 m 81 0 l S Q q 1 0 0 1 405.0002 95.6077 cm 0 0 m 90.72 0 l S Q q 1 0 0 1 495.7202 95.6077 cm 0 0 m 80.28 0 l S Q BT /GS2 gs /T1_0 1 Tf 8 0 0 8 324.0002 352.0583 Tm [(T)74.2 (able 9:)]TJ /Span<>> BDC ( )Tj EMC 5 0 Td [(Summar)-17.7 (y of Efficac)10.2 (y \(Study 2\))]TJ -0.012 Tc 0.012 Tw 7.6 0 0 8 407.5113 339.1464 Tm [(Thalidomide/De)10.2 (xamethasone)]TJ 0 Tc 0 Tw 7.6 0 0 8 493.2092 339.1464 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 438.4558 330.6464 Tm (\(N=235\))Tj 8.038 1.062 Td [(Placebo/De)10.2 (xamethasone)]TJ 0 Tc 0 Tw 7.6 0 0 8 572.4229 339.1464 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 524.0808 330.6464 Tm (\(N=235\))Tj 0.048 Tw -26.326 -1.479 Td [(T)18.2 (ime to Progression)]TJ /T1_1 1 Tf -0.115 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC 0.592 0 Td (Progressed)Tj /Span<>> BDC ( )Tj EMC (\226)Tj /Span<>> BDC ( )Tj EMC [(n )-162.8 (\(%\))]TJ 0.048 Tw 14.726 0 Td (72 \(31\))Tj 11.033 0 Td (126 \(54\))Tj /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC 0.592 0 Td [(Median \(W)18.2 (eeks\) \(95% CI\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 398.0723 299.9746 Tm (a)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 427.5872 297.3106 Tm [(97.7 \(61.86,)37.1 ( NR\))]TJ 10.742 0 Td [(28.3 \(27.71,)37.1 ( 36.43\))]TJ /Span<>> BDC -24.372 -1.344 Td ( )Tj EMC 0.592 0 Td [(Hazard Ra)-9.7 (tio \(95% CI\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 389.1832 289.2227 Tm (b)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 467.4236 286.5587 Tm [(0.43 \(0.32,)37.2 ( 0.58\))]TJ 0.364 Tw /Span<>> BDC -18.871 -1.344 Td ( )Tj EMC (P-value)Tj 0 Tc 0 Tw 5.32 0 0 5.6 349.0851 278.4708 Tm (c)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 477.5436 275.8068 Tm (< 0.0001)Tj /T1_0 1 Tf -20.203 -1.344 Td [(Overall Sur)-17.7 (viv)16.2 (al)]TJ /T1_1 1 Tf -0.115 Tw /Span<>> BDC 0 -1.344 Td ( )Tj EMC 0.592 0 Td [(Dea)-9.7 (th)]TJ /Span<>> BDC ( )Tj EMC (\226)Tj /Span<>> BDC ( )Tj EMC [(n )-162.8 (\(%\))]TJ 0.048 Tw 14.726 0 Td (57 \(24\))Tj 11.266 0 Td (68 \(29\))Tj /Span<>> BDC -26.584 -1.344 Td ( )Tj EMC 0.592 0 Td [(Median \(W)18.2 (eeks\) \(95% CI\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 398.0723 246.2151 Tm (a)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 428.0158 243.5511 Tm [(NR \(112.14,)37.2 ( NR\))]TJ 10.742 0 Td [(128.6 \(113.43,)37.2 ( NR\))]TJ /Span<>> BDC -24.429 -1.344 Td ( )Tj EMC 0.592 0 Td [(Hazard Ra)-9.7 (tio \(95% CI\))]TJ 0 Tc 0 Tw 5.32 0 0 5.6 389.1832 235.4632 Tm (b)Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 467.4236 232.7991 Tm [(0.82 \(0.57,)37.2 ( 1.16\))]TJ /T1_0 1 Tf -18.871 -1.344 Td (Myeloma Response Rate)Tj 0 Tc 0 Tw 5.32 0 0 5.6 396.7448 224.7112 Tm (d)Tj -0.012 Tc -0.115 Tw /Span<>> BDC 7.6 0 0 8 399.3398 222.0472 Tm ( )Tj EMC (\226)Tj /Span<>> BDC ( )Tj EMC [(n )-162.8 (\(%\))]TJ /T1_1 1 Tf 0.048 Tw /Span<>> BDC -9.913 -1.344 Td ( )Tj EMC 0.592 0 Td (Complete Response \(CR\))Tj 14.96 0 Td (18 \(8\))Tj 11.5 0 Td (6 \(3\))Tj /Span<>> BDC -27.052 -1.344 Td ( )Tj EMC 0.592 0 Td [(P)18.2 (artial Response \(PR\))]TJ 14.492 0 Td (130 \(55\))Tj 11.266 0 Td (102 \(43\))Tj -0.115 Tw /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC 0.592 0 Td [(Overall )-162.8 (Response )-162.7 (\(CR)]TJ /Span<>> BDC ( )Tj EMC (+)Tj /Span<>> BDC ( )Tj EMC [(PR\))-12 ( )]TJ 0.048 Tw 14.492 0 Td (148 \(63\))Tj 11.266 0 Td (108 \(46\))Tj /Span<>> BDC -26.35 -1.344 Td ( )Tj EMC 0.592 0 Td (95% CI \(%\))Tj 14.63 0 Td [(\(56,)37.2 ( 69\))]TJ 11.266 0 Td [(\(39,)37.2 ( 53\))]TJ 0.012 Tw 5.32 0 0 5.6 324.0003 169.8717 Tm (a)Tj /Span<>> BDC ( )Tj EMC -0.005 Tc 0.081 Tw 7.6 0 0 8 329.0003 167.2077 Tm [(T)0.5 (h)0.5 (e)0.5 ( 95)0.5 (%)0.5 ( c)0.5 (o)0.5 (n)0.5 (f)0.5 (i)0.5 (de)0.5 (n)0.5 (c)0.5 (e)0.5 ( i)0.5 (n)0.5 (t)0.5 (e)0.5 (r)-17.5 (v)0.5 (a)0.5 (ls)0.5 ( a)0.5 (b)0.5 (o)0.5 (u)0.5 (t)0.5 ( t)0.5 (h)0.5 (e me)0.5 (d)0.5 (i)0.5 (a)0.5 (n)0.5 ( o)0.5 (v)0.5 (e)0.5 (r)0.5 (a)0.5 (ll)0.5 ( )36.9 (T)0.5 (T)0.5 (P)129.5 (,)37.4 ( o)0.5 (r)0.5 ( m)0.5 (e)0.5 (d)0.5 (i)0.5 (a)0.5 (n)0.5 ( o)0.5 (v)0.5 (er)0.5 (a)0.5 (l)0.5 (l)0.5 ( s)0.5 (u)0.5 (r)-17.5 (v)0.5 (iv)0.5 (a)0.5 (l)0.5 (.)]TJ 0 Tc 0 Tw 7.6 0 0 8 576.0002 167.2077 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 329.0003 158.7077 Tm [(CI:)37.2 ( confidence inter)-17.8 (val; NR:)37.2 ( not reached.)]TJ 0.012 Tw 5.32 0 0 5.6 324.0003 152.8717 Tm (b)Tj /Span<>> BDC ( )Tj EMC -0.008 Tc 0.07 Tw 7.6 0 0 8 329.0003 150.2077 Tm [(Based on a proportional hazards model comparing the hazard functions ass\ ocia)-10.1 (ted with)-8 ( )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td [(trea)-9.8 (tment groups \(thalidomide/dexamethasone:placebo/dexamethasone\).)]TJ 0.012 Tw 5.32 0 0 5.6 324.0003 135.8717 Tm (c)Tj /Span<>> BDC ( )Tj EMC -0.009 Tc 0.063 Tw 7.6 0 0 8 329.0003 133.2077 Tm [(P-value based on )0.5 (the interim analysis )0.5 (was )0.5 (compared )0.5 (with the )0.5 (nominal )0.5 (significance )0.5 (level)-9 ( )]TJ -0.006 Tc 0.079 Tw 0 -1.062 Td [(of 0.0027.)37 ( Based on a one-sided unstra)-9.9 (tified log rank test of sur)-18 (vival cur)-18 (ve differences)-6 ( )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td [(between trea)-9.8 (tment groups.)]TJ 0.012 Tw 5.32 0 0 5.6 324.0003 110.3717 Tm (d)Tj /Span<>> BDC ( )Tj EMC -0.015 Tc 0.036 Tw 7.6 0 0 8 329.0003 107.7077 Tm [(D)0.5 (i)0.5 (s)0.5 (e)0.5 (a)0.5 (s)0.5 (e)0.5 ( )0.5 (r)0.6 (e)0.5 (s)0.5 (p)0.5 (o)0.5 (n)0.5 (s)0.5 (e)0.5 ( )0.5 (a)0.5 (s)0.5 (s)0.5 (e)0.5 (s)0.5 (s)0.5 (m)0.5 (e)0.6 (n)0.5 (t)0.5 (s)0.5 ( )0.5 (w)0.5 (e)0.5 (r)0.5 (e)0.5 ( )0.5 (d)0.5 (e)0.5 (t)0.5 (e)0.5 (r)0.6 (m)0.5 (i)0.5 (n)0.5 (e)0.5 (d)0.5 ( )0.5 (a)0.5 (c)0.5 (c)0.5 (o)0.5 (r)0.5 (d)0.5 (i)0.5 (n)0.5 (g)0.5 ( )0.5 (t)0.5 (o)0.6 ( )0.5 (t)0.5 (h)0.5 (e)0.5 ( )0.5 (B)0.5 (l)0.5 (a)0.5 (d)0.5 (\351)0.5 ( )0.5 (c)0.5 (r)0.5 (i)0.5 (t)0.5 (e)0.5 (r)0.5 (i)0.6 (a)0.5 (.)37.5 ( )0.5 (R)0.5 (e)0.5 (s)0.5 (p)0.5 (o)0.5 (n)0.5 (s)0.5 (e)-15 ( )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td [(is the highest assessment of response during the trea)-9.8 (tment phase of the stud)-9.8 (y)55.2 (.)]TJ -0.001 Tc 0.13 Tw 8 0 0 8 324.0002 77.3276 Tm [(The Ka)-10.1 (plan-Meier plot of the time to progression by trea)-10 (tment group is presented)-1 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(in F)18.2 (igure 1.)]TJ ET endstream endobj 87 0 obj <> endobj 93 0 obj [95 0 R] endobj 94 0 obj <>stream H\Mj0 >3IJ v@iJjhl8ܾ3Lzx> endobj 96 0 obj <> endobj 97 0 obj <> endobj 98 0 obj <>stream Hj` endstream endobj 99 0 obj <>stream HWST~ZP ˇl̊WUnDKWd1DD F,c քa:e2J)12:Dm#8꘴ulqRg{8=3motB]6;eo!Dlm|+1m7m\sY01yƷ|ol/_Q?M~]}u9þ/~t^`+Ɛ'ίDrz]s}(O՞=vL2h~g:`ڥax pXSӻgЇab1)y ^5HLi(eHRD{B#}$G-c ԻE(=̰E>IM-1'4lJTc,T)6<~%:SGQۤJI1Jı26"x)6jz_ *1BjÐҖbRdjK6sJVp.b!0rHznt4qX)wB5i"K+|k<xN&/YŪz},l)yX” _GZEC< LUܞBK8 r%'*;hg4͡pOW;VVuUL,Q]z]rgb}ƙnQq:5ak iWEX{9|S( /Oz>hoT|tiOEU-t?ʦzu+l[r{bl"c O^ZAP~.` qX34p%jɅD31U%9̬ꜞ>TLwxtZI:d_KN h{xJӭj_4nnƿTZcTVP֤ Ɗ.RQBhyoYtDnj6ܫ+={%UI0+jLRjWH:f;Tÿ_OOG o7kVW؛uh}~?OC߇w;m^֫S ʛku͠װ_KE9 SpBMM*Q Zޫ)+I5ڳWԝEO0ZJh> "ɔ cDx.2GLeZNE-b'G4Ôy>5ؼ^{eqž=T/*_Xne̻<'AwRݎ}5cݢ#̛Qn7RB7뉹u^Aגg>yj\Tf aKaxcftO39&8y:Xx<O` <H8"[z<r,;z10қ`5<\:xEpx<X : 83?W?HSX}*5{W|>{{"(U{: nVyt*|vTuSG3wX^\Ʋ ;pgX{nkRE"jNhd~F׾"?S$2?iHvLW' endstream endobj 91 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q 0.5 w /GS1 gs q 1 0 0 1 36 614.5295 cm 0 0 m 30.305 0 l S Q q 1 0 0 1 36 357.5561 cm 0 0 m 32.262 0 l S Q q 1 0 0 1 36 306.0767 cm 0 0 m 33.121 0 l S Q q 1 0 0 1 36 246.1674 cm 0 0 m 31.295 0 l S Q q 1 0 0 1 36 160.9685 cm 0 0 m 48.165 0 l S Q q 1 0 0 1 36 109.4891 cm 0 0 m 92.534 0 l S Q BT /T1_0 1 Tf -0.012 Tc 0.072 Tw 8 0 0 8 36 727.248 Tm [(with er)-17.6 (ythema nodosum leprosum \(ENL\); ho)-9.6 (wever)74.4 (,)37.3 ( it has also been sho)-9.7 (wn to increase)-12 ( )]TJ 0.013 Tc 0.163 Tw 0 -1.054 Td (plasma TNF-)Tj /C2_0 1 Tf 0 Tc 0 Tw <005F>Tj /T1_0 1 Tf 0.013 Tc 0.2 Tw 5.69 0 Td [( )0.5 (levels )0.5 (in )0.5 (HIV)17.9 (-seropositive )0.5 (pa)-10.1 (tients.)36.9 ( Other )0.5 (anti-inflamma)-10 (tor)-18.1 (y and)13 ( )]TJ -0.012 Tc 0.074 Tw -5.69 -1.054 Td [(immunomodula)-10 (tor)-18 (y properties of 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(Healthy Subjects \(n=14\))Tj -8.359 -1.434 Td (50 mg)Tj 7.674 0 Td (4.9 \(16%\))Tj 6.042 0 Td (0.62 \(52%\))Tj 6.001 0 Td (2.9 \(66%\))Tj 5.04 0 Td (5.52 \(37%\))Tj -24.992 -1.434 Td (200 mg)Tj 7.674 0 Td (18.9 \(17%\))Tj 6.276 0 Td (1.76 \(30%\))Tj 6.001 0 Td (3.5 \(57%\))Tj 5.04 0 Td (5.53 \(25%\))Tj -24.992 -1.434 Td (400 mg)Tj 7.674 0 Td (36.4 \(26%\))Tj 6.276 0 Td (2.82 \(28%\))Tj 6.001 0 Td (4.3 \(37%\))Tj 5.04 0 Td (7.29 \(36%\))Tj -18.798 -1.434 Td [(P)18.2 (a)-9.8 (tients with Hansen\222)55.2 (s Disease \(n=6\))]TJ -6.194 -1.434 Td (400 mg)Tj 7.326 0 Td (46.4 \(44.1%\))Tj 6.276 0 Td (3.44 \(52.6%\))Tj 6.349 0 Td (5.7 \(27%\))Tj 5.04 0 Td (6.86 \(17%\))Tj -0.017 Tc 0.056 Tw 8 0 0 8 36 389.2158 Tm [(Coadministra)-9.8 (tion of )36.6 (THALOMID \(thalidomide\) with a high-fa)-9.8 (t meal causes minor \(<10%\))-17 ( )]TJ 0.042 Tw 0 -1.054 Td [(changes in the obser)-17.8 (ved )36.8 (AUC and C)]TJ 0.017 Tw 5.6 0 0 5.6 138.7563 380.5459 Tm (max)Tj 0.042 Tw 8 0 0 8 147.2703 380.7859 Tm [( values; ho)-9.8 (wever)74.2 (,)37.2 ( it causes an increase in )36.8 (T)]TJ 0.017 Tw 5.6 0 0 5.6 271.8784 380.5459 Tm (max)Tj 0.042 Tw 8 0 0 8 280.3924 380.7859 Tm [( to)-16.9 ( )]TJ 0.048 Tw -30.549 -1.054 Td [(a)-9.8 (pproxima)-9.8 (tely 6 hours.)]TJ 0.017 Tw 0 -1.725 Td (Distribution)Tj -0.004 Tc 0.114 Tw 0 -1.549 Td [(In human plasma,)36.9 ( the geometric mean plasma protein binding was 55% and 66%,)33.1 ( )]TJ 0.011 Tc 0.191 Tw 0 -1.054 Td [(respectively)54.6 (,)36.7 ( for \()]TJ 0 Tc 0 Tw 6.869 0.125 Td (+)Tj 0.011 Tc 0.191 Tw 0.611 -0.125 Td [(\)-\(R\)- and \(-\)-\(S\)-thalidomide.)36.6 ( In a pharmacokinetic stud)-10.4 (y of)11 ( )]TJ -0.012 Tc 0.074 Tw -7.48 -1.054 Td [(thalidomide in HIV)18 (-seropositive adult male subjects receiving thalidomide 100 mg/day)55.1 (,)25 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.054 Td (thalidomide was detectable in the semen.)Tj 0.017 Tw 0 -1.725 Td (Metabolism)Tj 0.007 Tc 0.168 Tw 0 -1.549 Td (In a )Tj -0.007 Tw 5.6 0 0 5.6 51.6918 297.3508 Tm (14)Tj 0.168 Tw 8 0 0 8 57.1443 294.6868 Tm [(C-radiolabel )37 (ADME stud)-9.8 (y in humans,)37.2 ( unchanged drug is the predominant)7 ( )]TJ -0.014 Tc 0.063 Tw -2.643 -1.054 Td [(circula)-9.9 (ting component.)37.1 ( )36.6 (Thalidomide is not a substra)-9.9 (te of the c)20.1 (ytochrome P450 system.)]TJ 0 Tc 0.136 Tw 0 -1.054 Td [(At thera)-10.3 (peutic concentra)-10.2 (tions,)36.7 ( thalidomide is not an inhibitor or inducer of human )]TJ 0.007 Tc 0.166 Tw 0 -1.054 Td [(c)20.5 (y)0.6 (t)0.5 (o)0.6 (c)0.5 (h)0.5 (r)0.6 (o)0.5 (m)0.6 (e)0.5 ( P)0.6 (4)0.5 (5)0.5 (0)0.6 ( e)0.5 (n)0.5 (z)0.6 (y)0.5 (m)0.6 (e)0.5 (s)0.6 ( )]TJ /T1_1 1 Tf [(i)0.6 (n)0.5 ( v)0.5 (i)0.6 (t)0.5 (r)0.6 (o)]TJ /T1_0 1 Tf 13.614 0 Td [(.)37.5 ( P)0.6 (h)0.5 (a)0.6 (r)0.5 (m)0.5 (a)0.6 (c)0.5 (o)0.6 (k)0.5 (i)0.6 (n)0.5 (e)0.5 (t)0.6 (i)0.5 (c)0.5 ( d)0.6 (r)0.5 (u)0.6 (g)0.5 (-)0.5 (d)0.6 (r)0.5 (u)0.6 (g)0.5 ( i)0.5 (n)0.5 (t)0.6 (e)0.5 (r)0.6 (a)0.5 (c)0.6 (t)0.5 (i)0.6 (o)0.5 (n)0.5 (s)0.6 ( w)0.5 (i)0.5 (t)0.6 (h)7 ( )]TJ -0.017 Tc 0.048 Tw -13.614 -1.054 Td [(substra)-9.7 (tes,)37.2 ( inhibitors or inducers of CYP450 are not anticipa)-9.8 (ted.)]TJ 0.017 Tw 0 -1.725 Td [(Elimina)-9.8 (tion)]TJ -0.003 Tc 0.119 Tw 0 -1.549 Td [(The mean elimina)-10 (tion half-life of thalidomide in plasma follo)-10.1 (wing single oral doses)-3 ( )]TJ -0.017 Tc 0.042 Tw 0 -1.054 Td [(between 50 mg and 400 mg was 5.5 to 7.3 hours.)37.2 ( F)20.2 (ollo)-9.7 (wing a single 400 mg oral dose)-17 ( )]TJ -0.007 Tc 0.097 Tw 0 -1.054 Td [(of radiolabeled thalidomide,)37.3 ( the total mean recover)-17.7 (y was 93.6% of the administered)-7 ( )]TJ -0.003 Tc 0.122 Tw 0 -1.054 Td [(dose by Day 8.)36.5 ( )37.3 (The majority of the radioactive dose was excreted within 48 hours)-3 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.054 Td [(follo)-10.4 (wing dose administra)-10.4 (tion.)36.6 ( In humans,)36.6 ( )]TJ 0.016 Tw 5.6 0 0 5.6 158.1339 203.722 Tm (14)Tj 0.06 Tw 8 0 0 8 163.3352 201.058 Tm [(C-thalidomide is primarily excreted in urine)-16 ( )]TJ -0.017 Tc 0.055 Tw -15.917 -1.054 Td [(\(91.9% )0.6 (of )0.5 (the )0.5 (radioactive )0.6 (dose\) )0.5 (mainly )0.5 (as )0.5 (hydrolytic )0.5 (metabolites )0.5 (while )0.5 (fecal )0.5 (excretion )0.5 (is)-17 ( )]TJ -0.011 Tc 0.077 Tw 0 -1.054 Td [(minor \(<2% of the dose\).)37.3 ( Unchanged thalidomide is not elimina)-9.7 (ted by the kidney to a)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.054 Td (notable degree \(<3.5% of the dose\).)Tj 0.011 Tw 0 -1.725 Td [(Effects )-36.8 (of W)18.2 (eight)]TJ -0.019 Tc 0.036 Tw 0 -1.549 Td [(There is a linear rela)-10.3 (tionship between bod)-10.3 (y weight and estima)-10.3 (ted thalidomide c)19.7 (learance.)18 ( )]TJ -0.012 Tc 0.077 Tw 0 -1.054 Td [(In MM pa)-10.4 (tients with bod)-10.4 (y weight from 47-133 kg,)36.5 ( thalidomide c)19.5 (learance ranged from)-12 ( )]TJ -0.017 Tc 0.058 Tw 0 -1.054 Td [(a)-9.8 (pproxima)-9.8 (tely 6-12 L/h,)37.2 ( representing an increase in thalidomide c)20.2 (learance of 0.605 L/h)-17 ( )]TJ 0.048 Tw 0 -1.054 Td [(per 10 kg bod)-9.8 (y weight increase.)]TJ 0 -1.725 Td [(Effects of )37.2 (Age,)37.2 ( Gender and Race)]TJ -0.008 Tc 0.092 Tw 0 -1.549 Td [(Analysis of the da)-9.7 (ta from pharmacokinetic studies in healthy volunteers and pa)-9.6 (tients)-8 ( )]TJ 0.095 Tw 0 -1.054 Td [(with Hansen\222)54.8 (s disease ranging in a)-10.2 (ge from 20 to 69 years does not reveal an)-10.1 (y a)-10.2 (ge-)]TJ -0.017 Tc 0.048 Tw 0 -1.054 Td [(rela)-9.7 (ted changes.)]TJ -0.003 Tc 0.116 Tw 0 -1.774 Td [(W)0.5 (h)0.6 (i)0.5 (l)0.5 (e)0.6 ( a)0.6 ( c)0.5 (o)0.6 (m)0.5 (p)0.5 (a)0.6 (r)0.5 (a)-9.5 (t)0.6 (i)0.5 (v)0.5 (e)0.6 ( t)0.5 (r)0.5 (i)0.6 (a)0.5 (l)0.5 ( o)0.6 (f)0.5 ( t)0.5 (h)0.5 (e)0.6 ( e)0.5 (f)0.6 (f)0.5 (e)0.5 (c)0.6 (t)0.5 (s)0.5 ( o)0.6 (f)0.5 ( g)0.5 (e)0.5 (n)0.6 (d)0.5 (e)0.5 (r)0.6 ( o)0.5 (n)0.5 ( t)0.6 (h)0.5 (a)0.5 (l)0.6 (i)0.5 (d)0.5 (o)0.6 (m)0.5 (i)0.5 (d)0.6 (e)0.5 ( p)0.5 (h)0.5 (a)0.6 (r)0.5 (m)0.6 (a)0.5 (c)0.5 (o)0.6 (k)0.5 (i)0.5 (n)0.6 (e)0.5 (t)0.5 (i)0.6 (c)0.5 (s)-3 ( )]TJ -0.01 Tc 0.083 Tw 0 -1.054 Td [(has not been conducted,)37.3 ( examina)-9.8 (tion of the da)-9.7 (ta for thalidomide does not reveal an)-9.8 (y)-9.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.054 Td (signi\036cant gender differences in pharmacokinetic parameter values.)Tj 0 -1.774 Td [(Pharmacokinetic differences due to race ha)-9.8 (ve not been studied.)]TJ ET q 1 0 0 1 324 726.248 cm 0 0 m 127.41 0 l S Q BT 8 0 0 8 324 727.248 Tm [(Pharmacokinetic Da)-9.8 (ta in Special P)18.2 (opula)-9.8 (tions)]TJ /T1_1 1 Tf 0 Tc 0.134 Tw 0 -1.539 Td [(HIV)18 (-seropositive Subjects:)]TJ /T1_0 1 Tf /Span<>> BDC ( )Tj EMC 9.781 0 Td [( )36.9 (There is no a)-10 (pparent signi\036cant difference in measured )]TJ -0.022 Tc 0.036 Tw -9.781 -1.044 Td [(pharmacokinetic parameter )0.5 (values between healthy human )0.5 (subjects )0.5 (and HIV)18.1 (-seropositive)-22 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(subjects follo)-9.8 (wing single-dose administra)-9.8 (tion of )37.2 (THALOMID Ca)-9.8 (psules.)]TJ /T1_1 1 Tf -0.018 Tc 0.036 Tw 0 -1.764 Td [(P)18.1 (a)-9.8 (tients with Hansen\222)55.1 (s Disease:)]TJ /T1_0 1 Tf /Span<>> BDC ( )Tj EMC 11.312 0 Td [( )37.1 (Analysis of da)-9.9 (ta from a small stud)-9.9 (y in Hansen\222)55.1 (s pa)-9.9 (tients)-18 ( )]TJ 0.002 Tc 0.143 Tw -11.312 -1.044 Td [(suggests tha)-9.9 (t these pa)-9.9 (tients,)37.1 ( rela)-9.9 (tive to healthy subjects,)37.1 ( may ha)-9.9 (ve an increased)2 ( )]TJ -0.012 Tc 0.076 Tw 0 -1.044 Td [(bioa)-10.2 (vailability of )37.4 (THALOMID.)36.7 ( )37.4 (The increase is re\035ected both in an increased area under)-12 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.044 Td [(the cur)-17.8 (ve and in increased peak plasma levels.)37.2 ( )37.2 (The c)20.2 (linical signi\036cance of this increase)-17 ( )]TJ 0.048 Tw 0 -1.044 Td [(is unkno)-9.8 (wn.)]TJ /T1_1 1 Tf 0.017 Tw 0 -1.764 Td [(P)18.2 (edia)-9.7 (tric:)]TJ /T1_0 1 Tf 0.048 Tw /Span<>> BDC ( )Tj EMC 3.305 0 Td [( No pharmacokinetic da)-9.7 (ta are a)-9.8 (vailable in subjects belo)-9.8 (w the a)-9.8 (ge of 18 years.)]TJ /T1_1 1 Tf -0.007 Tc 0.102 Tw -3.305 -1.764 Td [(P)17.6 (a)-10.4 (tients )0.6 (with )0.5 (Renal )0.6 (Impairment:)]TJ /T1_0 1 Tf /Span<>> BDC ( )Tj EMC 11.916 0 Td [( )0.5 (Renal )0.5 (impairment )0.5 (is )0.5 (not )0.6 (expected )0.6 (to )0.6 (in\035uence )0.6 (drug)-7 ( )]TJ -0.017 Tc 0.048 Tw -11.916 -1.044 Td (exposure since <3.5% of the dose is excreted in the urine as unchanged d\ rug.)Tj /T1_1 1 Tf -0.012 Tc 0.074 Tw 0 -1.764 Td [(P)18 (a)-9.9 (tients with Hepa)-9.9 (tic Impairment:)]TJ /T1_0 1 Tf /Span<>> BDC ( )Tj EMC 12.349 0 Td [( No c)20 (linical studies ha)-9.9 (ve been conducted in pa)-10 (tients)-12 ( )]TJ -0.017 Tc 0.048 Tw -12.349 -1.044 Td [(with hepa)-9.8 (tic impairment.)]TJ /T1_2 1 Tf 0.017 Tw 0 -2.048 Td (13)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(NONCLINIC)18.2 (AL TOXICOLOGY)]TJ 0.017 Tw -3.375 -1.827 Td (13.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Carcinogenesis,)37.2 ( Mutagenesis,)37.2 ( Impairment of F)20.2 (ertility)]TJ /T1_0 1 Tf -0.008 Tc 0.094 Tw -3.375 -1.584 Td [(T)74.1 (wo-year )0.5 (carcinogenicity )0.5 (studies )0.5 (were )0.5 (conducted )0.5 (in )0.5 (male )0.5 (and )0.5 (female )0.5 (ra)-9.9 (ts )0.5 (and )0.5 (mice.)29 ( )]TJ -0.005 Tc 0.111 Tw 0 -1.044 Td [(No compound-rela)-10.3 (ted tumorigenic effects were obser)-18.3 (ved a)-10.4 (t the highest dose levels)-5 ( )]TJ 0.007 Tc 0.168 Tw 0 -1.044 Td [(of )0.5 (3,000 )0.5 (mg/kg/day )0.5 (to )0.5 (male )0.5 (and )0.5 (female )0.5 (mice )0.6 (\(38-fold )0.5 (grea)-9.8 (ter )0.5 (than )0.5 (the )0.5 (highest)7 ( )]TJ -0.003 Tc 0.121 Tw 0 -1.044 Td [(recommended )0.5 (daily )0.5 (human )0.5 (dose )0.5 (of )0.5 (400 )0.5 (mg based )0.5 (upon )0.5 (bod)-10.2 (y )0.5 (surface )0.5 (area )0.5 ([BSA]\),)34 ( )]TJ -0.013 Tc 0.067 Tw 0 -1.044 Td [(3,000 mg/kg/day to female ra)-9.6 (ts \(75-fold the maximum human dose based upon BSA\),)24 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(and 300 mg/kg/day to male ra)-9.8 (ts \(7.5-fold the maximum human dose based upon BSA\).)]TJ -0.007 Tc 0.099 Tw 0 -1.764 Td [(Thalidomide was neither muta)-9.9 (genic nor genotoxic in the follo)-9.9 (wing assays:)37 ( the )37.4 (Ames)-7 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.044 Td (bacterial \()Tj /T1_1 1 Tf 3.519 0 Td [(S.)37.1 ( typhimurium)]TJ /T1_0 1 Tf ( and )Tj /T1_1 1 Tf [(E.)37.1 ( col)]TJ 0 Tc 0 Tw (i)Tj /T1_0 1 Tf -0.015 Tc 0.06 Tw 9.669 0 Td [(\) reverse muta)-9.9 (tion assay)55.1 (,)37.2 ( a Chinese hamster ovar)-17.8 (y)-15 ( )]TJ -0.017 Tc 0.048 Tw -13.187 -1.044 Td [(cell \(AS52/XPR)18.2 (T\) forward muta)-9.7 (tion assay)55.2 (,)37.2 ( and an )]TJ /T1_1 1 Tf (in vivo)Tj /T1_0 1 Tf [( mouse micronuc)20.2 (leus test.)]TJ -0.001 Tc 0.129 Tw 0 -1.764 Td [(F)23.9 (ertility studies were conducted in male and female rabbits; no compound-\ rela)-10.1 (ted)-1 ( )]TJ -0.013 Tc 0.067 Tw 0 -1.044 Td [(effects in ma)-9.7 (ting and fertility indices were obser)-17.6 (ved a)-9.7 (t an)-9.7 (y oral thalidomide dose level)-13 ( )]TJ -0.012 Tc 0.076 Tw 0 -1.044 Td [(inc)19.7 (luding the highest of 100 mg/kg/day to female rabbits and 500 mg/kg/day \ to male)-12 ( )]TJ -0.01 Tc 0.086 Tw 0 -1.044 Td [(rabbits \(a)-10.3 (pproxima)-10.3 (tely 5- and 25-fold the maximum human dose,)36.6 ( respectively)54.6 (,)36.7 ( based)-10 ( )]TJ -0.004 Tc 0.114 Tw 0 -1.044 Td [(upon BSA\).)37.1 ( )37.2 (T)74 (esticular pa)-9.9 (thological and histopa)-10 (thological effects \(c)20.1 (lassi\036ed as slight\))-4 ( )]TJ -0.008 Tc 0.094 Tw 0 -1.044 Td [(were )0.5 (seen )0.6 (in )0.5 (male )0.5 (rabbits )0.6 (a)-9.9 (t )0.5 (dose )0.5 (levels )0.6 (\03730 )0.5 (mg/kg/day )0.5 (\(a)-9.9 (pproxima)-9.9 (tely )0.5 (1.5-fold )0.6 (the)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td (maximum human dose based upon BSA\).)Tj /T1_2 1 Tf 0.017 Tw 0 -2.048 Td (14)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(CLINIC)18.3 (AL STUDIES)]TJ 0.017 Tw -3.375 -1.827 Td (14.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Multiple Myeloma \(MM\))Tj /T1_0 1 Tf 0.053 Tw -3.375 -1.584 Td [(The ef\036cac)20.2 (y and safety of )37.1 (THALOMID in pa)-9.8 (tients with multiple myeloma were evalua)-9.8 (ted)-17 ( )]TJ 0.005 Tc 0.159 Tw 0 -1.044 Td [(in two randomized,)37 ( multi-center studies \(Stud)-10 (y 1 and Stud)-9.9 (y 2\).)37 ( Stud)-10 (y 1 was an)5 ( )]TJ -0.008 Tc 0.091 Tw 0 -1.044 Td [(o)0.5 (pen)0.5 (-l)0.5 (ab)0.5 (el)0.5 ( st)0.5 (ud)-9.5 (y w)0.5 (hic)0.5 (h ra)0.5 (nd)0.5 (om)0.5 (ize)0.5 (d 207)0.5 ( s)0.5 (ym)0.5 (pto)0.5 (ma)-9.5 (t)0.5 (ic p)0.5 (a)-9.5 (ti)0.5 (en)0.5 (ts wit)0.5 (h ne)0.5 (wly)0.5 ( di)0.5 (a)-9.6 (g)0.5 (no)0.5 (se)0.5 (d)-8 ( )]TJ -0.02 Tc 0.036 Tw 0 -1.044 Td [(MM to )37.3 (THALOMID plus dexamethasone \(N = 103\) versus dexamethasone alone \(N=1\ 04\).)17 ( )]TJ -0.017 Tc 0.056 Tw 0 -1.044 Td [(The )37.4 (THALOMID dose was 200 mg daily and the dexamethasone dose was 40 mg oral\ ly)-17 ( )]TJ -0.009 Tc 0.091 Tw 0 -1.044 Td [(once daily on days 1-4,)36.6 ( 9-12,)36.7 ( and 17-20 ever)-18.3 (y 28-days.)36.7 ( Each group was trea)-10.3 (ted for)-9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(four 28-day c)20.2 (yc)20.2 (les.)]TJ 0.008 Tc 0.172 Tw 0 -1.764 Td [(Stud)-9.6 (y 2 randomized 470 newly dia)-9.6 (gnosed pa)-9.6 (tients with MM to )37.2 (THALOMID plus)8 ( )]TJ 0.016 Tc 0.215 Tw 0 -1.044 Td [(dexamethasone \(N=235\) versus placebo plus dexamethasone \(N=235\).)36.8 ( In the)16 ( )]TJ -0.009 Tc 0.087 Tw 0 -1.044 Td [(THA)0.5 (LOMI)0.5 (D/dex)0.5 (ame)0.5 (thas)0.5 (one)0.5 ( )0.5 (arm)0.5 (,)37.4 ( )0.5 (a)0.5 ( )0.5 (sta)0.5 (rtin)0.5 (g )0.5 (do)0.5 (se )0.6 (of )0.5 (t)0.5 (hal)0.5 (idom)0.5 (ide )0.6 (50 )0.5 (m)0.5 (g )0.5 (wa)0.5 (s )0.5 (e)0.5 (scal)0.5 (a)-9.6 (te)0.5 (d)-9 ( )]TJ -0.002 Tc 0.126 Tw 0 -1.044 Td [(to 200 mg/day \(c)19.7 (yc)19.7 (le 2\) once daily for 28 days.)36.7 ( P)17.6 (a)-10.3 (tients in both trea)-10.3 (tment groups)-2 ( )]TJ -0.01 Tc 0.082 Tw 0 -1.044 Td [(took 40 mg of dexamethasone once daily given on days 1-4,)37.3 ( 9-12,)37.3 ( and 17-20 \(ever)-17.7 (y)-9.9 ( )]TJ -0.011 Tc 0.081 Tw 0 -1.044 Td [(28 )0.5 (days\).)36.7 ( )0.5 (Beginning )0.5 (with )0.5 (Cyc)19.8 (le )0.5 (5,)36.7 ( )0.5 (the )0.5 (dose )0.5 (of )0.5 (dexamethasone )0.5 (was )0.5 (reduced )0.5 (to )0.5 (40 )0.5 (mg)-11 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.044 Td [(once daily on Days 1 to 4 of each c)19.8 (yc)19.9 (le.)36.8 ( )36.8 (T)73.8 (rea)-10.1 (tment continued as tolera)-10.2 (ted until disease)-15 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (progression.)Tj 0.013 Tc 0.197 Tw 0 -1.764 Td [(Baseline demogra)-9.6 (phics for both studies are presented in )37.2 (T)74.4 (able 6 and disease)13 ( )]TJ -0.006 Tc 0.103 Tw 0 -1.044 Td [(characteristics for the stud)-9.8 (y popula)-9.7 (tion are summarized in )37.2 (T)74.2 (ables 7 \(Stud)-9.8 (y 1\) and 8)-6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(\(Stud)-9.8 (y 2\).)]TJ ET endstream endobj 86 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q 0.5 w /GS1 gs q 1 0 0 1 36 616.2367 cm 0 0 m 13.291 0 l S Q q 1 0 0 1 36 431.7269 cm 0 0 m 41.95 0 l S Q q 1 0 0 1 36 363.2064 cm 0 0 m 13.291 0 l S Q q 1 0 0 1 36 252.1028 cm 0 0 m 51.766 0 l S Q q 1 0 0 1 36 101.7204 cm 0 0 m 39.372 0 l S Q BT /T1_0 1 Tf -0.021 Tc 0.036 Tw 8 0 0 8 36 727.1403 Tm [(If pregnanc)20.4 (y does occur during trea)-9.6 (tment,)37.4 ( immedia)-9.7 (tely discontinue the drug.)37.4 ( Under these)-21 ( )]TJ -0.014 Tc 0.062 Tw 0 -1.057 Td [(conditions,)37.3 ( refer the pa)-9.7 (tient to an obstetrician/g)-9.7 (ynecologist experienced in reproductive)-14 ( )]TJ -0.009 Tc 0.09 Tw 0 -1.057 Td [(toxicity for further evalua)-10.1 (tion and counseling.)36.8 ( Report an)-10.1 (y suspected fetal exposure to)-9 ( )]TJ -0.002 Tc 0.124 Tw 0 -1.057 Td [(THALOMID to the FDA via the MedW)18 (a)-9.9 (tch program a)-10 (t 1-800-FDA-1088 and also to)-2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.057 Td [(Celgene Corpora)-9.8 (tion a)-9.8 (t 1-888-423-5436.)]TJ 0 -1.777 Td [(Thalidomide crossed the placenta after administra)-9.8 (tion to pregnant hamsters )]TJ /T1_1 1 Tf 0 Tc 0 Tw (\()Tj -0.017 Tc 0.048 Tw 27.671 0 Td [(see Da)-9.8 (ta\))]TJ /T1_0 1 Tf 0 Tc 0 Tw (.)Tj -0.015 Tc 0.06 Tw -27.671 -1.777 Td [(T)0.5 (h)0.6 (e)0.5 ( )0.6 (e)0.5 (s)0.5 (t)0.6 (i)0.5 (m)0.6 (a)-9.5 (t)0.6 (e)0.5 (d)0.5 ( )0.6 (b)0.5 (a)0.6 (c)0.5 (k)0.6 (g)0.5 (r)0.5 (o)0.6 (u)0.5 (n)0.6 (d)0.5 ( )0.5 (r)0.6 (i)0.5 (s)0.5 (k)0.6 ( )0.5 (o)0.6 (f)0.5 ( )0.6 (m)0.5 (a)0.6 (j)0.5 (o)0.5 (r)0.6 ( )0.5 (b)0.6 (i)0.5 (r)0.5 (t)0.6 (h)0.5 ( )0.6 (d)0.5 (e)0.5 (f)0.6 (e)0.5 (c)0.6 (t)0.5 (s)0.5 ( )0.6 (a)0.5 (n)0.6 (d)0.5 ( )0.6 (m)0.5 (i)0.5 (s)0.6 (c)0.5 (a)0.6 (r)0.5 (r)0.5 (i)0.6 (a)-9.5 (g)0.6 (e)0.5 ( )0.6 (f)0.5 (o)0.5 (r)0.6 ( )0.5 (t)0.6 (h)0.5 (e)0.6 ( )0.5 (i)0.5 (n)0.6 (d)0.5 (i)0.5 (c)0.6 (a)-9.5 (t)0.6 (e)0.5 (d)-15 ( )]TJ -0.013 Tc 0.066 Tw 0 -1.057 Td [(p)0.5 (o)0.6 (p)0.5 (u)0.6 (l)0.5 (a)-9.4 (t)0.5 (i)0.6 (o)0.5 (n)0.6 ( i)0.5 (s)0.6 ( u)0.6 (n)0.5 (k)0.5 (n)0.6 (o)-9.5 (w)0.6 (n)0.5 (.)37.6 ( )37.2 (A)0.5 (l)0.6 (l)0.5 ( p)0.5 (r)0.5 (e)0.6 (g)0.5 (n)0.6 (a)0.5 (n)0.6 (c)0.5 (i)0.6 (e)0.5 (s)0.6 ( h)0.5 (a)-9.4 (v)0.5 (e)0.6 ( a)0.6 ( b)0.6 (a)0.5 (c)0.5 (k)0.6 (g)0.5 (r)0.6 (o)0.5 (u)0.6 (n)0.5 (d)0.6 ( r)0.6 (i)0.5 (s)0.5 (k)0.6 ( o)0.6 (f)0.5 ( b)0.6 (i)0.5 (r)0.6 (t)0.5 (h)0.6 ( d)0.6 (e)0.5 (f)0.6 (e)0.5 (c)0.6 (t)0.5 (,)37.5 ( l)0.5 (o)0.6 (s)0.5 (s)0.5 (,)37.6 ( o)0.6 (r)-13 ( )]TJ 0 -1.057 Td [(o)0.5 (t)0.5 (he)0.5 (r)0.5 ( a)0.5 (dv)0.5 (e)0.5 (r)0.5 (se)0.5 ( o)0.5 (ut)0.5 (c)0.5 (o)0.5 (m)0.5 (es)0.5 (.)37.5 ( )36.8 (Th)0.5 (e)0.5 ( e)0.5 (st)0.5 (i)0.5 (m)0.5 (a)-9.6 (t)0.5 (e)0.5 (d)0.5 ( ba)0.5 (c)0.5 (k)0.5 (gr)0.5 (o)0.5 (un)0.5 (d)0.5 ( r)0.5 (is)0.5 (k)0.5 ( in)0.5 ( t)0.5 (h)0.5 (e U)0.5 (.)0.5 (S)0.5 (.)37.4 ( g)0.5 (e)0.5 (ne)0.5 (r)0.5 (a)0.5 (l p)0.5 (o)0.5 (pu)0.5 (l)0.5 (a)-9.5 (t)0.5 (io)0.5 (n)-13 ( )]TJ -0.017 Tc 0.036 Tw 0 -1.057 Td [(of major birth defects is 2%-4% and of miscarria)-9.7 (ge is 15%-20% of c)20.3 (linically recognized)-17 ( )]TJ 0.017 Tw 0 -1.057 Td (pregnancies.)Tj 0 -1.728 Td [(Da)-9.8 (ta)]TJ /T1_1 1 Tf 0.048 Tw 0 -1.503 Td [(Animal Da)-9.8 (ta)]TJ /T1_0 1 Tf -0.004 Tc 0.116 Tw 0 -1.552 Td [(A pre- and postna)-10.4 (tal reproductive toxicity stud)-10.4 (y was conducted in pregnant female)-3.9 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.057 Td [(rabbits.)36.7 ( Compound-rela)-10.2 (ted increased abortion incidences and eleva)-10.2 (ted fetotoxicity were)-17 ( )]TJ -0.005 Tc 0.11 Tw 0 -1.057 Td [(obser)-18.1 (ved a)-10.1 (t the lo)-10.1 (west oral dose level of 30 mg/kg/day \(a)-10.1 (pproxima)-10.1 (tely 1.5-fold the)-5 ( )]TJ -0.014 Tc 0.065 Tw 0 -1.057 Td [(maximum human dose based upon BSA\) and all higher dose levels.)36.8 ( Neona)-10.2 (tal mortality)-14 ( )]TJ 0.003 Tc 0.15 Tw 0 -1.057 Td [(was eleva)-10.1 (ted a)-10.2 (t oral dose levels to the lacta)-10.1 (ting female rabbits \037150 mg/kg/day)3 ( )]TJ 0.002 Tc 0.141 Tw 0 -1.057 Td [(\()0.5 (a)-9.5 (pp)0.5 (r)0.5 (ox)0.5 (i)0.5 (m)0.5 (a)-9.5 (te)0.5 (l)0.5 (y)0.5 ( 7)0.5 (.5)0.5 (-)0.5 (f)0.5 (o)0.5 (ld)0.5 ( t)0.5 (h)0.5 (e)0.5 ( m)0.5 (ax)0.5 (i)0.5 (m)0.5 (um)0.5 ( hu)0.5 (m)0.5 (an)0.5 ( d)0.5 (o)0.5 (s)0.5 (e ba)0.5 (s)0.5 (e)0.5 (d up)0.5 (o)0.5 (n)0.5 ( B)0.5 (SA)0.5 (\))0.5 (.)37.4 ( N)0.5 (o)0.5 ( d)0.5 (e)0.5 (la)0.5 (y)0.5 ( i)0.5 (n)2 ( )]TJ -0.005 Tc 0.106 Tw 0 -1.057 Td [(po)0.5 (stn)0.5 (a)-9.6 (t)0.5 (al d)0.5 (ev)0.5 (elo)0.5 (pme)0.5 (nt)0.5 (,)37.4 ( in)0.5 (c)20.4 (lud)0.5 (ing)0.5 ( le)0.5 (arn)0.5 (ing)0.5 ( an)0.5 (d me)0.5 (mo)0.5 (r)-17.6 (y fun)0.5 (cti)0.5 (ons)0.5 (,)37.4 ( we)0.5 (re)0.5 ( not)0.5 (ed)0.5 ( a)-9.5 (t the)-5 ( )]TJ -0.011 Tc 0.08 Tw 0 -1.057 Td [(oral dose level to the lacta)-10.2 (ting female rabbits of 150 mg/kg/day \(a)-10.2 (vera)-10.2 (ge thalidomide)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.057 Td [(concentra)-9.8 (tions in milk ranged from 22 to 36 mcg per mL\).)]TJ 0.001 Tc 0.138 Tw 0 -1.777 Td [(In a stud)-9.9 (y conducted in pregnant rabbits,)37.1 ( thalidomide levels in fetal plasma were)1 ( )]TJ 0.016 Tc 0.216 Tw 0 -1.057 Td [(a)-10.4 (pproxima)-10.4 (tely 11% to 73% of the ma)-10.3 (ternal C)]TJ -0.016 Tw 5.6 0 0 5.6 187.3036 502.2374 Tm (max)Tj 0.216 Tw 8 0 0 8 196.3818 502.4774 Tm [(.)36.6 ( In a stud)-10.4 (y conducted with)16 ( )]TJ -0.046 Tc 0.046 Tw 5.6 0 0 5.6 36 496.1855 Tm (14)Tj -0.006 Tc 0.104 Tw 8 0 0 8 41.0854 494.0215 Tm [(C-thalidomide \(150 mg/kg orally\) in pregnant hamsters,)36.9 ( radioactivity was detected)-6 ( )]TJ 0.002 Tc 0.146 Tw -0.636 -1.057 Td [(in the embr)-18.3 (yo,)36.7 ( and the rela)-10.3 (tive concentra)-10.3 (tions of radioactivity in the embr)-18.3 (yo and)2 ( )]TJ -0.009 Tc 0.086 Tw 0 -1.057 Td [(m)0.5 (a)-9.5 (t)0.5 (e)0.5 (rn)0.5 (a)0.5 (l)0.5 ( p)0.5 (l)0.5 (a)0.5 (s)0.5 (ma)0.5 ( w)0.5 (e)0.5 (re)0.5 ( a)0.5 (b)0.5 (o)0.5 (ut)0.5 ( t)0.5 (he)0.5 ( s)0.5 (am)0.5 (e)0.5 ( a)-9.5 (t)0.5 ( 4)0.5 (,)37.5 ( 1)0.5 (2)0.5 ( an)0.5 (d)0.5 ( 2)0.5 (4)0.5 ( ho)0.5 (u)0.5 (r)0.5 (s)0.5 ( a)0.5 (f)0.5 (t)0.5 (e)0.5 (r)0.5 ( d)0.5 (o)0.5 (s)0.5 (in)0.5 (g)0.5 (.)37.4 ( B)0.5 (a)0.5 (s)0.5 (e)0.5 (d o)0.5 (n)-9 ( )]TJ -0.011 Tc 0.077 Tw 0 -1.057 Td [(the radioactivity da)-9.7 (ta,)37.3 ( thalidomide crossed the placental barrier)74.3 (,)37.3 ( and the fetal levels of)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.057 Td [(drug-rela)-9.8 (ted ma)-9.8 (terial were a)-9.7 (pproxima)-9.8 (tely similar to those of ma)-9.8 (ternal levels.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.886 Td (8.2)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(Lactation)-17 ( )]TJ /T1_0 1 Tf 0.048 Tw -3.375 -1.548 Td [(Risk Summar)-17.8 (y)]TJ -0.019 Tc 0.036 Tw 0 -1.552 Td [(T)0.5 (h)0.5 (e)0.5 (r)0.5 (e)0.5 ( )0.6 (i)0.5 (s)0.5 ( )0.5 (n)0.5 (o)0.5 ( )0.5 (i)0.5 (n)0.5 (f)0.5 (o)0.5 (r)0.5 (m)0.5 (a)-9.4 (t)0.5 (i)0.5 (o)0.5 (n)0.5 ( )0.5 (r)0.5 (e)0.5 (g)0.5 (a)0.5 (r)0.5 (d)0.6 (in)0.6 (g )0.6 (t)0.5 (h)0.5 (e)0.5 ( )0.5 (p)0.5 (r)0.5 (e)0.5 (s)0.5 (e)0.5 (n)0.5 (c)0.5 (e)0.6 ( )0.5 (o)0.5 (f)0.5 ( )0.5 (t)0.5 (h)0.5 (a)0.5 (l)0.5 (i)0.5 (d)0.5 (o)0.6 (m)0.5 (i)0.5 (d)0.5 (e)0.5 ( )0.5 (i)0.5 (n)0.5 ( )0.5 (h)0.5 (u)0.5 (m)0.5 (a)0.5 (n)0.5 ( )0.5 (m)0.6 (i)0.5 (l)0.5 (k)0.5 (,)37.5 ( )0.5 (t)0.5 (h)0.5 (e)0.5 ( )0.5 (e)0.5 (f)0.5 (f)0.6 (e)0.5 (c)0.5 (t)0.5 (s)-19 ( )]TJ -0.008 Tc 0.095 Tw 0 -1.057 Td [(of )37.2 (THALOMID on the breastfed child,)36.8 ( or the effects of )37.2 (THALOMID on milk production.)29 ( )]TJ 0 Tc 0.134 Tw 0 -1.057 Td [(Thalidomide is excreted in the milk of lacta)-10 (ting rabbits )]TJ /T1_1 1 Tf [(\(see Da)-9.9 (ta\))]TJ /T1_0 1 Tf [(.)37.1 ( Because man)-10 (y )]TJ -0.01 Tc 0.086 Tw 0 -1.057 Td [(drugs are excreted in human milk and because of the potential for advers\ e reactions)-10 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.057 Td [(in a breastfed child from )37.4 (THALOMID,)37.3 ( advise women not to breastfeed during trea)-9.7 (tment)-14 ( )]TJ -0.017 Tc 0.011 Tw 0 -1.057 Td (with THALOMID.)Tj 0.017 Tw 0 -1.728 Td [(Da)-9.8 (ta)]TJ /T1_1 1 Tf 0.048 Tw 0 -1.503 Td [(Animal Da)-9.8 (ta)]TJ /T1_0 1 Tf -0.011 Tc 0.076 Tw 0 -1.552 Td [(I)0.5 (n)0.5 ( l)0.5 (a)0.5 (c)0.5 (t)0.6 (a)-9.5 (t)0.5 (i)0.6 (n)0.5 (g)0.5 ( f)0.6 (e)0.5 (m)0.5 (a)0.5 (l)0.6 (e)0.5 ( r)0.5 (a)0.6 (b)0.5 (b)0.5 (i)0.5 (t)0.6 (s)0.5 ( a)-9.5 (t)0.6 ( a)0.5 (n)0.5 ( o)0.5 (r)0.5 (a)0.6 (l)0.5 ( d)0.5 (o)0.5 (s)0.6 (e)0.5 ( o)0.6 (f)0.5 ( 1)0.5 (5)0.6 (0)0.5 ( m)0.5 (g)0.6 (/)0.5 (k)0.5 (g)0.5 (/)0.5 (d)0.5 (a)0.6 (y)55.5 (,)37.5 ( t)0.6 (h)0.5 (e)0.5 ( a)-9.4 (v)0.5 (e)0.5 (r)0.6 (a)-9.5 (g)0.5 (e)0.5 ( t)0.5 (h)0.5 (a)0.5 (l)0.6 (i)0.5 (d)0.5 (o)0.5 (m)0.6 (i)0.5 (d)0.5 (e)-11 ( )]TJ -0.004 Tc 0.114 Tw 0 -1.057 Td [(concentra)-10 (tions in milk ranged from 22 to 36 mcg per mL.)37 ( In the stud)-9.9 (y of lacta)-9.9 (ting)-4 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.057 Td [(female rabbits,)37.2 ( high concentra)-9.7 (tions of thalidomide \(7741 \226 71425 ng per mL\) were)-5 ( )]TJ 0.001 Tc 0.139 Tw 0 -1.057 Td [(noted in milk during four weeks of pre-weaning period.)37.1 ( Milk concentra)-10 (tions were)1 ( )]TJ 0.002 Tc 0.141 Tw 0 -1.057 Td [(1)0.5 (.)0.5 (1)0.5 (6)0.5 ( \226)0.5 ( 2)0.5 (.)0.5 (1)0.5 (1)0.5 (,)37.5 ( 1)0.5 (.)0.5 (0)0.5 (5)0.5 ( \226)0.5 ( 2)0.5 (.)0.5 (4)0.5 (3)0.5 (,)37.5 ( a)0.5 (n)0.5 (d)0.5 ( 0.)0.5 (6)0.6 (4)0.5 ( \226)0.5 ( 3)0.5 (.)0.5 (6)0.5 (3)0.5 ( t)0.5 (i)0.5 (m)0.5 (e)0.5 (s)0.5 ( t)0.6 (h)0.5 (a)-9.5 (t)0.5 ( o)0.6 (f)0.5 ( p)0.5 (l)0.5 (a)0.5 (s)0.5 (m)0.5 (a)0.5 ( a)-9.5 (t)0.5 ( 3)0.5 (0)0.5 (,)37.5 ( 1)0.5 (5)0.5 (0)0.5 ( a)0.5 (n)0.5 (d)2 ( )]TJ -0.001 Tc 0.126 Tw 0 -1.057 Td [(5)0.5 (00)0.5 ( m)0.5 (g/)0.5 (k)0.5 (g t)0.5 (ha)0.5 (li)0.5 (d)0.5 (om)0.5 (id)0.5 (e)0.5 ( d)0.5 (os)0.5 (e)0.5 (s,)37.5 ( r)0.5 (e)0.5 (sp)0.5 (ec)0.5 (t)0.5 (iv)0.5 (e)0.5 (ly)0.5 (; th)0.5 (a)0.5 (li)0.5 (d)0.5 (om)0.5 (id)0.5 (e)0.5 (,)37.4 ( as)0.5 ( a)0.5 ( li)0.5 (p)0.5 (op)0.5 (hi)0.5 (l)0.5 (ic)0.5 ( c)0.5 (om)0.5 (p)0.5 (ou)0.5 (nd)0.5 (,)36 ( )]TJ -0.017 Tc 0.049 Tw 0 -1.057 Td [(distributed )0.5 (into milk,)37.2 ( )0.5 (with )0.5 (concentra)-9.7 (tions )0.5 (a)-9.8 (ttained similar to )0.5 (or slightly )0.5 (higher )0.5 (than )0.5 (those)-17 ( )]TJ 0.048 Tw 0 -1.057 Td [(of systemic concentra)-9.8 (tions.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.886 Td (8.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(F)20.2 (emales and Males of Reproductive P)24.2 (otential)]TJ /T1_0 1 Tf 0.011 Tw -3.375 -1.548 Td [(Pregnanc)20.2 (y T)74.2 (esting)]TJ -0.002 Tc 0.124 Tw 0 -1.552 Td [(THALOMID can cause fetal harm when administered during pregnanc)19.9 (y )]TJ /T1_1 1 Tf [([see Use in)-2 ( )]TJ 0.002 Tc 0.141 Tw 0 -1.057 Td [(Sp)0.5 (eci)0.5 (\037c P)18.5 (opu)0.5 (la)-9.5 (tio)0.5 (ns \()0.5 (8.1)0.5 (\)])]TJ /T1_0 1 Tf [(.)37.5 ( )36.6 (V)18.4 (er)0.5 (ify)0.5 ( th)0.5 (e pr)0.5 (egn)0.5 (anc)20.5 (y st)0.5 (a)-9.6 (t)0.5 (us o)0.5 (f fe)0.5 (ma)0.5 (le)0.5 (s of)0.5 ( rep)0.5 (ro)0.5 (duc)0.5 (tiv)0.5 (e)2 ( )]TJ 0.147 Tw 0 -1.057 Td [(potential )0.5 (prior to initia)-10.4 (ting )37.4 (THALOMID )0.5 (thera)-10.4 (py and )0.5 (during )0.5 (thera)-10.4 (py)54.5 (.)36.6 ( )37.4 (Advise females)2 ( )]TJ 0.001 Tc 0.136 Tw 0 -1.057 Td [(o)0.5 (f)0.6 ( r)0.5 (e)0.6 (p)0.5 (r)0.5 (o)0.6 (d)0.5 (u)0.5 (c)0.6 (t)0.5 (i)0.5 (v)0.6 (e)0.5 ( p)0.5 (o)0.6 (t)0.5 (e)0.5 (n)0.6 (t)0.5 (i)0.5 (a)0.6 (l)0.5 ( t)0.6 (h)0.5 (a)-9.5 (t)0.6 ( t)0.5 (h)0.6 (e)0.5 (y)0.5 ( m)0.6 (u)0.5 (s)0.5 (t)0.6 ( a)-9.5 (v)0.6 (o)0.5 (i)0.5 (d)0.6 ( p)0.5 (r)0.6 (e)0.5 (g)0.5 (n)0.5 (a)0.6 (n)0.5 (c)20.5 (y)0.6 ( 4)0.5 ( w)0.6 (e)0.5 (e)0.5 (k)0.6 (s)0.5 ( b)0.5 (e)0.6 (f)0.5 (o)0.6 (r)0.5 (e)0.5 ( t)0.6 (h)0.5 (e)0.5 (r)0.6 (a)-9.5 (p)0.6 (y)55.5 (,)38 ( )]TJ 0.003 Tc 0.151 Tw 0 -1.057 Td [(while taking )37 (THALOMID,)36.7 ( during dose interruptions and for a)-10.3 (t least 4 weeks after)3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.057 Td [(completing thera)-9.8 (py)55.2 (.)]TJ 0.036 Tw 0 -1.777 Td [(F)24.3 (emales of reproductive potential must ha)-9.7 (ve 2 nega)-9.7 (tive pregnanc)20.2 (y tests before initia)-9.7 (ting)-17 ( )]TJ -0.012 Tc 0.071 Tw 0 -1.057 Td [(T)0.5 (H)0.5 (A)0.5 (L)0.6 (O)0.5 (M)0.5 (I)0.5 (D)0.5 (.)37.5 ( )37 (T)0.6 (h)0.5 (e)0.5 ( \036)0.5 (r)0.6 (s)0.5 (t)0.5 ( t)0.5 (e)0.6 (s)0.5 (t)0.5 ( s)0.5 (h)0.5 (o)0.6 (u)0.5 (l)0.5 (d)0.5 ( b)0.6 (e)0.5 ( p)0.5 (e)0.6 (r)0.5 (f)0.5 (o)0.5 (r)0.5 (m)0.6 (e)0.5 (d)0.5 ( w)0.5 (i)0.6 (t)0.5 (h)0.5 (i)0.5 (n)0.5 ( 1)0.5 (0)0.5 (-)0.5 (1)0.5 (4)0.5 ( d)0.5 (a)0.5 (y)0.5 (s)0.5 (,)37.5 ( a)0.5 (n)0.5 (d)0.5 ( t)0.6 (h)0.5 (e)0.5 ( s)0.5 (e)0.6 (c)0.5 (o)0.5 (n)0.5 (d)0.5 ( t)0.5 (e)0.5 (s)0.5 (t)-12 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.057 Td [(within 24 hours prior to prescribing )36.9 (THALOMID.)37.1 ( Once trea)-9.9 (tment has started and during)-14 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.057 Td [(dose interruptions,)36.9 ( pregnanc)19.9 (y testing for females of reproductive potential should occur)-16 ( )]TJ -0.019 Tc 0.036 Tw 0 -1.057 Td [(weekly during the \036rst 4 weeks of use,)36.7 ( then pregnanc)19.7 (y testing should be repea)-10.2 (ted ever)-18.2 (y)-19 ( )]TJ -0.005 Tc 0.111 Tw 0 -1.057 Td [(4 weeks in females with regular menstrual c)19.7 (yc)19.7 (les.)36.7 ( If menstrual c)19.6 (yc)19.7 (les are irregular)73.7 (,)32 ( )]TJ -0.01 Tc 0.081 Tw 0 -1.057 Td [(t)0.5 (h)0.5 (e)0.5 ( p)0.5 (r)0.5 (e)0.5 (g)0.5 (na)0.5 (n)0.5 (c)20.5 (y)0.5 ( t)0.5 (e)0.5 (s)0.5 (t)0.5 (i)0.5 (n)0.5 (g)0.5 ( sh)0.5 (o)0.5 (u)0.5 (l)0.5 (d)0.5 ( o)0.5 (c)0.5 (c)0.5 (u)0.5 (r)0.5 ( e)0.5 (ve)0.6 (r)-17.5 (y)0.5 ( 2 w)0.5 (e)0.5 (e)0.5 (k)0.5 (s)0.5 (.)37.5 ( P)0.5 (r)0.5 (e)0.5 (g)0.5 (n)0.5 (a)0.5 (n)0.5 (c)20.4 (y)0.5 ( t)0.5 (e)0.5 (s)0.5 (t)0.5 (i)0.5 (n)0.5 (g)0.5 ( a)0.5 (n)0.5 (d)0.5 ( co)0.5 (u)0.5 (n)0.5 (s)0.5 (e)0.5 (l)0.5 (i)0.5 (n)0.5 (g)-10 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.057 Td [(should be performed if a pa)-10 (tient misses her period or if there is an)-10 (y abnormality in her)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.057 Td [(menstrual bleeding.)37.2 ( )37.2 (THALOMID trea)-9.8 (tment must be discontinued during this evalua)-9.8 (tion.)]TJ 0.017 Tw 0 -1.728 Td (Contraception)Tj /T1_1 1 Tf 0 -1.503 Td [(F)24.2 (emales)]TJ /T1_0 1 Tf 0.015 Tc 0.208 Tw 0 -1.552 Td [(F)24.1 (emales of reproductive potential must commit either to abstain continuou\ sly)15 ( )]TJ 0 Tc 0.134 Tw 0 -1.057 Td (from heterosexual sexual intercourse or to use 2 methods of reliable bir\ th control )Tj 0.009 Tc 0.178 Tw 0 -1.057 Td [(simultaneously:)37.1 ( one highly effective form of contraception \226 tubal liga)-9.9 (tion,)37.1 ( IUD,)46 ( )]TJ -0.009 Tc 0.09 Tw 0 -1.057 Td [(hormonal \(birth control pills,)36.7 ( injections,)36.7 ( hormonal pa)-10.2 (tches,)36.7 ( va)-10.2 (ginal rings,)36.8 ( or implants\),)28 ( )]TJ -0.008 Tc 0.092 Tw 0 -1.057 Td [(or partner\222)55.4 (s vasectomy)55.4 (,)37.4 ( a)0.5 (nd 1 additiona)0.5 (l effective contraceptive method \226 male la)-9.6 (tex)-8 ( )]TJ 0.094 Tw 0 -1.057 Td [(or synthetic condom,)36.9 ( dia)-10 (phra)-10 (gm,)36.9 ( or cer)-18.1 (vical ca)-10 (p.)37 ( Contraception must begin 4 weeks)-8 ( )]TJ ET q 1 0 0 1 324 619.5344 cm 0 0 m 24.239 0 l S Q BT -0.01 Tc 0.083 Tw 8 0 0 8 324 727.1403 Tm [(prior to initia)-9.8 (ting trea)-9.7 (tment with )37.3 (THALOMID,)37.3 ( during thera)-9.7 (py)55.2 (,)37.3 ( during dose interruptions,)27 ( )]TJ -0.006 Tc 0.104 Tw 0 -1.044 Td [(and continuing for 4 weeks follo)-10 (wing discontinua)-10 (tion of )36.7 (THALOMID thera)-10 (py)54.9 (.)37 ( Reliable)-6 ( )]TJ -0.021 Tc 0.036 Tw 0 -1.044 Td [(contraception is indica)-9.8 (ted even where there has been a histor)-17.8 (y of infertility)55.2 (,)37.2 ( unless due to)-21 ( )]TJ 0 -1.044 Td [(hysterectomy)54.9 (.)37 ( F)24 (emales of reproductive potential should be referred to a quali\036ed pro\ vider)-21 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(of contraceptive methods,)37.2 ( if needed.)]TJ /T1_1 1 Tf 0.017 Tw 0 -1.716 Td (Males)Tj /T1_0 1 Tf -0.01 Tc 0.086 Tw 0 -1.539 Td [(Thalidomide is present in the semen of males who take )37 (THALOMID.)36.6 ( )37.1 (Therefore,)36.7 ( males)-10 ( )]TJ -0.011 Tc 0.079 Tw 0 -1.044 Td [(must al)-10 (ways use a la)-10 (tex or synthetic condom during an)-10.1 (y sexual contact with females)-11 ( )]TJ 0.078 Tw 0 -1.044 Td [(of reproductive potential while taking )36.8 (THALOMID,)37.2 ( during dose interruptions and for up)-11 ( )]TJ -0.007 Tc 0.099 Tw 0 -1.044 Td [(to 28 days after discontinuing )37 (THALOMID,)37 ( even if they ha)-10 (ve undergone a successful)-7 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(vasectomy)55.2 (.)37.2 ( Male pa)-9.8 (tients taking )37.2 (THALOMID must not dona)-9.8 (te sperm.)]TJ 0.017 Tw 0 -1.716 Td (Infertility)Tj -0.005 Tc 0.106 Tw 0 -1.539 Td [(B)0.5 (a)0.5 (se)0.5 (d)0.5 ( o)0.5 (n \036)0.5 (n)0.5 (di)0.5 (n)0.5 (gs)0.5 ( i)0.5 (n a)0.5 (n)0.5 (im)0.5 (a)0.5 (l)0.5 (s)0.5 (,)37.4 ( m)0.5 (a)0.5 (l)0.5 (e)0.5 ( f)0.5 (e)0.5 (r)0.5 (t)0.5 (il)0.5 (i)0.5 (t)0.5 (y)0.5 ( m)0.5 (a)0.5 (y)0.5 ( be)0.5 ( c)0.5 (o)0.5 (mp)0.5 (r)0.5 (o)0.5 (m)0.5 (is)0.5 (e)0.5 (d)0.5 ( by)0.5 ( t)0.5 (re)0.5 (a)-9.5 (t)0.5 (m)0.5 (e)0.5 (n)0.5 (t w)0.5 (i)0.5 (t)0.5 (h)-5.1 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (THALOMID )Tj /T1_1 1 Tf 0.011 Tw 4.097 0 Td [([see )-36.7 (Nonc)20.2 (linical T)74.2 (oxicolog)]TJ 0.048 Tw 9.098 0 Td (y \(13.1\)])Tj /T1_0 1 Tf 0 Tc 0 Tw (.)Tj /T1_2 1 Tf -0.017 Tc 0.017 Tw -13.195 -1.873 Td (8.4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(P)24.2 (ediatric Use)]TJ /T1_0 1 Tf -0.015 Tc 0.061 Tw -3.375 -1.584 Td [(Safety and effectiveness in pedia)-10.4 (tric pa)-10.4 (tients belo)-10.4 (w the a)-10.4 (ge of 12 years ha)-10.3 (ve not been)-15 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (established.)Tj /T1_2 1 Tf 0 -1.873 Td (8.5)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Geriatric Use)Tj /T1_0 1 Tf 0.01 Tc 0.181 Tw -3.375 -1.584 Td [(O)0.5 (n)0.5 (e)0.5 ( h)0.5 (u)0.5 (nd)0.5 (r)0.5 (e)0.5 (d)0.5 ( a)0.5 (n)0.5 (d)0.5 ( s)0.5 (e)0.5 (v)0.5 (e)0.5 (n)0.5 (t)0.5 (y)0.5 (-)0.5 (s)0.5 (i)0.5 (x)0.5 ( \()0.5 (5)0.5 (2)0.5 (%)0.5 (\))0.5 ( o)0.5 (f)0.5 ( 3)0.5 (3)0.5 (6)0.5 ( p)0.5 (a)-9.5 (t)0.6 (ie)0.6 (nt)0.5 (s)0.5 ( t)0.5 (r)0.5 (e)0.5 (a)-9.5 (t)0.5 (e)0.5 (d)0.5 ( w)0.5 (i)0.5 (t)0.5 (h)0.5 ( )37 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (OM)0.5 (I)0.5 (D)0.5 ( i)0.5 (n)10 ( )]TJ -0.013 Tc 0.066 Tw 0 -1.044 Td [(c)0.5 (o)0.5 (m)0.5 (b)0.5 (i)0.5 (n)0.5 (a)-9.4 (t)0.5 (i)0.5 (o)0.5 (n)0.5 ( w)0.5 (i)0.5 (t)0.5 (h)0.5 ( d)0.5 (e)0.5 (x)0.5 (a)0.5 (m)0.5 (e)0.5 (t)0.6 (h)0.5 (a)0.5 (s)0.5 (o)0.5 (n)0.5 (e)0.5 ( w)0.5 (e)0.5 (r)0.5 (e)0.5 ( \037)0.5 (6)0.5 (5)0.5 ( o)0.5 (f)0.6 ( a)-9.4 (g)0.5 (e)0.5 ( w)0.5 (h)0.5 (i)0.5 (l)0.5 (e)0.5 ( 5)0.5 (0)0.5 ( \()0.5 (1)0.5 (5)0.5 (%)0.5 (\))0.5 ( w)0.5 (e)0.5 (r)0.5 (e)0.5 ( \037)0.5 (7)0.5 (5)0.5 (.)37.5 ( P)18.5 (a)-9.4 (t)0.5 (i)0.5 (e)0.5 (n)0.5 (t)0.5 (s)-13 ( )]TJ -0.008 Tc 0.097 Tw 0 -1.044 Td [(\03765 years of a)-10.4 (ge on Stud)-10.4 (y 2 had higher incidences of a)-10.4 (trial \036brilla)-10.5 (tion,)36.5 ( constipa)-10.4 (tion,)29 ( )]TJ 0.001 Tc 0.139 Tw 0 -1.044 Td [(fa)-10 (tigue,)37 ( nausea,)37 ( hypokalemia,)37 ( deep venous thrombosis,)37 ( hyperglycemia,)37 ( pulmonar)-18 (y)1 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(embolism,)37.2 ( and asthenia compared to pa)-9.8 (tients <65.)]TJ /T1_2 1 Tf 0.017 Tw 0 -2.048 Td (9)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(DR)-9.8 (UG ABUSE AND DEPENDENCE)]TJ /T1_0 1 Tf 0.004 Tc 0.156 Tw -3.375 -1.719 Td [(Physical )0.5 (and )0.5 (psychological )0.5 (dependence )0.5 (has )0.5 (not )0.5 (been reported )0.5 (in )0.5 (pa)-10.2 (tients taking)4 ( )]TJ 0.006 Tc 0.164 Tw 0 -1.044 Td [(THALOMID; ho)-9.9 (wever)74.1 (,)37 ( as with other tranquilizers/hypnotics,)37 ( thalidomide has been)5.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(reported to result in habitua)-9.8 (tion to its sopori\036c effects.)]TJ /T1_2 1 Tf 0.017 Tw 0 -2.048 Td (10)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (OVERDOSAGE)Tj /T1_0 1 Tf -0.007 Tc 0.097 Tw -3.375 -1.719 Td [(There is no speci\036c antidote for a )37 (THALOMID overdose.)37.3 ( In the event of an overdose,)30 ( )]TJ -0.011 Tc 0.079 Tw 0 -1.044 Td [(the pa)-10 (tient\222)55 (s vital signs should be monitored and a)-10 (ppropria)-10 (te supportive care given to)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(maintain blood pressure and respira)-9.7 (tor)-17.8 (y sta)-9.8 (tus.)]TJ /T1_2 1 Tf 0.017 Tw 0 -2.048 Td (11)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (DESCRIPTION)Tj /T1_0 1 Tf -0.02 Tc 0.02 Tw -3.375 -1.719 Td [(THALOMID,)37.3 ( )]TJ /C2_0 1 Tf 0 Tc 0 Tw 4.24 0 Td <005F>Tj /T1_0 1 Tf -0.02 Tc 0.036 Tw 0.61 0 Td [(-\(N-phthalimido\) glutarimide,)37.3 ( is an immunomodula)-9.7 (tor)-17.7 (y a)-9.7 (gent.)37.3 ( )37.3 (The empirical)-20 ( )]TJ 0.007 Tc 0.168 Tw -4.85 -1.044 Td (formula for thalidomide is C)Tj -0.007 Tw 5.6 0 0 5.6 412.7922 370.3329 Tm (13)Tj 0 Tc 0 Tw 8 0 0 8 418.2447 370.5728 Tm (H)Tj 0.007 Tc -0.007 Tw 5.6 0 0 5.6 422.5953 370.3329 Tm (10)Tj 0 Tc 0 Tw 8 0 0 8 428.0479 370.5728 Tm (N)Tj 5.6 0 0 5.6 432.5506 370.3329 Tm (2)Tj 8 0 0 8 435.2769 370.5728 Tm (O)Tj 5.6 0 0 5.6 439.7795 370.3329 Tm (4)Tj 0.007 Tc 0.168 Tw 8 0 0 8 442.5058 370.5728 Tm [( and the gram molecular weight is 258.2.)44 ( )]TJ 0 Tc 0 Tw 16.687 0 Td ( )Tj -0.017 Tc 0.048 Tw -31.5 -1.044 Td (The CAS number of thalidomide is 50-35-1.)Tj ET /PlacedGraphic /MC0 BDC EMC q 324 259.186 252 94.111 re W n 0.704 w /GS0 gs q 1 0 0 1 410.4932 319.8298 cm 0 0 m -12.066 -7.228 l -12.066 -21.967 l 0 -28.837 l 12.049 -21.967 l 12.049 -7.228 l 12.049 -7.183 l 0 0 l h 10.364 -14.57 m 10.364 -20.377 5.656 -25.085 -0.15 -25.085 c -5.957 -25.085 -10.665 -20.377 -10.665 -14.57 c -10.665 -8.764 -5.957 -4.056 -0.15 -4.056 c 5.656 -4.056 10.364 -8.764 10.364 -14.57 c h 30.544 -18.062 m 24.791 -26.063 l 12.049 -21.967 l 12.049 -7.228 l 24.106 -2.442 l 30.579 -11.215 l 70.93 -5.859 m 75.645 -12.944 l 76.727 -14.57 l 69.685 -26.601 l 55.013 -26.406 l 47.58 -14.375 l 55.062 -1.709 l 66.92 -1.709 l 88.489 -13.103 m 75.553 -13.103 l 88.489 -15.255 m 76.238 -15.255 l 48.55 7.333 m 54.622 -2.149 l 50.025 8.268 m 56.383 -1.66 l 26.847 8.176 m 23.226 -2.736 l 28.827 7.661 m 25.084 -3.616 l 22.981 -25.28 m 27.388 -37.352 l 25.329 -25.036 m 29.534 -36.555 l S Q Q BT /GS0 gs /T1_3 1 Tf 0 Tc 0 Tw 9.0128 0 0 9.0128 478.028 321.6221 Tm (H)Tj 0 -0.778 Td (N)Tj -4.094 -1.383 Td (N)Tj -0.509 2.898 Td (O)Tj 0.073 -5.839 Td (O)Tj 2.085 5.839 Td (O)Tj 4.812 -2.895 Td (O)Tj ET q 324 259.186 252 94.111 re W n 0.704 w q 1 0 0 1 458.0735 305.4549 cm 0 0 m -11.511 0 l S Q BT 9.0128 0 0 9.0128 387.9789 345.8168 Tm (Chemical Structure of Thalidomide)Tj ET Q q 387.979 259.186 124.042 94.111 re W n 0.451 w q 1 0 0 1 387.9789 344.9158 cm 0 0 m 0 0 l 124.042 0 l h S Q Q q 324 259.186 252 94.111 re W n BT /T1_4 1 Tf -0.01 Tc 0.01 Tw 9.0128 0 0 9.0128 393.0357 261.0979 Tm (Note:)Tj 0 Tw 1.856 0 Td ( \225 = asymmetric carbon atom)Tj ET Q BT /GS1 gs /T1_0 1 Tf -0.017 Tc 0.038 Tw 8 0 0 8 324 244.1916 Tm [(Thalidomide is an off-white to white,)37.2 ( odorless,)37.2 ( cr)-17.7 (ystalline po)-9.8 (wder tha)-9.8 (t is soluble a)-9.8 (t 25\260C)-17 ( )]TJ 0.05 Tw 0 -1.044 Td [(in dimethyl sulfoxide and sparingly soluble in wa)-9.8 (ter and ethanol.)37.2 ( )37 (The glutarimide moiety)-17 ( )]TJ -0.014 Tc 0.067 Tw 0 -1.044 Td [(contains )0.5 (a )0.5 (single asymmetric )0.5 (center and,)36.6 ( therefore,)36.6 ( )0.5 (may )0.5 (exist )0.5 (in )0.5 (either )0.5 (of )0.5 (two )0.5 (optically)-14 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.044 Td [(active forms designa)-9.8 (ted S-\(-\) or R-\()]TJ 0 Tc 0 Tw 13.04 0.125 Td (+)Tj -0.012 Tc 0.073 Tw 0.588 -0.125 Td [(\).)37.2 ( )37 (THALOMID is an equal mixture of the S-\(-\) and)-12 ( )]TJ -0.017 Tc 0.017 Tw -13.628 -1.044 Td (R-\()Tj 0 Tc 0 Tw 1.06 0.125 Td (+)Tj -0.017 Tc 0.048 Tw 0.583 -0.125 Td [(\) forms and,)37.2 ( therefore,)37.2 ( has a net optical rota)-9.7 (tion of zero.)]TJ 0 Tc 0.131 Tw -1.643 -1.764 Td [(T)0.5 (H)0.5 (AL)0.5 (O)0.5 (MI)0.5 (D)0.5 ( is)0.5 ( a)-9.5 (v)0.5 (ai)0.5 (l)0.5 (a)0.5 (bl)0.5 (e)0.5 ( i)0.5 (n 5)0.5 (0)0.5 ( m)0.5 (g,)37.5 ( 1)0.5 (00)0.5 ( m)0.5 (g)0.5 (,)37.4 ( 1)0.5 (5)0.5 (0 m)0.5 (g)0.5 ( a)0.5 (nd)0.5 ( 2)0.5 (0)0.5 (0 m)0.5 (g)0.5 ( c)0.5 (a)-9.5 (ps)0.5 (u)0.5 (le)0.5 (s)0.5 ( f)0.5 (or)0.5 ( o)0.5 (r)0.5 (al )]TJ -0.015 Tc 0.06 Tw 0 -1.044 Td [(administra)-9.8 (tion.)37.2 ( )37.2 (Active ingredient:)37.2 ( thalidomide.)37.2 ( Inactive ingredients:)37.2 ( pregela)-9.8 (tinized starch)-15 ( )]TJ -0.021 Tc 0.036 Tw 0 -1.044 Td [(and ma)-9.8 (gnesium steara)-9.8 (te.)37.1 ( )37.2 (The 50 mg ca)-9.8 (psule shell contains gela)-9.9 (tin,)37.2 ( titanium dioxide,)37.2 ( and)-21 ( )]TJ -0.02 Tc 0 -1.044 Td [(black ink.)37.3 ( )37.3 (The 100 mg ca)-9.7 (psule shell contains black iron oxide,)37.3 ( yello)-9.7 (w iron oxide,)37.3 ( titanium)-20 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.044 Td [(dioxide,)36.7 ( gela)-10.3 (tin,)36.7 ( and black ink.)36.7 ( )36.7 (The 150 mg ca)-10.3 (psule shell contains FD&C blue #2,)36.7 ( black)-16 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.044 Td [(iron oxide,)37.2 ( yello)-9.7 (w iron oxide,)37.3 ( titanium dioxide,)37.2 ( gela)-9.7 (tin,)37.3 ( and black and white ink.)37.3 ( )36.6 (The)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(200 mg ca)-9.8 (psule shell contains FD&C blue #2,)37.2 ( titanium dioxide,)37.2 ( gela)-9.8 (tin,)37.2 ( and white ink.)]TJ /T1_2 1 Tf 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thrombophlebitis,)37.2 ( thrombosis.)]TJ /T1_0 1 Tf 0.002 Tc 0.146 Tw 0 -1.764 Td (Digestive System:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.59 0 Td [(Cholangitis,)36.6 ( cholesta)-10.4 (tic jaundice,)36.6 ( colitis,)36.6 ( d)-10.4 (yspepsia,)36.6 ( d)-10.4 (yspha)-10.4 (gia,)39 ( )]TJ -0.012 Tc 0.071 Tw -7.59 -1.044 Td [(e)0.5 (so)0.5 (ph)0.5 (a)-9.5 (gi)0.5 (ti)0.5 (s,)37.5 ( g)0.5 (a)0.5 (st)0.5 (ro)0.5 (e)0.5 (nt)0.5 (er)0.5 (i)0.5 (ti)0.5 (s,)37.5 ( ga)0.5 (st)0.5 (r)0.5 (oi)0.5 (nt)0.5 (es)0.5 (t)0.5 (in)0.5 (al)0.5 ( di)0.5 (so)0.5 (rd)0.5 (er)74.5 (,)37.5 ( g)0.5 (as)0.5 (t)0.5 (ro)0.5 (in)0.5 (te)0.5 (s)0.5 (ti)0.5 (na)0.5 (l)0.5 ( h)0.5 (e)0.5 (mo)0.5 (rr)0.5 (h)0.5 (a)-9.6 (g)0.5 (e,)37.5 ( gum)-11.9 ( )]TJ -0.001 Tc 0.126 Tw 0 -1.044 Td [(d)0.5 (i)0.6 (s)0.5 (o)0.5 (r)0.6 (d)0.5 (e)0.6 (r)74.5 (,)37.5 ( h)0.6 (e)0.5 (p)0.5 (a)-9.4 (t)0.5 (i)0.6 (t)0.5 (i)0.5 (s)0.6 (,)37.5 ( p)0.5 (a)0.6 (n)0.5 (c)0.5 (r)0.6 (e)0.5 (a)-9.4 (t)0.5 (i)0.5 (t)0.6 (i)0.5 (s)0.5 (,)37.6 ( p)0.5 (a)0.6 (r)0.5 (o)0.6 (t)0.5 (i)0.5 (d)0.6 ( g)0.5 (l)0.5 (a)0.6 (n)0.5 (d)0.6 ( e)0.5 (n)0.5 (l)0.6 (a)0.5 (r)0.6 (g)0.5 (e)0.5 (m)0.6 (e)0.5 (n)0.5 (t)0.6 (,)37.5 ( p)0.6 (e)0.5 (r)0.5 (i)0.6 (o)0.5 (d)0.6 (o)0.5 (n)0.5 (t)0.6 (i)0.5 (t)0.6 (i)0.5 (s)0.5 (,)37.5 ( s)0.5 (t)0.5 (o)0.6 (m)0.5 (a)-9.4 (t)0.5 (i)0.5 (t)0.6 (i)0.5 (s)0.5 (,)36 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(tongue discolora)-9.8 (tion,)37.2 ( tooth disorder)74.2 (.)]TJ /T1_0 1 Tf -0.026 Tc 0.027 Tw 0 -1.764 Td (Metabolic and Endocrine:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 9.768 0 Td [(Avitaminosis,)36.8 ( bilirubinemia,)36.8 ( dehydra)-10.1 (tion,)36.8 ( hypercholesterolemia,)11 ( )]TJ 0 Tc 0 Tw 21.732 0 Td ( )Tj 0.003 Tc 0.15 Tw -31.5 -1.044 Td [(hypoglycemia,)36.9 ( increased alkaline phospha)-10.1 (tase,)36.9 ( increased lipase,)36.9 ( increased serum)3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(crea)-9.7 (tinine,)37.2 ( peripheral edema.)]TJ /T1_0 1 Tf 0 -1.764 Td (Muscular Skeletal:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.437 0 Td [(My)-9.8 (algia,)37.2 ( my)-9.8 (asthenia.)]TJ /T1_0 1 Tf 0.015 Tc 0.211 Tw -7.437 -1.764 Td [(Ner)-18.3 (vous System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.413 0 Td [(Abnormal gait,)36.6 ( a)-10.4 (taxia,)36.6 ( decreased libido,)36.7 ( decreased reflexes,)52 ( )]TJ -0.013 Tc 0.07 Tw -7.413 -1.044 Td [(dementia,)36.9 ( )0.5 (d)-10 (ysesthesia,)36.9 ( )0.5 (d)-10 (yskinesia,)36.9 ( )0.6 (emotional )0.6 (lability)54.9 (,)36.9 ( )0.6 (hostility)54.9 (,)36.9 ( )0.6 (hypalgesia,)36.9 ( )0.6 (hyperkinesia,)24 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(incoordina)-9.8 (tion,)37.2 ( meningitis,)37.2 ( neurologic disorder)74.2 (,)37.2 ( tremor)74.2 (,)37.2 ( vertigo.)]TJ /T1_0 1 Tf -0.022 Tc 0.036 Tw 0 -1.764 Td [(Respirator)-18.2 (y System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.889 0 Td [(A)-10.2 (pnea,)36.8 ( bronchitis,)36.8 ( lung disorder)73.7 (,)36.8 ( lung edema,)36.7 ( pneumonia \(inc)19.8 (luding)-22 ( )]TJ -0.017 Tc 0.048 Tw -7.889 -1.044 Td [(Pneumoc)20.2 (ystis carinii pneumonia\),)37.2 ( rhinitis.)]TJ /T1_0 1 Tf 0.02 Tc 0.231 Tw 0 -1.764 Td [(S)0.6 (k)0.5 (i)0.5 (n)0.6 ( a)0.5 (n)0.6 (d)0.5 ( A)0.6 (p)0.5 (p)0.5 (e)0.6 (n)0.5 (d)0.6 (a)0.5 (g)0.6 (e)0.5 (s)0.6 (:)]TJ /T1_1 1 Tf /Span<>> BDC 9.719 0 Td ( )Tj EMC 0.316 0 Td [(A)0.5 (n)0.6 (g)0.5 (i)0.6 (o)0.6 (e)0.5 (d)0.6 (e)0.5 (m)0.6 (a)0.5 (,)37.6 ( b)0.5 (e)0.6 (n)0.5 (i)0.6 (g)0.5 (n)0.6 ( s)0.5 (k)0.6 (i)0.5 (n)0.6 ( n)0.6 (e)0.6 (o)0.5 (p)0.6 (l)0.5 (a)0.6 (s)0.5 (m)0.6 (,)37.5 ( e)0.6 (c)0.5 (z)0.6 (e)0.5 (m)0.6 (a)0.6 (,)37.5 ( h)0.5 (e)0.6 (r)0.5 (p)0.6 (e)0.6 (s)20 ( )]TJ -0.011 Tc 0.08 Tw -10.034 -1.044 Td [(simplex,)36.9 ( incomplete Stevens-Johnson syndrome,)36.9 ( nail disorder)73.9 (,)36.9 ( pruritus,)36.9 ( psoriasis,)36.8 ( )0.5 (skin)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(discolora)-9.8 (tion,)37.2 ( skin disorder)74.2 (.)]TJ /T1_0 1 Tf 0.008 Tc 0.176 Tw 0 -1.764 Td (Special Senses:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.861 0 Td [(Conjunctivitis,)36.7 ( eye disorder)73.7 (,)36.7 ( lacrima)-10.3 (tion disorder)73.7 (,)36.7 ( retinitis,)36.7 ( taste)8.1 ( )]TJ -0.017 Tc 0.017 Tw -6.861 -1.044 Td [(per)-17.7 (version.)]TJ /T1_0 1 Tf 0 -1.873 Td (6.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(P)24.2 (ostmarketing Experience)]TJ /T1_1 1 Tf -0.007 Tc 0.099 Tw -3.375 -1.584 Td [(The follo)-10 (wing additional adverse reactions ha)-10 (ve been identi\036ed during post a)-10 (pproval)-7 ( )]TJ -0.017 Tc 0.046 Tw 0 -1.044 Td [(use of )36.8 (THALOMID and are not alread)-9.8 (y inc)20.2 (luded in Clinical )36.8 (T)74.2 (rials Experience )]TJ /T1_2 1 Tf 0.009 Tw [([see Adverse)-17 ( )]TJ -0.012 Tc 0.072 Tw 0 -1.044 Td (Reactions \(6.1\)])Tj /T1_1 1 Tf [(.)37.3 ( Because these reactions are reported voluntarily from a popula)-9.7 (tion of)-12 ( )]TJ -0.018 Tc 0.036 Tw 0 -1.044 Td [(uncertain size,)37.1 ( it is not al)-10 (ways possible to reliably estima)-9.9 (te their frequenc)20.1 (y or establish a)-18 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(causal rela)-9.8 (tionship to drug exposure.)]TJ /T1_0 1 Tf 0 -1.764 Td [(Blood )0.5 (and L)37.2 (ymphatic:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 8.633 0 Td [(Decreased white blood cell )0.5 (counts )0.5 (inc)20.2 (luding febrile neutropenia,)20 ( )]TJ -0.006 Tc 0.105 Tw -8.633 -1.044 Td [(changes in prothrombin time,)36.8 ( panc)19.9 (ytopenia,)36.9 ( chronic myelogenous leukemia,)36.8 ( nodular)-6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(sc)20.2 (lerosing Hodgkin\222)55.3 (s disease,)37.3 ( er)-17.8 (ythroleukemia,)37.1 ( lymphedema,)37.2 ( lymphopenia.)]TJ /T1_0 1 Tf 0 -1.764 Td (Body as a Whole:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.974 0 Td (Hangover effect)Tj /T1_0 1 Tf 0.018 Tc 0.224 Tw -6.974 -1.764 Td [(Cardio)-10 (v)16 (ascular System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 10.326 0 Td [(Sick sinus syndrome,)37 ( EKG abnormalities,)37 ( pulmonar)-18 (y)18.1 ( )]TJ -0.017 Tc 0.017 Tw -10.326 -1.044 Td (hypertension.)Tj /T1_0 1 Tf 0.012 Tc 0.192 Tw 0 -1.764 Td (Digestive System:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.802 0 Td [(Intestinal perfora)-9.6 (tion,)37.4 ( gastrointestinal perfora)-9.6 (tions,)37.3 ( bile duct)12 ( )]TJ -0.017 Tc 0.048 Tw -7.802 -1.044 Td [(obstruction,)37.2 ( stomach ulcer)74.3 (,)37.1 ( a)-9.8 (phthous,)37.2 ( stoma)-9.8 (titis.)]TJ /T1_0 1 Tf 0 -1.764 Td (Ear and Labyrinthine Disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 12.434 0 Td (Hearing impairment.)Tj /T1_0 1 Tf 0.011 Tc 0.19 Tw -12.434 -1.764 Td (Immune System Disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 11.685 0 Td [(Hypersensitivity inc)19.8 (luding ana)-10.2 (phylaxis,)36.8 ( solid organ)11 ( )]TJ -0.017 Tc 0.048 Tw -11.685 -1.044 Td (transplant rejection.)Tj /T1_0 1 Tf -0.019 Tc 0.036 Tw 0 -1.764 Td (Infections and infestations:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 10.675 0 Td [(Severe infections \(e.g.,)37 ( fa)-10 (tal sepsis inc)20 (luding septic shock\),)18 ( )]TJ -0.009 Tc 0.088 Tw -10.675 -1.044 Td [(viral infections \(inc)20.1 (luding varicella zoster virus,)37.2 ( c)20.1 (ytomegalovirus,)37.1 ( and hepa)-9.9 (titis B virus)-9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(reactiva)-9.8 (tion\) and progressive multifocal leukoencephalopa)-9.8 (thy \(PML\).)]TJ /T1_0 1 Tf -0.021 Tc 0.036 Tw 0 -1.764 Td (Metabolic and Endocrine:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 9.951 0 Td [(Electrolyte imbalance inc)19.7 (luding hypercalcemia,)36.7 ( hypona)-10.3 (tremia)-21 ( )]TJ -0.002 Tc 0.123 Tw -9.951 -1.044 Td [(and hypoma)-9.8 (gnesemia,)37.2 ( hypothyroidism,)37.2 ( increased alkaline phospha)-9.8 (tase,)37.2 ( tumor lysis)-2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(syndrome,)37.2 ( myxedema.)]TJ /T1_0 1 Tf 0.004 Tc 0.155 Tw 0 -1.764 Td [(Ner)-18.2 (vous System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.215 0 Td [(Changes in mental sta)-10.1 (tus or mood inc)19.8 (luding suicide a)-10.2 (ttempts,)41 ( )]TJ 0.001 Tc 0.137 Tw -7.215 -1.044 Td [(disturbances in consciousness inc)20.4 (luding letharg)-9.7 (y)55.4 (,)37.3 ( loss of consciousness or stupor)74.3 (,)38 ( )]TJ -0.009 Tc 0.091 Tw 0 -1.044 Td [(seizures inc)19.7 (luding grand mal convulsions and sta)-10.3 (tus epilepticus,)36.7 ( P)17.7 (arkinson\222)54.7 (s disease,)28 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(stroke,)37.2 ( carpal tunnel,)37.2 ( Raynaud\222)55.2 (s syndrome,)37.2 ( migraine,)37.2 ( foot drop.)]TJ /T1_0 1 Tf 0 -1.764 Td [(Renal and Urinar)-17.8 (y Disorders:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 11.357 0 Td [(Renal failure,)37.1 ( acute renal failure,)37.2 ( oliguria,)37.2 ( enuresis.)]TJ /T1_0 1 Tf 0.011 Tc 0.191 Tw -11.357 -1.764 Td (Reproductive System and Breast Disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 18.798 0 Td [(amenorrhea,)36.6 ( sexual d)-10.4 (ysfunction,)48 ( )]TJ -0.017 Tc 0.048 Tw -18.798 -1.044 Td [(galactorrhea,)37.2 ( g)-9.8 (ynecomastia,)37.2 ( metrorrha)-9.8 (gia.)]TJ /T1_0 1 Tf 0 -1.764 Td [(Respirator)-17.8 (y System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 8.029 0 Td [(Pleural effusion,)37.2 ( interstitial lung disease.)]TJ /T1_0 1 Tf -0.001 Tc 0.13 Tw -8.029 -1.764 Td [(Skin )0.5 (and )0.6 (Appendages:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 9.44 0 Td [(Er)-18 (ythema )0.6 (multiforme,)36.9 ( )0.5 (er)-18.1 (ythema )0.5 (nodosum,)36.9 ( )0.5 (toxic )0.5 (epidermal)-1 ( )]TJ 0 Tc 0.131 Tw -9.44 -1.044 Td [(n)0.5 (e)0.5 (cr)0.5 (o)0.5 (l)0.5 (y)0.5 (si)0.5 (s)0.5 ( \()0.5 (T)0.5 (EN)0.5 (\))0.5 (,)37.5 ( d)0.5 (ru)0.5 (g)0.5 ( r)0.5 (e)0.5 (a)0.5 (c)0.5 (ti)0.5 (o)0.5 (n)0.5 ( w)0.5 (i)0.5 (t)0.5 (h eo)0.5 (s)0.5 (i)0.5 (n)0.5 (op)0.5 (h)0.5 (i)0.5 (li)0.5 (a)0.5 ( a)0.5 (n)0.5 (d)0.5 ( s)0.5 (y)0.5 (st)0.5 (e)0.5 (m)0.5 (i)0.5 (c)0.5 ( s)0.5 (ym)0.5 (p)0.5 (t)0.5 (o)0.5 (m)0.5 (s \(D)0.5 (R)0.5 (E)0.5 (SS)0.5 (\))0.5 (,)37 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(purpura,)37.2 ( petechiae.)]TJ /T1_0 1 Tf 0 -1.764 Td (Special Senses:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.325 0 Td [(Diplopia,)37.2 ( n)-9.8 (ysta)-9.8 (gmus)]TJ ET 0.5 w q 1 0 0 1 324 220.4165 cm 0 0 m 83.173 0 l S Q q 1 0 0 1 324 161.3206 cm 0 0 m 41.95 0 l S Q BT /T1_0 1 Tf 0.017 Tw 8 0 0 8 324 727.2481 Tm (7)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(DR)-9.8 (UG INTERACTIONS)]TJ 0.017 Tw -3.375 -1.648 Td (7.1)Tj /Span<>> BDC ( )Tj EMC -0.003 Tc 0.12 Tw 3.375 0 Td [(Opioids,)36.8 ( Antihistamines,)36.9 ( Antipsychotics,)36.8 ( Anti-anxiety Agents,)36.9 ( or Other)-2.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.063 Td [(CNS Depressants \(Inc)20.2 (luding Alcohol\))]TJ /T1_1 1 Tf -0.006 Tc 0.105 Tw -3.375 -1.584 Td [(The use of opioids,)36.9 ( antihistamines,)36.9 ( antipsychotics,)36.9 ( anti-anxiety a)-10.1 (gents,)36.9 ( or other CNS)-6 ( )]TJ -0.011 Tc 0.076 Tw 0 -1.044 Td [(d)0.5 (e)0.5 (p)0.5 (r)0.5 (e)0.5 (s)0.5 (sa)0.6 (nt)0.5 (s)0.5 ( co)0.5 (n)0.5 (c)0.5 (o)0.5 (m)0.5 (i)0.5 (t)0.5 (a)0.5 (n)0.5 (t)0.5 (l)0.5 (y)0.5 ( w)0.5 (i)0.5 (t)0.5 (h)0.5 ( )36.9 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.5 (ID)0.5 ( m)0.5 (a)0.5 (y)0.5 ( c)0.5 (a)0.5 (u)0.5 (s)0.5 (e)0.5 ( a)0.5 (n)0.5 ( a)0.5 (d)0.5 (d)0.5 (i)0.5 (t)0.5 (i)0.5 (v)0.5 (e)0.5 ( s)0.5 (e)0.5 (d)0.5 (a)-9.5 (t)0.5 (i)0.5 (v)0.5 (e)0.5 ( e)0.5 (f)0.5 (f)0.5 (e)0.5 (c)0.5 (t)0.5 ( a)0.5 (n)0.5 (d)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(should be a)-9.8 (voided.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.738 Td (7.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Drugs which Cause Bradycardia)Tj /T1_1 1 Tf -0.008 Tc 0.096 Tw -3.375 -1.584 Td [(The use of drugs which slo)-10.4 (w cardiac conduction concomitantly with )36.7 (THALOMID may)-7.9 ( )]TJ -0.011 Tc 0.082 Tw 0 -1.044 Td [(cause )0.5 (an )0.6 (additive )0.6 (brad)-10.4 (ycardic )0.6 (effect )0.5 (and )0.5 (should )0.6 (be )0.6 (used )0.5 (with )0.5 (caution.)36.6 ( )0.5 (Cardiovascular)-11 ( )]TJ 0 Tc 0.131 Tw 0 -1.044 Td [(m)0.5 (e)0.5 (d)0.5 (ic)0.5 (a)-9.5 (t)0.5 (i)0.5 (o)0.5 (n)0.5 (s)0.5 ( wh)0.5 (i)0.5 (c)0.5 (h)0.5 ( m)0.5 (a)0.5 (y)0.5 ( c)0.5 (a)0.5 (us)0.5 (e)0.5 ( b)0.5 (r)0.5 (a)0.5 (d)-9.6 (y)0.5 (c)0.5 (a)0.5 (r)0.5 (d)0.5 (i)0.5 (a)0.5 ( i)0.5 (n)0.5 (c)20.5 (lu)0.5 (d)0.5 (e)0.5 ( c)0.5 (a)0.5 (l)0.5 (ci)0.5 (u)0.5 (m)0.5 ( c)0.5 (ha)0.5 (n)0.5 (n)0.5 (e)0.5 (l)0.5 ( b)0.5 (l)0.5 (o)0.5 (c)0.5 (k)0.5 (e)0.5 (r)0.5 (s,)37.5 ( b)0.5 (e)0.5 (t)0.5 (a )]TJ -0.002 Tc 0.126 Tw 0 -1.044 Td [(blockers,)36.6 ( alpha/beta-adrenergic blockers,)36.6 ( and digoxin.)36.6 ( Non-cardiac drugs tha)-10.4 (t may)-2 ( )]TJ -0.007 Tc 0.098 Tw 0 -1.044 Td [(cause brad)-9.7 (ycardia inc)20.2 (lude H2 blockers \(e.g.,)37.2 ( famotidine,)37.2 ( cimetidine\),)37.2 ( lithium,)37.2 ( tric)20.2 (yc)20.2 (lic)-7 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(antidepressants and neuromuscular blockers \(succin)-9.8 (ylcholine\).)]TJ -0.007 Tc 0.096 Tw 0 -1.719 Td [(I)0.5 (n)0.5 ( 1)0.5 (6 h)0.5 (e)0.5 (a)0.5 (l)0.5 (t)0.5 (h)0.5 (y)0.5 ( m)0.5 (e)0.5 (n)0.5 (,)37.5 ( t)0.5 (h)0.5 (e)0.5 ( ph)0.5 (a)0.5 (r)0.5 (m)0.6 (a)0.5 (co)0.6 (k)0.5 (i)0.5 (n)0.5 (e)0.5 (t)0.5 (i)0.5 (c)0.5 ( p)0.5 (r)0.5 (o)0.5 (\036)0.5 (l)0.5 (e)0.5 ( o)0.5 (f)0.5 ( a)0.5 ( s)0.5 (i)0.5 (ng)0.6 (l)0.5 (e 0)0.5 (.)0.5 (5)0.5 ( m)0.5 (g)0.5 ( d)0.5 (i)0.5 (g)0.5 (o)0.5 (xi)0.6 (n d)0.5 (o)0.5 (s)0.5 (e)0.5 ( w)0.5 (a)0.5 (s)-7 ( )]TJ -0.001 Tc 0.131 Tw 0 -1.044 Td [(similar with and without the coadministra)-10.3 (tion of )37.2 (THALOMID 200 mg/day a)-10.3 (t stead)-10.3 (y)-1 ( )]TJ -0.013 Tc 0.066 Tw 0 -1.044 Td [(s)0.5 (ta)-9.5 (t)0.5 (e)0.5 ( l)0.5 (e)0.5 (v)0.5 (e)0.5 (ls)0.5 (.)37.4 ( )36.8 (T)0.5 (he)0.5 ( s)0.5 (in)0.5 (g)0.5 (le)0.5 ( d)0.5 (os)0.5 (e)0.5 ( of)0.5 ( d)0.5 (ig)0.5 (o)0.5 (xi)0.5 (n)0.5 ( ha)0.5 (d)0.5 ( n)0.5 (o)0.5 ( ef)0.5 (f)0.5 (e)0.5 (ct)0.5 ( o)0.5 (n t)0.5 (h)0.5 (e p)0.5 (h)0.5 (ar)0.5 (m)0.5 (a)0.5 (co)0.5 (k)0.5 (in)0.5 (e)0.5 (t)0.5 (ic)0.5 ( pr)0.5 (o)0.5 (\036)0.5 (le)0.5 ( o)0.5 (f)-13 ( )]TJ -0.015 Tc 0.061 Tw 0 -1.044 Td [(THALOMID.)36.6 ( )36.9 (The safety of long-term concomitant use of )36.9 (THALOMID and digoxin has not)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(been evalua)-9.8 (ted.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.738 Td (7.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Drugs which Cause P)24.2 (eripheral Neuropathy)]TJ /T1_1 1 Tf -0.005 Tc 0.106 Tw -3.375 -1.584 Td [(T)0.5 (h)0.5 (e)0.5 ( u)0.5 (s)0.5 (e)0.6 ( o)0.5 (f)0.5 ( d)0.5 (r)0.5 (u)0.5 (g)0.5 (s)0.5 ( w)0.5 (h)0.5 (ic)0.6 (h)0.5 ( c)0.5 (a)0.5 (u)0.5 (s)0.5 (e)0.5 ( p)0.5 (e)0.6 (r)0.5 (i)0.5 (p)0.5 (h)0.5 (e)0.5 (r)0.5 (a)0.5 (l)0.5 ( n)0.5 (e)0.5 (u)0.5 (r)0.5 (o)0.6 (p)0.5 (a)-9.5 (t)0.5 (h)0.5 (y)0.5 ( \()0.5 (e)0.5 (.)0.5 (g)0.5 (.)0.6 (,)37.4 ( b)0.5 (o)0.5 (r)0.5 (t)0.5 (e)0.5 (z)0.5 (o)0.5 (m)0.5 (i)0.5 (b)0.5 (,)37.5 ( a)0.5 (m)0.5 (i)0.5 (o)0.5 (d)0.5 (a)0.5 (r)0.5 (o)0.5 (n)0.5 (e)0.5 (,)32 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.044 Td [(cispla)-9.8 (tin,)37.2 ( docetaxel,)37.2 ( pac)20.1 (litaxel,)37.2 ( vincristine,)37.2 ( disul\036ram,)37.2 ( phen)-9.8 (ytoin,)37.2 ( metronidazole,)37.1 ( alcohol\))-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td (can cause an additive effect and should be used with caution.)Tj /T1_0 1 Tf 0.017 Tw 0 -1.738 Td (7.4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Hormonal Contraceptives)Tj /T1_1 1 Tf 0.007 Tc 0.168 Tw -3.375 -1.584 Td [(Hormonal contraceptives increase the risk of thromboembolism.)37.2 ( It is not kno)-9.7 (wn)7 ( )]TJ 0.001 Tc 0.136 Tw 0 -1.044 Td [(wh)0.5 (e)0.5 (the)0.5 (r)0.5 ( c)0.5 (on)0.5 (com)0.5 (i)0.5 (ta)0.5 (nt)0.5 ( u)0.5 (se)0.5 ( of)0.5 ( h)0.5 (o)0.5 (rm)0.5 (on)0.5 (al)0.5 ( c)0.5 (on)0.5 (tr)0.5 (ac)0.5 (ep)0.5 (ti)0.5 (ve)0.5 (s fu)0.5 (rt)0.5 (he)0.5 (r in)0.5 (cr)0.5 (ea)0.5 (se)0.5 (s th)0.5 (e ri)0.5 (sk)0.5 ( o)0.5 (f)1 ( )]TJ -0.017 Tc 0.011 Tw 0 -1.044 Td [(thromboembolism )-36.8 (with THALOMID.)]TJ -0.019 Tc 0.036 Tw 0 -1.719 Td [(In 10 healthy women,)37 ( the pharmacokinetic pro\036les of norethindrone and ethin)-9.9 (yl estradiol)-19 ( )]TJ -0.008 Tc 0.093 Tw 0 -1.044 Td [(follo)-9.8 (wing administra)-9.8 (tion of a single dose containing 1.0 mg of norethindrone aceta)-9.8 (te)-8 ( )]TJ -0.017 Tc 0.058 Tw 0 -1.044 Td [(and 75 mcg of ethin)-9.8 (yl estradiol were studied.)37.2 ( )37.3 (The results were similar with and without)-17 ( )]TJ 0.048 Tw 0 -1.044 Td [(coadministra)-9.8 (tion of )37.2 (THALOMID 200 mg/day to stead)-9.8 (y-sta)-9.7 (te levels.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.828 Td (7.5)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(W)18.2 (arf)20.2 (arin)]TJ /T1_1 1 Tf -0.013 Tc 0.068 Tw -3.375 -1.584 Td [(In 13 healthy men,)37.2 ( the pharmacokinetic pro\036le and interna)-9.8 (tional normalized ra)-9.8 (tio \(INR\))-13 ( )]TJ -0.009 Tc 0.092 Tw 0 -1.044 Td [(of )0.5 (prothrombin )0.5 (time )0.5 (for )0.5 (warfarin,)36.6 ( )0.5 (follo)-10.3 (wing )0.5 (a )0.5 (single )0.5 (oral )0.5 (dose )0.6 (of )0.5 (25 )0.5 (mg,)36.5 ( )0.6 (were )0.6 (similar)-9 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.044 Td [(w)0.5 (i)0.5 (th)0.5 ( )0.5 (a)0.5 (n)0.5 (d )0.5 (w)0.5 (i)0.5 (t)0.5 (ho)0.5 (u)0.5 (t)0.5 ( )0.5 (t)0.5 (he)0.5 ( )0.5 (c)0.5 (o)0.5 (a)0.5 (d)0.5 (mi)0.5 (n)0.5 (i)0.5 (st)0.5 (r)0.5 (a)-9.5 (t)0.5 (i)0.5 (o)0.5 (n )0.5 (o)0.5 (f)0.5 ( )37.5 (TH)0.5 (A)0.5 (L)0.5 (O)0.5 (MI)0.5 (D)0.5 ( )0.5 (2)0.5 (00)0.5 ( )0.5 (m)0.5 (g)0.5 (/d)0.5 (a)0.5 (y)0.5 ( )0.5 (a)-9.5 (t)0.5 ( s)0.5 (t)0.5 (e)0.5 (a)0.5 (d)-9.5 (y-)0.5 (s)0.5 (t)0.5 (a)-9.5 (t)0.5 (e)0.5 ( l)0.5 (e)0.5 (v)0.5 (e)0.5 (ls)0.5 (.)22 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td (The single dose of warfarin had no effect on the pharmacokinetic pro\036\ le of thalidomide.)Tj /T1_0 1 Tf 0.017 Tw 0 -1.738 Td (7.6)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Drugs that Interfere with Hormonal Contraceptives)Tj /T1_1 1 Tf 0.017 Tc 0.217 Tw -3.375 -1.584 Td [(Concomitant use of HIV)18.4 (-protease inhibitors,)37.3 ( griseofulvin,)37.4 ( modafinil,)37.4 ( penicillins,)54 ( )]TJ -0.008 Tc 0.096 Tw 0 -1.044 Td [(rifampin,)36.7 ( )0.5 (rifabutin,)36.7 ( )0.5 (phen)-10.3 (ytoin,)36.8 ( )0.5 (carbamazepine,)36.8 ( )0.5 (or certain herbal )0.5 (supplements )0.5 (such as)-8 ( )]TJ -0.007 Tc 0.097 Tw 0 -1.044 Td [(St.)37.3 ( John\222)55.3 (s )36.8 (W)18.3 (ort with hormonal contraceptive a)-9.7 (gents may reduce the effectiveness of)-7 ( )]TJ -0.017 Tc 0.052 Tw 0 -1.044 Td [(the contraception up to one month after discontinua)-9.7 (tion of these concomitant thera)-9.8 (pies.)20 ( )]TJ -0.012 Tc 0.071 Tw 0 -1.044 Td [(T)0.5 (h)0.5 (e)0.5 (r)0.5 (e)0.5 (f)0.5 (o)0.6 (r)0.5 (e)0.5 (,)37.5 ( f)0.6 (em)0.6 (a)0.5 (l)0.5 (e)0.5 (s)0.5 ( r)0.5 (e)0.5 (q)0.5 (u)0.5 (i)0.5 (r)0.5 (i)0.5 (n)0.5 (g)0.5 ( t)0.5 (r)0.5 (e)0.5 (a)-9.5 (t)0.5 (m)0.5 (e)0.5 (n)0.5 (t)0.6 ( w)0.5 (i)0.5 (t)0.5 (h)0.5 ( o)0.5 (n)0.5 (e)0.5 ( o)0.5 (r)0.5 ( m)0.5 (o)0.5 (r)0.5 (e)0.5 ( o)0.5 (f)0.5 ( t)0.5 (h)0.5 (e)0.5 (s)0.5 (e)0.5 ( d)0.5 (r)0.5 (u)0.5 (g)0.5 (s)0.5 ( m)0.5 (u)0.6 (s)0.5 (t)0.5 ( u)0.5 (s)0.5 (e)0.5 ( t)0.5 (w)0.5 (o)-12 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(OTHER effective or highly effective methods of contraception while takin\ g )37.2 (THALOMID.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.738 Td (7.7)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Concomitant Therapies that may Increase the Risk of Thromboembolism)Tj /T1_1 1 Tf -0.013 Tc 0.07 Tw -3.375 -1.584 Td [(Er)-18.1 (ythropoietic a)-10.1 (gents,)36.9 ( or other a)-10.1 (gents tha)-10.1 (t may increase the risk of thromboembolism,)24 ( )]TJ 0.008 Tc 0.174 Tw 0 -1.044 Td [(such as estrogen containing thera)-9.9 (pies,)37 ( should be used with caution in multiple)8 ( )]TJ 0.01 Tc 0.186 Tw 0 -1.044 Td [(myeloma pa)-10.3 (tients receiving )37.3 (THALOMID with dexamethasone )]TJ /T1_2 1 Tf 0.149 Tw [([see W)17.8 (arnings )-36.6 (and)9.9 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.044 Td (Precautio)Tj 0.048 Tw (ns \(5.3\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -2.003 Td (8)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(USE IN SPECIFIC POPULA)55.2 (TIONS)-17 ( )]TJ 0.017 Tw -3.375 -1.648 Td (8.1)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(Pregnanc)10.2 (y)]TJ /T1_1 1 Tf 0.048 Tw -3.375 -1.536 Td [(Pregnanc)20.2 (y Exposure Registr)-17.8 (y)]TJ -0.011 Tc 0.079 Tw 0 -1.539 Td [(There )0.5 (is )0.6 (a )0.5 (pregnanc)20.1 (y )0.5 (exposure )0.5 (registr)-17.9 (y )0.6 (tha)-9.8 (t )0.5 (monitors )0.5 (pregnanc)20.1 (y )0.5 (outcomes )0.6 (in )0.5 (females)-11 ( )]TJ -0.008 Tc 0.092 Tw 0 -1.044 Td [(exposed to )36.6 (THALOMID during pregnanc)20.2 (y as well as female partners of male pa)-9.7 (tients)-8 ( )]TJ -0.014 Tc 0.061 Tw 0 -1.044 Td [(w)0.5 (h)0.5 (o)0.5 ( a)0.5 (r)0.5 (e)0.5 ( e)0.5 (x)0.5 (p)0.6 (o)0.5 (s)0.5 (e)0.5 (d)0.5 ( t)0.5 (o)0.5 ( )37.1 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.5 (I)0.5 (D)0.5 (.)37.5 ( )37 (T)0.5 (h)0.5 (i)0.5 (s)0.5 ( r)0.6 (e)0.5 (g)0.5 (i)0.5 (s)0.5 (t)0.5 (r)-17.5 (y)0.5 ( i)0.6 (s)0.5 ( a)0.5 (l)0.5 (s)0.5 (o)0.5 ( u)0.5 (s)0.5 (e)0.5 (d)0.5 ( t)0.5 (o)0.5 ( u)0.5 (n)0.5 (d)0.5 (e)0.5 (r)0.5 (s)0.5 (t)0.5 (a)0.5 (n)0.5 (d)0.5 ( t)0.5 (h)0.5 (e)0.5 ( r)0.5 (o)0.6 (o)0.5 (t)0.5 ( c)0.5 (a)0.5 (u)0.5 (s)0.5 (e)-14 ( )]TJ -0.017 Tc 0.05 Tw 0 -1.044 Td [(for the pregnanc)20.2 (y)55.2 (.)37.2 ( Report an)-9.8 (y suspected fetal exposure to )36.9 (THALOMID to the FDA via the)-17 ( )]TJ -0.022 Tc 0.036 Tw 0 -1.044 Td [(MedW)17.9 (a)-10.1 (tch program a)-10.1 (t 1-800-FDA-1088 and to Celgene Corpora)-10.1 (tion a)-10.1 (t 1-888-423-5436.)]TJ -0.017 Tc 0.048 Tw 0 -1.671 Td [(Risk Summar)-17.8 (y)]TJ -0.002 Tc 0.126 Tw 0 -1.539 Td (Based on the mechanism of action )Tj /T1_2 1 Tf [([see Clinical Pharmacolog)-10.3 (y \(12.1\)])]TJ /T1_1 1 Tf [(,)36.7 ( human and)-2 ( )]TJ -0.008 Tc 0.095 Tw -0 -1.044 Td [(animal da)-10.2 (ta )]TJ /T1_2 1 Tf [(\(see Da)-10.2 (ta\))]TJ /T1_1 1 Tf [(,)36.7 ( )36.7 (THALOMID can cause embr)-18.2 (yo-fetal harm when administered)-8.1 ( )]TJ -0.004 Tc 0.116 Tw 0 -1.044 Td [(to a pregnant female and is contraindica)-10.2 (ted during pregnanc)19.7 (y )]TJ /T1_2 1 Tf 0.079 Tw [([see )-36.7 (Boxed W)17.7 (arning,)33 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(Contraindica)-9.8 (tions \(4.1\),)37.2 ( and )37.3 (W)18.2 (arnings and Precautio)]TJ (ns \(5.1\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj 0.022 Tc 0.245 Tw 0 -1.719 Td [(THALOMID )0.5 (is a human )0.5 (tera)-10 (togen,)36.9 ( inducing )0.5 (a )0.5 (high frequenc)19.9 (y )0.5 (of severe and)22 ( )]TJ -0.002 Tc 0.126 Tw 0 -1.044 Td [(life-threa)-10.3 (tening birth defects such as amelia \(absence of limbs\),)36.6 ( phocomelia \(short)-1.9 ( )]TJ 0.005 Tc 0.157 Tw 0 -1.044 Td [(limbs\),)37.3 ( hypoplasticity of the bones,)37.3 ( absence of bones,)37.3 ( external ear abnormalities)5 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.044 Td [(\(inc)19.7 (luding anotia,)36.7 ( micropinna,)36.7 ( small or absent external auditor)-18.3 (y canals\),)36.7 ( facial palsy)54.7 (,)36.7 ( eye)-17 ( )]TJ 0.042 Tw 0 -1.044 Td [(abnormalities \(anophthalmos,)37.2 ( microphthalmos\),)37.2 ( and congenital heart defects.)37.2 ( )36.7 (Alimentar)-17.8 (y)-17 ( )]TJ 0.047 Tw 0 -1.044 Td [(tract,)37.2 ( urinar)-17.8 (y tract,)37.2 ( and genital malforma)-9.7 (tions ha)-9.8 (ve also been documented and mortality)-17 ( )]TJ 0 Tc 0.137 Tw 0 -1.044 Td [(a)-10.4 (t )0.5 (or )0.5 (shortly )0.5 (after birth has )0.5 (been )0.5 (reported )0.5 (in )0.5 (about 40% )0.5 (of infants.)36.6 ( )0.5 (Even )0.5 (a )0.5 (single )]TJ -0.01 Tc 0.084 Tw 0 -1.044 Td [(dose taken by a pregnant woman can cause birth defects.)37.1 ( If this drug is used during)-9.9 ( )]TJ -0.017 Tc 0.054 Tw 0 -1.044 Td [(pregnanc)20.2 (y)55.2 (,)37.2 ( or if the pa)-9.8 (tient becomes pregnant while taking this drug,)37.3 ( the pa)-9.8 (tient should)-17 ( )]TJ 0.048 Tw 0 -1.044 Td [(be a)-9.7 (pprised of the potential risk to a fetus.)]TJ ET endstream endobj 84 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q 0.5 w /GS1 gs q 1 0 0 1 172.08 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 212.4 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 252.72 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 36 618.8223 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 618.8223 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 618.8223 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 608.0704 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 608.0704 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 608.0704 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 597.3185 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 597.3185 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 597.3185 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 586.5665 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 586.5665 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 586.5665 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 575.8146 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 575.8146 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 575.8146 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 500.5513 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 500.5513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 500.5513 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 565.0627 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 565.0627 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 565.0627 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 554.3108 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 554.3108 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 554.3108 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 543.5589 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 543.5589 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 543.5589 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 532.807 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 532.807 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 532.807 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 522.0551 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 522.0551 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 522.0551 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 511.3032 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 511.3032 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 511.3032 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 489.7993 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 489.7993 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 489.7993 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 479.0474 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 479.0474 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 479.0474 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 468.2955 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 468.2955 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 468.2955 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 457.5436 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 457.5436 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 457.5436 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 446.7917 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 446.7917 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 446.7917 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 436.0398 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 436.0398 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 436.0398 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 425.2878 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 425.2878 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 425.2878 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 382.2802 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 382.2802 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 382.2802 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 300.7687 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 300.7687 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 300.7687 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 268.513 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 268.513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 268.513 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 257.761 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 257.761 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 257.761 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 214.7534 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 214.7534 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 214.7534 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 150.2419 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 150.2419 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 150.2419 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 414.5359 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 414.5359 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 414.5359 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 403.784 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 403.784 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 403.784 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 393.0321 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 393.0321 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 393.0321 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 371.5283 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 371.5283 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 371.5283 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 352.2764 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 352.2764 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 352.2764 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 341.5244 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 341.5244 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 341.5244 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 330.7726 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 330.7726 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 330.7726 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 320.0206 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 320.0206 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 320.0206 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 290.0168 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 290.0168 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 290.0168 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 279.2649 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 279.2649 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 279.2649 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 247.0092 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 247.0092 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 247.0092 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 236.2572 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 236.2572 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 236.2572 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 225.5053 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 225.5053 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 225.5053 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 204.0015 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 204.0015 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 204.0015 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 193.2496 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 193.2496 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 193.2496 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 182.4977 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 182.4977 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 182.4977 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 171.7457 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 171.7457 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 171.7457 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 160.9938 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 160.9938 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 160.9938 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 139.49 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 139.49 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 139.49 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 128.7381 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 172.08 128.7381 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 128.7381 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 131.76 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 172.08 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 629.8242 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 131.76 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 172.08 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 131.76 618.8223 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 608.0704 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 597.3185 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 586.5665 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 576.0646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 576.0646 cm 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10.252 l S Q q 1 0 0 1 172.08 500.8013 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 500.5513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 490.0493 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 490.0493 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 489.7993 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 479.2974 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 479.2974 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 479.0474 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 468.5455 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 468.5455 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 468.2955 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 457.7936 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 457.7936 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 457.5436 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 447.0417 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 447.0417 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 446.7917 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 436.2898 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 436.2898 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 436.0398 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 425.5378 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 425.5378 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 425.2878 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 414.7859 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 414.7859 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 414.5359 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 404.034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 404.034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 403.784 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 393.2821 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 393.2821 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 393.0321 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 382.5302 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 382.5302 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 382.2802 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 371.7783 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 371.7783 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 371.5283 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 352.5264 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 172.08 352.5264 cm 0 0 m 0 18.752 l S Q q 1 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172.08 268.763 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 268.513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 258.011 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 258.011 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 257.761 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 247.2592 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 247.2592 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 247.0092 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 236.5072 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 236.5072 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 236.2572 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 225.7553 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 225.7553 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 225.5053 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 215.0034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 215.0034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 214.7534 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 204.2515 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 204.2515 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 204.0015 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 193.4996 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 193.4996 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 193.2496 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 182.7477 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 182.7477 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 182.4977 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 171.9957 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 171.9957 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 171.7457 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 161.2438 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 161.2438 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 160.9938 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 150.4919 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 150.4919 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 150.2419 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 139.74 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 139.74 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 139.49 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 131.76 128.9881 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 172.08 128.9881 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 131.76 128.7381 cm 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10.252 l S Q q 1 0 0 1 212.4 414.5359 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 404.034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 404.034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 403.784 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 393.2821 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 393.2821 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 393.0321 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 382.5302 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 382.5302 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 382.2802 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 371.7783 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 371.7783 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 371.5283 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 352.5264 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 252.72 352.5264 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 212.4 352.2764 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 341.7744 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 341.7744 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 341.5244 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 331.0226 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 331.0226 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 330.7726 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 320.2706 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 320.2706 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 320.0206 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 301.0187 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 252.72 301.0187 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 212.4 300.7687 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 290.2668 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 290.2668 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 290.0168 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 279.5149 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 279.5149 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 279.2649 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 268.763 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 268.763 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 268.513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 258.011 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 258.011 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 257.761 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 247.2592 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 247.2592 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 247.0092 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 236.5072 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 236.5072 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 236.2572 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 225.7553 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 225.7553 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 225.5053 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 215.0034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 215.0034 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 214.7534 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 204.2515 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 204.2515 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 204.0015 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 193.4996 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 193.4996 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 193.2496 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 182.7477 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 182.7477 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 182.4977 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 171.9957 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 171.9957 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 171.7457 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 161.2438 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 161.2438 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 160.9938 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 150.4919 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 150.4919 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 150.2419 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 139.74 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 139.74 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 139.49 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 128.9881 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 128.9881 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 212.4 128.7381 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 118.2361 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 252.72 118.2361 cm 0 0 m 0 10.252 l S Q 1 w q 1 0 0 1 36 715.1481 cm 0 0 m 95.76 0 l S Q 0.5 w q 1 0 0 1 131.76 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 36 629.8242 cm 0 0 m 95.76 0 l S Q 1 w q 1 0 0 1 131.76 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 172.08 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 715.1481 cm 0 0 m 35.28 0 l S Q 0.5 w q 1 0 0 1 131.76 676.9861 cm 0 0 m 0 37.662 l S Q q 1 0 0 1 172.08 676.9861 cm 0 0 m 0 37.662 l S Q q 1 0 0 1 131.51 676.7361 cm 0 0 m 40.57 0 l S Q q 1 0 0 1 172.08 676.7361 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 676.7361 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 676.7361 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 36 117.9861 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 131.76 117.9861 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 172.08 117.9861 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 212.4 117.9861 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 252.72 117.9861 cm 0 0 m 35.28 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.021 Tc 0.036 Tw 8 0 0 8 36 727.248 Tm [(T)70.2 (a)-3.8 (b)-3.8 (l)-3.8 (e)-3.8 ( )-15.8 (4)-3.7 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Summar)-18.3 (y of Adverse Reactions \(ARs\) Reported in Celgene-sponsored)-21 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(Controlled Clinical T)74.2 (rials)]TJ -0.012 Tc 7.6 0 0 8 36 673.8802 Tm (Body System/)Tj 0 Tc 0 Tw 7.6 0 0 8 76.9617 673.8802 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 36 665.3802 Tm (Adverse Reaction)Tj 13.849 5.057 Td [(All ARs)-12 ( )]TJ 0.012 Tw -0.349 -1.062 Td (Reported)Tj 0.048 Tw -0.308 -1.062 Td [(in P)24.2 (atients)-11.9 ( )]TJ 0.33 -1.062 Td (with ENL)Tj 4.974 1.062 Td [(ARs Reported in \0363 HIV)18.2 (-seropositive)-12 ( )]TJ 0.012 Tw 5.487 -1.062 Td [(P)24.2 (atients)]TJ -10.779 -1.614 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 167.4908 667.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 144.4144 658.9242 Tm [(50 to)-12 ( )]TJ 0 Tc 0 Tw 7.6 0 0 8 161.4289 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 134.3141 650.4242 Tm (300 mg/day)Tj 0 Tc 0 Tw 7.6 0 0 8 169.5259 650.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 140.7452 641.9242 Tm ( \(N=24\))Tj 0 Tc 0 Tw 7.6 0 0 8 163.0948 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 143.9052 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.311 3.188 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 207.8108 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 174.6341 650.4242 Tm [(100 mg/day)-12 ( )]TJ 0.012 Tw 0.984 -1.062 Td (\(N=36\))Tj 0 Tc 0 Tw 7.6 0 0 8 202.3668 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 184.2252 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.311 3.188 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 248.1308 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 214.9541 650.4242 Tm [(200 mg/day)-12 ( )]TJ 0.012 Tw 0.984 -1.062 Td (\(N=32\))Tj 0 Tc 0 Tw 7.6 0 0 8 242.6868 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 224.5452 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.508 2.125 Td (Placebo)Tj 0 Tc 0 Tw 7.6 0 0 8 282.1615 650.4242 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 260.3582 641.9242 Tm (\(N=35\))Tj 0 Tc 0 Tw 7.6 0 0 8 280.6118 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 262.4702 633.4242 Tm (n \(%\))Tj -29.799 -1.51 Td [(Blood and L)37.2 (ymphatic)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.416 0 Td (8 \(22\))Tj 5.071 0 Td (13 \(41\))Tj 4.99 0 Td (10 \(29\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.49 -1.344 Td ( )Tj EMC (Anemia)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (2 \(6\))Tj 5.071 0 Td (4 \(13\))Tj 5.224 0 Td (3 \(9\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Leukopenia)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (6 \(17\))Tj 5.305 0 Td (8 \(25\))Tj 5.224 0 Td (3 \(9\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(L)37.2 (ymphadenopa)-9.8 (thy)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (2 \(6\))Tj 5.071 0 Td (4 \(13\))Tj 5.224 0 Td (3 \(9\))Tj /T1_0 1 Tf -30.013 -1.344 Td (Body as a Whole)Tj 13.889 0 Td (16 \(67\))Tj 5.305 0 Td (18 \(50\))Tj 5.305 0 Td (19 \(59\))Tj 4.99 0 Td (13 \(37\))Tj /T1_1 1 Tf /Span<>> BDC -29.49 -1.344 Td ( )Tj EMC 0.592 0 Td (Abdominal pain)Tj 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (1 \(3\))Tj 5.305 0 Td (1 \(3\))Tj 4.756 0 Td (4 \(11\))Tj /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC 0.592 0 Td [(Accidental injur)-17.8 (y)]TJ 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (2 \(6\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.39 0 Td (1 \(3\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Asthenia)Tj 0.048 Tw 14.412 0 Td (2 \(8\))Tj 5.305 0 Td (2 \(6\))Tj 5.071 0 Td (7 \(22\))Tj 5.224 0 Td (1 \(3\))Tj /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC 0.592 0 Td (Back pain)Tj 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (2 \(6\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Chills)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(9\))Tj 4.756 0 Td (4 \(11\))Tj /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC 0.592 0 Td [(F)20.2 (acial edema)]TJ 13.82 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC [(F)24.2 (ever)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (7 \(19\))Tj 5.305 0 Td (7 \(22\))Tj 4.99 0 Td (6 \(17\))Tj 0.364 Tw /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC (Headache)Tj 0.048 Tw 14.178 0 Td (3 \(13\))Tj 5.305 0 Td (6 \(17\))Tj 5.305 0 Td (6 \(19\))Tj 4.99 0 Td (4 \(11\))Tj 0.364 Tw /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC (Infection)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(8\))Tj 5.305 0 Td (2 \(6\))Tj 4.99 0 Td (1 \(3\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Malaise)Tj 0.048 Tw 14.412 0 Td (2 \(8\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.048 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC 0.592 0 Td (Neck pain)Tj 13.82 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.048 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC 0.592 0 Td (Neck rigidity)Tj 13.82 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC [(P)18.2 (ain)]TJ 0.048 Tw 14.412 0 Td (2 \(8\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (1 \(3\))Tj 4.99 0 Td (2 \(6\))Tj /T1_0 1 Tf -30.013 -1.344 Td (Digestive System)Tj 14.123 0 Td (5 \(21\))Tj 5.071 0 Td (16 \(44\))Tj 5.305 0 Td (16 \(50\))Tj 4.99 0 Td (15 \(43\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.49 -1.344 Td ( )Tj EMC (Anorexia)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (1 \(3\))Tj 5.305 0 Td (3 \(9\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(Constipa)-9.8 (tion)]TJ 0.048 Tw 14.412 0 Td (1 \(4\))Tj 5.305 0 Td (1 \(3\))Tj 5.305 0 Td (3 \(9\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Diarrhea)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 5.071 0 Td (4 \(11\))Tj 5.305 0 Td (6 \(19\))Tj 4.99 0 Td (6 \(17\))Tj /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC 0.592 0 Td [(Dr)-17.8 (y mouth)]TJ 0 Tc 0 Tw 14.421 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(8\))Tj 5.305 0 Td (3 \(9\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(Fla)-9.7 (tulence)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(8\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.39 0 Td (2 \(6\))Tj /Span<>> BDC -30.013 -1.344 Td [( )-316.1 ( )]TJ EMC 0.592 0 Td [(Liver function tests multiple)-12 ( )]TJ 0.012 Tw 0 -1.062 Td (abnormalities)Tj 0 Tc 0 Tw 14.421 0.531 Td (0)Tj 5.305 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(9\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.875 Td ( )Tj EMC (Nausea)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (4 \(13\))Tj 5.224 0 Td (1 \(3\))Tj /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC 0.592 0 Td (Oral moniliasis)Tj 13.82 0 Td (1 \(4\))Tj 5.071 0 Td (4 \(11\))Tj 5.539 0 Td (2 \(6\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.048 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC 0.592 0 Td [(T)74.2 (ooth pain)]TJ 13.82 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj /T1_0 1 Tf -0.012 Tc 0.048 Tw -30.613 -1.344 Td [(Metabolic and Endocrine)-12 ( )]TJ 0.012 Tw 0 -1.062 Td (Disorders)Tj 0.048 Tw 14.357 0.531 Td (1 \(4\))Tj 5.071 0 Td (8 \(22\))Tj 5.071 0 Td (12 \(38\))Tj 5.224 0 Td (8 \(23\))Tj /T1_1 1 Tf /Span<>> BDC -29.724 -1.875 Td ( )Tj EMC 0.592 0 Td (Edema peripheral)Tj 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (3 \(8\))Tj 5.305 0 Td (1 \(3\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Hyperlipidemia)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (2 \(6\))Tj 5.305 0 Td (3 \(9\))Tj 4.99 0 Td (1 \(3\))Tj /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC 0.592 0 Td (SGOT increased)Tj 0 Tc 0 Tw 14.421 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (1 \(3\))Tj 5.071 0 Td (4 \(13\))Tj 5.224 0 Td (2 \(6\))Tj /T1_0 1 Tf -30.013 -1.344 Td [(Ner)-17.7 (vous System)]TJ 13.889 0 Td (13 \(54\))Tj 5.305 0 Td (19 \(53\))Tj 5.305 0 Td (18 \(56\))Tj 4.99 0 Td (12 \(34\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.49 -1.344 Td ( )Tj EMC [(Agita)-9.7 (tion)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj 5.305 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(9\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Dizziness)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 5.071 0 Td (7 \(19\))Tj 5.305 0 Td (6 \(19\))Tj 0 Tc 0 Tw 5.825 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Insomnia)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj 5.305 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(9\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(Ner)-17.7 (vousness)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (1 \(3\))Tj 5.305 0 Td (3 \(9\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC [(Neuropa)-9.8 (thy)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(8\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC [(P)18.2 (aresthesia)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (2 \(6\))Tj 5.071 0 Td (5 \(16\))Tj 4.99 0 Td (4 \(11\))Tj 0.364 Tw /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC (Somnolence)Tj 0.048 Tw 14.178 0 Td (9 \(38\))Tj 5.071 0 Td (13 \(36\))Tj 5.305 0 Td (12 \(38\))Tj 5.224 0 Td (4 \(11\))Tj 0.364 Tw /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC [(T)74.2 (remor)]TJ 0.048 Tw 14.412 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC [(V)18.2 (ertigo)]TJ 0.048 Tw 14.412 0 Td (2 \(8\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj 4.99 0 Td (0)Tj /T1_0 1 Tf -0.012 Tc 0.048 Tw -30.613 -1.344 Td [(Respirator)-17.7 (y System)]TJ 14.123 0 Td (3 \(13\))Tj 5.305 0 Td (9 \(25\))Tj 5.305 0 Td (6 \(19\))Tj 4.99 0 Td (9 \(26\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.724 -1.344 Td ( )Tj EMC [(Phar)-17.7 (yngitis)]TJ 0.048 Tw 14.412 0 Td (1 \(4\))Tj 5.305 0 Td (3 \(8\))Tj 5.305 0 Td (2 \(6\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Rhinitis)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 5.305 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.156 0 Td (4 \(11\))Tj 0.364 Tw /Span<>> BDC -29.779 -1.344 Td ( )Tj EMC (Sinusitis)Tj 0.048 Tw 14.412 0 Td (1 \(4\))Tj 5.305 0 Td (3 \(8\))Tj 5.305 0 Td (1 \(3\))Tj 4.99 0 Td (2 \(6\))Tj /T1_2 1 Tf 0 Tc 0 Tw 8 0 0 8 255.7445 109.512 Tm (\()Tj -0.017 Tc 0.017 Tw 0.224 0 Td (Continued\))Tj ET /GS1 gs q 1 0 0 1 460.08 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 500.4 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 540.72 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 324 618.8223 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 618.8223 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 618.8223 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 597.3185 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 597.3185 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 597.3185 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 575.8146 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 575.8146 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 575.8146 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 532.807 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 532.807 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 532.807 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 522.0551 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 522.0551 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 522.0551 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 608.0704 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 608.0704 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 608.0704 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 586.5665 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 586.5665 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 586.5665 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 565.0627 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 565.0627 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 565.0627 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 554.3108 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 554.3108 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 554.3108 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 543.5589 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 543.5589 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 543.5589 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 511.3032 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 460.08 511.3032 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 511.3032 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 419.76 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 460.08 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 629.8242 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 629.8242 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 419.76 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 460.08 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 419.76 618.8223 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 608.0704 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 597.3185 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 586.5665 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 576.0646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 576.0646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 575.8146 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 565.3127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 565.3127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 565.0627 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 554.5608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 554.5608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 554.3108 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 543.8089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 543.8089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 543.5589 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 533.057 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 533.057 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 532.807 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 522.3051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 522.3051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 522.0551 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 511.5532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 460.08 511.5532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 419.76 511.3032 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 419.76 501.0513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 460.08 501.0513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 500.4 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 540.72 619.0723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 500.4 618.8223 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 608.3204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 608.0704 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 597.5685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 597.3185 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 586.8165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 586.5665 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 576.0646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 576.0646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 575.8146 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 565.3127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 565.3127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 565.0627 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 554.5608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 554.5608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 554.3108 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 543.8089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 543.8089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 543.5589 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 533.057 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 533.057 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 532.807 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 522.3051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 522.3051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 522.0551 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 511.5532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 540.72 511.5532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 500.4 511.3032 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 501.0513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 540.72 501.0513 cm 0 0 m 0 10.002 l S Q 1 w q 1 0 0 1 324 500.5513 cm 0 0 m 95.76 0 l S Q q 1 0 0 1 419.76 500.5513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 460.08 500.5513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 500.5513 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 500.5513 cm 0 0 m 35.28 0 l S Q q 1 0 0 1 324 715.1481 cm 0 0 m 95.76 0 l S Q 0.5 w q 1 0 0 1 419.76 630.0742 cm 0 0 m 0 46.412 l S Q q 1 0 0 1 324 629.8242 cm 0 0 m 95.76 0 l S Q 1 w q 1 0 0 1 419.76 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 460.08 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 715.1481 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 715.1481 cm 0 0 m 35.28 0 l S Q 0.5 w q 1 0 0 1 419.76 676.9861 cm 0 0 m 0 37.662 l S Q q 1 0 0 1 460.08 676.9861 cm 0 0 m 0 37.662 l S Q q 1 0 0 1 419.51 676.7361 cm 0 0 m 40.57 0 l S Q q 1 0 0 1 460.08 676.7361 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 500.4 676.7361 cm 0 0 m 40.32 0 l S Q q 1 0 0 1 540.72 676.7361 cm 0 0 m 35.28 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.021 Tc 0.036 Tw 8 0 0 8 324 727.248 Tm [(T)70.2 (a)-3.8 (b)-3.8 (l)-3.8 (e)-3.8 ( )-15.8 (4)-3.7 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Summar)-18.3 (y of Adverse Reactions \(ARs\) Reported in Celgene-sponsored)-21 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(Controlled Clinical T)74.2 (rials)]TJ -0.012 Tc 7.6 0 0 8 324 673.8802 Tm (Body System/)Tj 0 Tc 0 Tw 7.6 0 0 8 364.9617 673.8802 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 324 665.3802 Tm (Adverse Reaction)Tj 13.849 5.057 Td [(All ARs)-12 ( )]TJ 0.012 Tw -0.349 -1.062 Td (Reported)Tj 0.048 Tw -0.308 -1.062 Td [(in P)24.2 (atients)-12 ( )]TJ 0.33 -1.062 Td (with ENL)Tj 4.974 1.062 Td [(ARs Reported in \0363 HIV)18.2 (-seropositive)-12 ( )]TJ 0.012 Tw 5.487 -1.062 Td [(P)24.2 (atients)]TJ -10.779 -1.614 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 455.4907 667.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 432.4143 658.9242 Tm [(50 to)-12 ( )]TJ 0 Tc 0 Tw 7.6 0 0 8 449.4288 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 422.3141 650.4242 Tm (300 mg/day)Tj 0 Tc 0 Tw 7.6 0 0 8 457.5258 650.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 428.7451 641.9242 Tm ( \(N=24\))Tj 0 Tc 0 Tw 7.6 0 0 8 451.0947 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 431.9051 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.311 3.188 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 495.8107 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 462.6341 650.4242 Tm [(100 mg/day)-12 ( )]TJ 0.012 Tw 0.984 -1.062 Td (\(N=36\))Tj 0 Tc 0 Tw 7.6 0 0 8 490.3668 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 472.2251 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.311 3.188 Td (THALOMID)Tj 0 Tc 0 Tw 7.6 0 0 8 536.1307 658.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 502.954 650.4242 Tm [(200 mg/day)-12 ( )]TJ 0.012 Tw 0.984 -1.062 Td (\(N=32\))Tj 0 Tc 0 Tw 7.6 0 0 8 530.6868 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 512.5451 633.4242 Tm (n \(%\))Tj 0.012 Tw 4.508 2.125 Td (Placebo)Tj 0 Tc 0 Tw 7.6 0 0 8 570.1615 650.4242 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 548.3582 641.9242 Tm (\(N=35\))Tj 0 Tc 0 Tw 7.6 0 0 8 568.6118 641.9242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 550.4702 633.4242 Tm (n \(%\))Tj -29.799 -1.51 Td (Skin and Appendages)Tj 13.889 0 Td (10 \(42\))Tj 5.305 0 Td (17 \(47\))Tj 5.305 0 Td (18 \(56\))Tj 4.99 0 Td (19 \(54\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.49 -1.344 Td ( )Tj EMC (Acne)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (4 \(11\))Tj 5.539 0 Td (1 \(3\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.048 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC 0.592 0 Td [(Derma)-9.8 (titis fungal)]TJ 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (2 \(6\))Tj 5.305 0 Td (3 \(9\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.048 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC 0.592 0 Td (Nail disorder)Tj 13.82 0 Td (1 \(4\))Tj 5.305 0 Td (0 \(0\))Tj 5.305 0 Td (1 \(3\))Tj 0 Tc 0 Tw 5.591 0 Td (0)Tj -0.012 Tc 0.364 Tw /Span<>> BDC -30.613 -1.344 Td ( )Tj EMC (Pruritus)Tj 0.048 Tw 14.412 0 Td (2 \(8\))Tj 5.305 0 Td (1 \(3\))Tj 5.305 0 Td (2 \(6\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Rash)Tj 0.048 Tw 14.178 0 Td (5 \(21\))Tj 5.305 0 Td (9 \(25\))Tj 5.305 0 Td (8 \(25\))Tj 4.756 0 Td (11 \(31\))Tj /Span<>> BDC -29.545 -1.344 Td ( )Tj EMC 0.592 0 Td [(Rash maculopa)-9.8 (pular)]TJ 13.82 0 Td (1 \(4\))Tj 5.071 0 Td (6 \(17\))Tj 5.305 0 Td (6 \(19\))Tj 5.224 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(Swea)-9.7 (ting)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj 5.305 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (4 \(13\))Tj 4.99 0 Td (4 \(11\))Tj /T1_0 1 Tf -29.779 -1.344 Td (Urogenital System)Tj 14.357 0 Td (2 \(8\))Tj 5.071 0 Td (6 \(17\))Tj 5.539 0 Td (2 \(6\))Tj 4.756 0 Td (4 \(11\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -29.724 -1.344 Td ( )Tj EMC (Albuminuria)Tj 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.705 0 Td (3 \(8\))Tj 5.305 0 Td (1 \(3\))Tj 4.99 0 Td (2 \(6\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC [(Hema)-9.8 (turia)]TJ 0 Tc 0 Tw 15.013 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.471 0 Td (4 \(11\))Tj 0 Tc 0 Tw 6.14 0 Td (0)Tj -0.012 Tc 0.048 Tw 4.39 0 Td (1 \(3\))Tj 0.364 Tw /Span<>> BDC -30.013 -1.344 Td ( )Tj EMC (Impotence)Tj 0.048 Tw 14.412 0 Td (2 \(8\))Tj 5.305 0 Td (1 \(3\))Tj 0 Tc 0 Tw 5.906 0 Td (0)Tj 4.99 0 Td (0)Tj /T1_0 1 Tf -0.017 Tc 0.048 Tw 8 0 0 8 324 483.8051 Tm [(Other Adverse Reactions Obser)-17.8 (ved in ENL P)24.1 (atients)]TJ /T1_1 1 Tf -0.009 Tc 0.086 Tw 0 -1.545 Td [(T)0.5 (H)0.6 (A)0.5 (L)0.5 (O)0.6 (M)0.5 (I)0.5 (D)0.6 ( i)0.5 (n)0.5 ( d)0.6 (o)0.5 (s)0.5 (e)0.6 (s)0.5 ( u)0.5 (p)0.6 ( t)0.6 (o)0.5 ( 4)0.6 (0)0.5 (0)0.5 ( m)0.6 (g)0.5 (/)0.5 (d)0.5 (a)0.6 (y)0.5 ( h)0.6 (a)0.5 (s)0.5 ( b)0.6 (e)0.5 (e)0.6 (n)0.5 ( a)0.5 (d)0.5 (m)0.6 (i)0.5 (n)0.6 (i)0.5 (s)0.5 (t)0.6 (e)0.5 (r)0.5 (e)0.6 (d)0.5 ( i)0.5 (n)0.6 (v)0.5 (e)0.6 (s)0.5 (t)0.5 (i)0.5 (g)0.6 (a)-9.5 (t)0.6 (i)0.5 (o)0.6 (n)0.5 (a)0.5 (l)0.6 (l)0.5 (y)0.5 ( i)0.6 (n)0.5 ( t)0.5 (h)0.6 (e)-9 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.05 Td [(U)0.5 (n)0.5 (i)0.5 (t)0.6 (e)0.5 (d)0.5 ( )0.5 (S)0.6 (t)0.5 (a)-9.5 (t)0.6 (e)0.5 (s)0.5 ( )0.5 (o)0.6 (v)0.5 (e)0.5 (r)0.5 ( )0.6 (a)0.5 ( )0.5 (1)0.5 (9)0.6 (-)0.5 (y)0.5 (e)0.5 (a)0.6 (r)0.5 ( )0.5 (p)0.6 (e)0.5 (r)0.5 (i)0.5 (o)0.6 (d)0.5 ( )0.5 (i)0.5 (n)0.5 ( )0.6 (1)0.5 (4)0.5 (6)0.5 (5)0.5 ( )0.6 (p)0.5 (a)-9.5 (t)0.5 (i)0.6 (e)0.5 (n)0.5 (t)0.5 (s)0.6 ( )0.5 (w)0.5 (i)0.5 (t)0.6 (h)0.5 ( )0.5 (E)0.5 (N)0.5 (L)0.6 (.)37.5 ( )37.5 (T)0.5 (h)0.5 (e)0.5 ( )0.6 (p)0.5 (u)0.5 (b)0.5 (l)0.5 (i)0.6 (s)0.5 (h)0.5 (e)0.5 (d)0.6 ( )0.5 (l)0.5 (i)0.5 (t)0.6 (e)0.5 (r)0.5 (a)-9.5 (t)0.6 (u)0.5 (r)0.5 (e)-15 ( )]TJ -0.019 Tc 0.036 Tw 0 -1.05 Td [(de)0.5 (s)0.5 (cri)0.5 (be)0.5 (s )0.5 (th)0.5 (e )0.5 (tr)0.5 (e)0.5 (a)-9.6 (t)0.5 (me)0.5 (nt)0.5 ( o)0.5 (f )0.5 (an)0.5 ( a)0.5 (dd)0.5 (it)0.5 (io)0.5 (na)0.5 (l )0.5 (16)0.5 (78)0.5 ( p)0.5 (a)-9.6 (t)0.5 (ie)0.5 (nt)0.5 (s.)37.5 ( )37.4 (T)74.4 (o)0.5 ( p)0.5 (ro)0.5 (vi)0.5 (de)0.5 ( )0.5 (a )0.5 (me)0.5 (an)0.5 (in)0.5 (gf)0.5 (ul )0.5 (e)0.5 (st)0.5 (im)0.5 (a)-9.6 (t)0.5 (e)-19 ( )]TJ -0.021 Tc 0 -1.05 Td [(of the proportion of the individuals ha)-9.9 (ving adverse reactions,)37.1 ( similar types of events were)-21 ( )]TJ -0.01 Tc 0.081 Tw 0 -1.05 Td [(g)0.6 (r)0.5 (o)0.6 (u)0.5 (p)0.6 (e)0.5 (d)0.6 ( i)0.6 (n)0.5 (t)0.6 (o)0.5 ( a)0.5 ( s)0.5 (m)0.6 (a)0.6 (l)0.5 (l)0.6 (e)0.5 (r)0.6 ( n)0.6 (u)0.5 (m)0.6 (b)0.5 (e)0.6 (r)0.6 ( o)0.6 (f)0.5 ( s)0.5 (t)0.6 (a)0.5 (n)0.6 (d)0.5 (a)0.6 (r)0.6 (d)0.5 (i)0.6 (z)0.5 (e)0.6 (d)0.5 ( c)0.5 (a)-9.4 (t)0.5 (e)0.6 (g)0.6 (o)0.5 (r)0.6 (i)0.5 (e)0.6 (s)0.5 ( u)0.5 (s)0.6 (i)0.5 (n)0.6 (g)0.5 ( a)0.5 ( m)0.5 (o)0.6 (d)0.5 (i)0.6 (\036)0.5 (e)0.6 (d)0.6 ( C)0.6 (O)0.5 (S)0.5 (T)55.6 (A)0.5 (R)18.6 (T)-10 ( )]TJ -0.019 Tc 0.036 Tw 0 -1.05 Td [(d)0.5 (i)0.5 (ct)0.5 (i)0.5 (o)0.5 (na)0.5 (r)-17.5 (y)0.5 (/)0.5 (t)0.5 (e)0.5 (rm)0.5 (i)0.5 (n)0.5 (o)0.5 (lo)0.5 (g)-9.5 (y)55.5 (.)37.4 ( )37.5 (T)0.5 (h)0.5 (e)0.5 (se)0.5 ( )0.5 (c)0.5 (a)-9.5 (te)0.6 (go)0.5 (r)0.5 (i)0.5 (e)0.5 (s )0.5 (a)0.5 (r)0.5 (e)0.5 ( u)0.5 (s)0.5 (e)0.5 (d)0.5 ( i)0.5 (n)0.5 ( )0.5 (th)0.5 (e)0.5 ( )0.5 (l)0.5 (is)0.5 (t)0.5 (i)0.5 (n)0.5 (g )0.5 (b)0.5 (e)0.5 (l)0.5 (o)-9.6 (w)37.5 (.)37.5 ( )37.4 (A)0.5 (l)0.5 (l)0.5 ( )0.5 (re)0.5 (p)0.5 (o)0.5 (r)0.5 (t)0.5 (ed)0.5 ( )0.5 (e)0.5 (v)0.5 (en)0.5 (t)0.5 (s)-19 ( )]TJ -0.017 Tc 0.056 Tw 0 -1.05 Td [(are inc)20.2 (luded except those alread)-9.8 (y listed in the previous table.)37.2 ( Due to the fact tha)-9.8 (t these)-17 ( )]TJ 0.042 Tw 0 -1.05 Td [(da)-9.8 (ta were collected from uncontrolled studies,)37.2 ( the incidence ra)-9.8 (te cannot be determined.)20 ( )]TJ 0.004 Tc 0.152 Tw 0 -1.05 Td [(No )0.5 (caus)0.5 (al )0.5 (rela)-9.5 (tionshi)0.5 (p b)0.5 (etwee)0.5 (n )37.4 (TH)0.5 (ALOMID)0.5 ( an)0.5 (d t)0.5 (hese )0.5 (eve)0.5 (nts )0.5 (can )0.5 (be )0.5 (conc)20.5 (lusivel)0.5 (y)4 ( )]TJ -0.018 Tc 0.036 Tw 0 -1.05 Td [(determined a)-9.8 (t this time.)37.3 ( )37.2 (These are reports of all adverse events noted by investiga)-9.8 (tors in)-18 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(pa)-9.8 (tients to whom they had administered )37.2 (THALOMID.)]TJ /T1_0 1 Tf -0.001 Tc 0.131 Tw 0 -1.725 Td [(Blood and L)36.7 (ymphatic:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 9.144 0 Td [(ESR decrease,)36.6 ( eosinophilia,)36.7 ( granuloc)19.7 (ytopenia,)36.7 ( hypochromic)-1 ( )]TJ 0.003 Tc 0.151 Tw -9.144 -1.05 Td [(anemia,)36.7 ( leukemia,)36.7 ( leukoc)19.7 (ytosis,)36.8 ( leukopenia,)36.8 ( MCV eleva)-10.3 (ted,)36.8 ( RBC abnormal,)36.7 ( spleen)3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(palpable,)37.2 ( thromboc)20.2 (ytopenia.)]TJ /T1_0 1 Tf 0 -1.68 Td (Body as a Whole:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.937 0 Td [(Abdomen enlarged,)37.2 ( fever)74.2 (,)37.2 ( photosensitivity)55.2 (,)37.2 ( upper extremity pain.)]TJ /T1_0 1 Tf -0.008 Tc 0.093 Tw -6.937 -1.68 Td [(Cardio)-9.7 (v)16.2 (ascular System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC [(Brad)-9.7 (ycardia,)37.2 ( hypertension,)37.2 ( hypotension,)37.1 ( peripheral vascular)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(disorder)74.2 (,)37.2 ( tachycardia,)37.2 ( vasodila)-9.8 (tion.)]TJ /T1_0 1 Tf 0 Tc 0.137 Tw 0 -1.68 Td (Digestive System:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.508 0 Td [(Anorexia,)36.6 ( a)-10.4 (ppetite increase/weight gain,)36.5 ( dr)-18.4 (y mouth,)36.5 ( d)-10.4 (yspepsia,)37 ( )]TJ 0.02 Tc 0.234 Tw -7.508 -1.05 Td [(enlarged )0.5 (liver)74.1 (,)37.1 ( )0.5 (eructa)-9.9 (tion,)37.1 ( )0.5 (fla)-9.9 (tulence,)37.1 ( )0.5 (increased )0.5 (liver )0.5 (function )0.5 (tests,)37.1 ( )0.5 (intestinal)20 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(obstruction,)37.2 ( vomiting.)]TJ /T1_0 1 Tf 0.015 Tc 0.208 Tw 0 -1.68 Td (Metabolic and Endocrine:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 11.149 0 Td [(ADH ina)-9.9 (ppropria)-9.8 (te,)37.1 ( amyloidosis,)37.2 ( bilirubinemia,)37.1 ( BUN)15 ( )]TJ -0.007 Tc 0.099 Tw -11.149 -1.05 Td [(increased,)37 ( crea)-10 (tinine increased,)36.9 ( c)19.9 (y)-10 (anosis,)36.9 ( diabetes,)37 ( edema,)37 ( electrolyte abnormalities,)30 ( )]TJ 0.002 Tc 0.143 Tw 0 -1.05 Td [(hyperglycemia,)37.1 ( hyperkalemia,)37.2 ( hyperuricemia,)37.1 ( hypocalcemia,)37.2 ( hypoproteinemia,)37.1 ( LDH)2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(increased,)37.2 ( phosphorus decreased,)37.2 ( SGPT increased.)]TJ /T1_0 1 Tf -0.008 Tc 0.094 Tw 0 -1.68 Td [(Muscular )0.5 (Skeletal:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.619 0 Td [(Arthritis,)37.1 ( bone )0.5 (tenderness,)37.1 ( )0.5 (hypertonia,)37 ( )0.5 (joint )0.5 (disorder)74.1 (,)37 ( )0.5 (leg )0.5 (cramps,)29 ( )]TJ -0.017 Tc 0.048 Tw -7.619 -1.05 Td [(my)-9.8 (algia,)37.2 ( my)-9.8 (asthenia,)37.2 ( periosteal disorder)74.2 (.)]TJ /T1_0 1 Tf -0.014 Tc 0.064 Tw 0 -1.68 Td [(Ner)-17.9 (vous )0.5 (System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.795 0 Td [(Abnormal thinking,)37 ( )0.5 (a)-9.9 (gita)-9.9 (tion,)37 ( )0.5 (amnesia,)37.1 ( anxiety)55.1 (,)37.1 ( causalgia,)37 ( )0.5 (circumoral)-14 ( )]TJ -0.004 Tc 0.115 Tw -6.795 -1.05 Td [(paresthesia,)36.8 ( confusion,)36.8 ( depression,)36.7 ( euphoria,)36.8 ( hyperesthesia,)36.8 ( insomnia,)36.8 ( ner)-18.1 (vousness,)33 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td [(neuralgia,)37.2 ( neuritis,)37.2 ( neuropa)-9.7 (thy)55.2 (,)37.2 ( paresthesia,)37.2 ( peripheral neuritis,)37.2 ( psychosis.)]TJ /T1_0 1 Tf -0.012 Tc 0.077 Tw 0 -1.68 Td [(Respirator)-18.4 (y System:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 8.17 0 Td [(Cough,)36.6 ( emphysema,)36.5 ( epistaxis,)36.6 ( pulmonar)-18.4 (y embolus,)36.5 ( rales,)36.6 ( upper)-12 ( )]TJ -0.017 Tc 0.048 Tw -8.17 -1.05 Td [(respira)-9.8 (tor)-17.8 (y infection,)37.2 ( voice altera)-9.8 (tion.)]TJ /T1_0 1 Tf -0.021 Tc 0.036 Tw 0 -1.68 Td (Skin and Appendages:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 8.798 0 Td [(Acne,)36.9 ( alopecia,)36.8 ( dr)-18.2 (y skin,)36.8 ( eczema)-10.1 (tous rash,)36.8 ( exfolia)-10.1 (tive derma)-10.1 (titis,)16 ( )]TJ 0.008 Tc 0.171 Tw -8.798 -1.05 Td [(i)0.5 (c)0.5 (ht)0.5 (h)0.5 (y)0.5 (os)0.5 (i)0.5 (s)0.5 (,)37.4 ( p)0.5 (er)0.5 (i)0.5 (f)0.5 (o)0.5 (ll)0.5 (i)0.5 (cu)0.5 (l)0.5 (a)0.5 (r)0.5 ( t)0.5 (h)0.5 (ic)0.5 (k)0.5 (e)0.5 (n)0.5 (in)0.5 (g)0.5 (,)37.4 ( s)0.5 (k)0.5 (in)0.5 ( ne)0.5 (c)0.5 (r)0.5 (o)0.5 (si)0.5 (s)0.5 (,)37.4 ( s)0.5 (eb)0.5 (o)0.5 (r)0.5 (r)0.5 (he)0.5 (a)0.5 (,)37.5 ( s)-9.5 (w)0.5 (e)0.5 (a)-9.6 (t)0.5 (i)0.5 (n)0.5 (g,)37.5 ( ur)0.5 (t)0.5 (i)0.5 (c)0.5 (ar)0.5 (i)0.5 (a)0.5 (,)45 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td (vesiculobullous rash.)Tj /T1_0 1 Tf 0 -1.68 Td (Special Senses:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.288 0 Td [(Amblyopia,)37.2 ( deafness,)37.2 ( dr)-17.8 (y eye,)37.2 ( eye pain,)37.2 ( tinnitus.)]TJ /T1_0 1 Tf -0.002 Tc 0.002 Tw -6.288 -1.68 Td (Urogenital:)Tj /T1_1 1 Tf 0.122 Tw /Span<>> BDC ( )Tj EMC 4.617 0 Td [(Decreased crea)-9.7 (tinine c)20.3 (learance,)37.3 ( hema)-9.6 (turia,)37.3 ( orchitis,)37.3 ( proteinuria,)37.3 ( pyuria,)35 ( )]TJ -0.017 Tc 0.048 Tw -4.617 -1.05 Td [(urinar)-17.7 (y frequenc)20.2 (y)55.2 (.)]TJ /T1_0 1 Tf 0 -1.833 Td [(Other Adverse Reactions Obser)-17.8 (ved in HIV)18.2 (-seropositive P)24.1 (atients)]TJ /T1_1 1 Tf -0.015 Tc 0.06 Tw 0 -1.545 Td [(In addition to controlled c)20.4 (linical trials,)37.4 ( )37.3 (THALOMID has been used in uncontrolled studies)-15 ( )]TJ -0.001 Tc 0.129 Tw 0 -1.05 Td [(in 145 pa)-10 (tients.)37 ( Less frequent adverse reactions tha)-10 (t ha)-10 (ve been reported in these)-1 ( )]TJ -0.012 Tc 0.076 Tw 0 -1.05 Td [(HIV)17.7 (-seropositive pa)-10.4 (tients trea)-10.4 (ted with )36.9 (THALOMID were grouped into a smaller number)-12 ( )]TJ -0.009 Tc 0.089 Tw 0 -1.05 Td [(of standardized ca)-10.1 (tegories using modi\036ed COST)54.9 (AR)17.9 (T dictionar)-18 (y/terminolog)-10 (y and these)-9 ( )]TJ -0.002 Tc 0.126 Tw 0 -1.05 Td [(ca)-10.2 (tegories are used in the listing belo)-10.2 (w)36.7 (.)36.7 ( )37.3 (Adverse reactions tha)-10.3 (t ha)-10.3 (ve alread)-10.3 (y been)-2 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.05 Td [(inc)20.1 (luded in the tables and narra)-9.9 (tive above,)37.1 ( or tha)-9.9 (t are too general to be informa)-9.9 (tive are)-16 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.05 Td (not listed.)Tj /T1_2 1 Tf 0 Tc 0 Tw 0.233 85.34 Td (\()Tj -0.017 Tc 0.017 Tw 0.224 0 Td (Continued\))Tj ET endstream endobj 5 0 obj </LastModified/NumberofPages 1/OriginalDocumentID/PageTransformationMatrixList<>/PageUIDList<>/PageWidthList<>>>>>/Resources<>/Font<>/ProcSet[/PDF/Text]>>/TrimBox[0.0 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S Q q 1 0 0 1 178.11 607.5627 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 607.5627 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 575.307 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 575.307 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 575.307 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 650.5704 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 650.5704 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 650.5704 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 639.8185 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 639.8185 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 639.8185 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 618.3146 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 618.3146 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 618.3146 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 596.8108 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 596.8108 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 596.8108 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 586.0589 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 178.11 586.0589 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 586.0589 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.23 693.7361 cm 0 0 m 36.88 0 l S Q q 1 0 0 1 141.48 672.5742 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 178.11 693.7361 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 672.5742 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 214.74 693.7361 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 672.5742 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 251.37 693.7361 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 672.5742 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 141.48 672.3242 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 672.3242 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 672.3242 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 672.3242 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 661.5723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 178.11 661.5723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 141.48 661.3223 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 650.8204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 650.8204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 650.5704 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 640.0685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 640.0685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 639.8185 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 629.3165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 629.3165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 629.0665 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 618.5646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 618.5646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 618.3146 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 607.8127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 607.8127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 607.5627 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 597.0608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 597.0608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 596.8108 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 586.3089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 586.3089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 586.0589 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 575.557 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 575.557 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 575.307 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 564.8051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 564.8051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.48 543.5513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 178.11 543.5513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 214.74 661.5723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 251.37 661.5723 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 214.74 661.3223 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 650.8204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 650.8204 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 650.5704 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 640.0685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 640.0685 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 639.8185 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 629.3165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 629.3165 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 629.0665 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 618.5646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 618.5646 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 618.3146 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 607.8127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 607.8127 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 607.5627 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 597.0608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 597.0608 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 596.8108 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 586.3089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 586.3089 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 586.0589 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 575.557 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 575.557 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 575.307 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 564.8051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 564.8051 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 543.5513 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 251.37 543.5513 cm 0 0 m 0 10.002 l S Q 1 w q 1 0 0 1 36 543.0513 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.48 543.0513 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 543.0513 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 543.0513 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 543.0513 cm 0 0 m 36.63 0 l S Q 0.5 w q 1 0 0 1 36 513.1393 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.48 513.1393 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 513.1393 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 513.1393 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 513.1393 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 36 564.5551 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.48 564.5551 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 141.48 554.0532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 178.11 564.5551 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 554.0532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.74 564.5551 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 554.0532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 251.37 564.5551 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 554.0532 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 36 553.8032 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.48 553.8032 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 178.11 553.8032 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 214.74 553.8032 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 251.37 553.8032 cm 0 0 m 36.63 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.01 Tc 0.085 Tw 8 0 0 8 36 727.248 Tm [(T)81.2 (a)7.2 (b)7.2 (l)7.2 (e)7.2 ( )44.3 (1)7.2 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Adverse Reactions Reported in \03610% of P)23.9 (atients in the THALOMID/)]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(De)10.2 (xamethasone Arm \(Study 1 - Safety P)24.2 (opulation; N=204\))]TJ -0.012 Tc 7.6 0 0 8 36 684.4242 Tm (Body System)Tj 0 Tc 0 Tw 7.6 0 0 8 74.5314 684.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 36 675.9242 Tm (Adverse Reaction)Tj 16.382 3.739 Td [(Thal + De)10.3 (x*)]TJ 0 Tc 0 Tw 7.6 0 0 8 195.7189 705.8361 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 166.2056 697.3361 Tm (\(N=102\))Tj 0.048 Tw 9.074 1.062 Td [(De)10.2 (x Alone*)]TJ 0 Tc 0 Tw 7.6 0 0 8 267.8204 705.8361 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 239.5906 697.3361 Tm (\(N=102\))Tj 0.048 Tw -12.495 -1.614 Td (All Grades)Tj 0 Tc 0 Tw 7.6 0 0 8 174.9613 684.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 151.7802 675.9242 Tm (n \(%\))Tj 3.967 1.062 Td (Grade 3/4)Tj 0 Tc 0 Tw 7.6 0 0 8 210.9233 684.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 188.4102 675.9242 Tm (n \(%\))Tj 3.879 1.062 Td (All Grades)Tj 0 Tc 0 Tw 7.6 0 0 8 248.2213 684.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 225.0402 675.9242 Tm (n \(%\))Tj 3.983 1.062 Td (Grade 3/4)Tj 0 Tc 0 Tw 7.6 0 0 8 284.3083 684.4242 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 261.7952 675.9242 Tm (n \(%\))Tj 0 Tc 0 Tw /Span<>> BDC -29.71 -1.51 Td ( )Tj EMC -0.012 Tc 0.012 Tw 0.592 0 Td [(P)24.2 (ain)]TJ /T1_1 1 Tf 0.048 Tw 14.388 0 Td (64 \(63\))Tj 4.82 0 Td (10 \(10\))Tj 4.82 0 Td (66 \(65\))Tj 4.836 0 Td (15 \(15\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(My)-9.8 (algia)]TJ 0.048 Tw 14.98 0 Td (17 \(17\))Tj 5.288 0 Td (0 \(0\))Tj 4.352 0 Td (14 \(14\))Tj 5.304 0 Td (1 \(1\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Arthralgia)Tj 0.048 Tw 14.98 0 Td (13 \(13\))Tj 5.288 0 Td (0 \(0\))Tj 4.352 0 Td (10 \(10\))Tj 5.304 0 Td (2 \(2\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Pulmonar)-17.8 (y)]TJ /T1_1 1 Tf 0.048 Tw 14.98 0 Td (52 \(51\))Tj 4.82 0 Td (19 \(19\))Tj 4.82 0 Td (51 \(50\))Tj 4.836 0 Td (20 \(20\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC (Dyspnea)Tj 0.048 Tw 14.98 0 Td (43 \(42\))Tj 4.82 0 Td (13 \(13\))Tj 4.82 0 Td (32 \(31\))Tj 4.836 0 Td (15 \(15\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(Dermatolog)-9.8 (y/Skin)]TJ /T1_1 1 Tf 0.048 Tw 14.98 0 Td (48 \(47\))Tj 5.288 0 Td (5 \(5\))Tj 4.352 0 Td (35 \(34\))Tj 5.304 0 Td (2 \(2\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Rash/desquama)-9.8 (tion)]TJ 0.048 Tw 14.98 0 Td (31 \(30\))Tj 5.288 0 Td (4 \(4\))Tj 4.352 0 Td (18 \(18\))Tj 5.304 0 Td (2 \(2\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Dr)-17.8 (y )316.2 (skin)]TJ 0.048 Tw 14.98 0 Td (21 \(21\))Tj 5.288 0 Td (0 \(0\))Tj 4.352 0 Td (11 \(11\))Tj 5.304 0 Td (0 \(0\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Hepatic)Tj /T1_1 1 Tf 0.048 Tw 14.98 0 Td (47 \(46\))Tj 5.288 0 Td (7 \(7\))Tj 4.352 0 Td (45 \(44\))Tj 5.304 0 Td (4 \(4\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Bilirubin)Tj 0.048 Tw 14.98 0 Td (14 \(14\))Tj 5.288 0 Td (2 \(2\))Tj 4.352 0 Td (10 \(10\))Tj 5.304 0 Td (2 \(2\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Musculoskeletal)Tj /T1_1 1 Tf 0.048 Tw 14.98 0 Td (42 \(41\))Tj 5.288 0 Td (9 \(9\))Tj 4.352 0 Td (41 \(40\))Tj 4.836 0 Td (14 \(14\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(Musc)20.2 (le )316.2 (weakness)]TJ 0.048 Tw 14.98 0 Td (41 \(40\))Tj 5.288 0 Td (6 \(6\))Tj 4.352 0 Td (38 \(37\))Tj 4.836 0 Td (13 \(13\))Tj 0.008 Tc 0.147 Tw -29.456 -1.479 Td (*)Tj /Span<>> BDC 0.34 0 Td ( )Tj EMC 0.318 0 Td [(T)74.3 (rea)-9.6 (tment-emergent adverse reactions reported in \03710% of pa)-9.6 (tients in )37.2 (THALOMID/)]TJ -0.004 Tc 0.091 Tw 0 -1.062 Td [(dexamethasone arm )0.5 (and )0.5 (with a )0.5 (\0371% )0.5 (difference in )0.5 (the )37.4 (THALOMID/dexamethasone )0.5 (arm)-4 ( )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td (compared to the dexamethasone alone arm.)Tj -0.016 Tc 0.06 Tw 8 0 0 8 36.0002 496.657 Tm [(The safety analysis in Stud)-9.7 (y 2 was conducted on 466 pa)-9.7 (tients who received trea)-9.7 (tment.)21 ( )]TJ 0.011 Tc 0.19 Tw 0 -1.044 Td [(T)73.9 (able )0.5 (2 )0.5 (lists )0.5 (the )0.5 (most )0.5 (common )0.5 (adverse )0.5 (reactions )0.5 (\(\03710%\) )0.6 (tha)-10.1 (t )0.5 (were )0.5 (obser)-18 (ved.)48 ( )]TJ -0.008 Tc 0.095 Tw 0 -1.044 Td [(T)73.9 (able )0.6 (3 )0.5 (lists )0.5 (the )0.5 (most )0.5 (common )0.6 (Grade )0.6 (3/4 )0.6 (adverse )0.5 (reactions )0.6 (\(occurring )0.5 (a)-10.1 (t )0.5 (>2%\) )0.5 (tha)-10 (t)-8 ( )]TJ -0.004 Tc 0.117 Tw 0 -1.044 Td [(were )0.5 (obser)-18.4 (ved.)36.5 ( )37.5 (The )0.5 (adverse )0.5 (reactions )0.5 (most )0.5 (often )0.5 (reported )0.5 (by )0.5 (pa)-10.4 (tients trea)-10.4 (ted )0.5 (with)-4 ( )]TJ 0.003 Tc 0.147 Tw 0 -1.044 Td [(THALOMID/dexamethasone were constipa)-9.7 (tion,)37.4 ( peripheral edema,)37.4 ( tremor)74.3 (,)37.4 ( asthenia,)40 ( )]TJ -0.011 Tc 0.079 Tw 0 -1.044 Td [(dizziness and fa)-10 (tigue.)37 ( )37 (Adverse reactions with a frequenc)20 (y a)-10 (t least 2-fold higher in the)-11 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.044 Td [(THALOMID/dexamethasone group than in the placebo/dexamethasone group inc\ )20.3 (lude)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td [(constipa)-9.8 (tion,)37.2 ( tremor)74.2 (,)37.2 ( deep vein thrombosis and peripheral sensor)-17.8 (y neuropa)-9.8 (thy)55.2 (.)]TJ 0.006 Tc 0.165 Tw 0 -1.674 Td [(T)73.8 (wenty-six percent of pa)-10.1 (tients \(121/466\) discontinued due to adverse reactions;)6 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.044 Td [(37% \(86/234\) from the )36.9 (THALOMID/dexamethasone arm and 15% \(35/232\) from the)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.044 Td (placebo/dexamethasone arm.)Tj ET /GS1 gs q 1 0 0 1 36.0002 319.704 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 308.9521 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 298.2002 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 287.4482 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 276.6963 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 265.9444 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 222.9368 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 201.4329 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 179.9291 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 169.1772 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 255.1925 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 244.4406 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 233.6887 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 212.1848 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 190.681 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 158.4253 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 147.6734 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 136.9214 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 126.1695 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 106.9176 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 96.1657 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 36.0002 85.4138 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.4803 358.2078 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 319.954 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 141.4803 319.704 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 309.2021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 308.9521 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 298.4502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 298.2002 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 287.6982 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 287.4482 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 276.9463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 276.6963 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 266.1944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 265.9444 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 255.4425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 255.1925 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 244.6906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 244.4406 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 233.9387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 233.6887 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 223.1868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 222.9368 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 212.4348 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 212.1848 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 201.6829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 201.4329 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 190.931 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 190.681 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 180.1791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 179.9291 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 169.4272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 169.1772 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 158.6753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 158.4253 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 147.9234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 147.6734 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 137.1714 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 136.9214 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 126.4195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 126.1695 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 107.1676 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 141.4803 106.9176 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 96.4157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 96.1657 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 85.6638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 141.4803 85.4138 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 75.1619 cm 0 0 m 0 10.002 l S Q q 1 0 0 1 141.4803 339.2059 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 36.0002 338.9559 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.4803 338.9559 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 141.4803 358.4578 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 36.0002 358.2078 cm 0 0 m 105.48 0 l S Q 1 w q 1 0 0 1 36.0002 379.6197 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.4803 379.6197 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 36.0002 74.6619 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.4803 74.6619 cm 0 0 m 73.26 0 l S Q 0.5 w q 1 0 0 1 36.0002 36.25 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 141.4803 36.25 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 36.25 cm 0 0 m 73.26 0 l S Q 1 w q 1 0 0 1 214.7402 379.6197 cm 0 0 m 73.26 0 l S Q 0.5 w q 1 0 0 1 214.7402 358.4578 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 214.7402 358.2078 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 339.2059 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 214.7402 338.9559 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 319.954 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 214.7402 319.704 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 309.2021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 308.9521 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 298.4502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 298.2002 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 287.6982 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 287.4482 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 276.9463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 276.6963 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 266.1944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 265.9444 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 255.4425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 255.1925 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 244.6906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 244.4406 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 233.9387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 233.6887 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 223.1868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 222.9368 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 212.4348 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 212.1848 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 201.6829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 201.4329 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 190.931 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 190.681 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 180.1791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 179.9291 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 169.4272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 169.1772 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 158.6753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 158.4253 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 147.9234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 147.6734 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 137.1714 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 136.9214 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 126.4195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 126.1695 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 107.1676 cm 0 0 m 0 18.752 l S Q q 1 0 0 1 214.7402 106.9176 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 96.4157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 96.1657 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 85.6638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 214.7402 85.4138 cm 0 0 m 73.26 0 l S Q q 1 0 0 1 214.7402 75.1619 cm 0 0 m 0 10.002 l S Q 1 w q 1 0 0 1 214.7402 74.6619 cm 0 0 m 73.26 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.01 Tc 0.085 Tw 8 0 0 8 36.0003 391.7197 Tm [(T)81.2 (a)7.2 (b)7.2 (l)7.2 (e)7.2 ( )44.3 (2)7.2 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Adverse Reactions Reported in \03610% of P)23.9 (atients in the THALOMID/)]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(De)10.2 (xamethasone Arm \(Study 2 - Safety P)24.2 (opulation; N=466\))]TJ -0.012 Tc 7.6 0 0 8 36.0003 370.3078 Tm (Body System)Tj 0 Tc 0 Tw 7.6 0 0 8 74.5316 370.3078 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 36.0003 361.8078 Tm (Adverse Reaction)Tj 15.093 1.062 Td [(Thal/De)10.2 (x \(N=234\)*)]TJ 0 Tc 0 Tw 7.6 0 0 8 205.5108 370.3078 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 170.0954 361.8078 Tm (n \(%\))Tj 6.401 1.062 Td [(Placebo/De)10.2 (x \(N=232\)*)]TJ 3.255 -1.062 Td (n \(%\))Tj -27.3 -1.479 Td [(P)24.2 (atients with at least 1 Adverse)-12 ( )]TJ 0.012 Tw 0 -1.062 Td (Reaction)Tj 0.048 Tw 17.101 0.531 Td (233 \(99\))Tj 9.656 0 Td (230 \(99\))Tj -26.757 -1.875 Td [(General Disorders and)-12 ( )]TJ 0 -1.062 Td (Administration Site Conditions)Tj 17.101 0.531 Td (176 \(75\))Tj 9.656 0 Td (149 \(64\))Tj /T1_1 1 Tf /Span<>> BDC -26.757 -1.875 Td ( )Tj EMC 0.592 0 Td (Edema peripheral)Tj 16.798 0 Td (80 \(34\))Tj 9.656 0 Td (57 \(25\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC (Asthenia)Tj 0.048 Tw 17.39 0 Td (56 \(24\))Tj 9.656 0 Td (47 \(20\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC [(F)20.2 (a)-9.8 (tigue)]TJ 0.048 Tw 17.39 0 Td (50 \(21\))Tj 9.656 0 Td (36 \(16\))Tj /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC 0.592 0 Td (Edema NOS)Tj 16.798 0 Td (31 \(13\))Tj 9.89 0 Td (19 \(8\))Tj /T1_0 1 Tf -27.28 -1.344 Td (Gastrointestinal Disorders)Tj 17.101 0 Td (162 \(69\))Tj 9.656 0 Td (149 \(64\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.757 -1.344 Td ( )Tj EMC [(Constipa)-9.8 (tion)]TJ 0.048 Tw 17.156 0 Td (116 \(50\))Tj 9.89 0 Td (49 \(21\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC (Nausea)Tj 0.048 Tw 17.39 0 Td (30 \(13\))Tj 9.656 0 Td (27 \(12\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC (Dyspepsia)Tj 0.048 Tw 17.39 0 Td (27 \(11\))Tj 9.89 0 Td (21 \(9\))Tj /T1_0 1 Tf -27.28 -1.344 Td [(Ner)-17.7 (vous System Disorders)]TJ 17.101 0 Td (161 \(69\))Tj 9.656 0 Td (138 \(60\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.757 -1.344 Td ( )Tj EMC [(T)74.2 (remor)]TJ 0.048 Tw 17.39 0 Td (62 \(26\))Tj 9.656 0 Td (29 \(12\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC (Dizziness)Tj 0.048 Tw 17.39 0 Td (51 \(23\))Tj 9.656 0 Td (32 \(14\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC [(P)18.2 (aresthesia)]TJ 0.048 Tw 17.39 0 Td (27 \(12\))Tj 9.89 0 Td (15 \(6\))Tj /Span<>> BDC -27.28 -1.344 Td ( )Tj EMC 0.592 0 Td [(P)18.2 (eripheral sensor)-17.8 (y neuropa)-9.8 (thy)]TJ 16.798 0 Td (24 \(10\))Tj 9.89 0 Td (12 \(5\))Tj /T1_0 1 Tf -27.28 -1.344 Td (Infections and Infestations)Tj 17.101 0 Td (139 \(59\))Tj 9.656 0 Td (138 \(60\))Tj /T1_1 1 Tf /Span<>> BDC -26.757 -1.344 Td ( )Tj EMC 0.592 0 Td (Pneumonia NOS)Tj 16.798 0 Td (35 \(15\))Tj 9.656 0 Td (28 \(12\))Tj /T1_0 1 Tf -27.046 -1.344 Td (Psychiatric Disorders)Tj 17.335 0 Td (90 \(38\))Tj 9.656 0 Td (97 \(42\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.991 -1.344 Td ( )Tj EMC (Anxiety)Tj 0.048 Tw 17.39 0 Td (27 \(12\))Tj 9.656 0 Td (22 \(10\))Tj 0.364 Tw /Span<>> BDC -27.046 -1.344 Td ( )Tj EMC (Depression)Tj 0.048 Tw 17.39 0 Td (24 \(10\))Tj 9.89 0 Td (19 \(8\))Tj /T1_0 1 Tf -27.28 -1.344 Td [(Metabolism and Nutrition)-11.9 ( )]TJ 0.012 Tw 0 -1.062 Td (Disorders)Tj 0.048 Tw 17.335 0.531 Td (96 \(41\))Tj 9.656 0 Td (89 \(38\))Tj /T1_1 1 Tf /Span<>> BDC -26.991 -1.875 Td ( )Tj EMC 0.592 0 Td (Hyperglycemia NOS)Tj 16.798 0 Td (36 \(15\))Tj 9.656 0 Td (32 \(14\))Tj /T1_0 1 Tf -27.046 -1.344 Td [(V)18.2 (ascular Disorders)]TJ 17.335 0 Td (92 \(39\))Tj 9.656 0 Td (53 \(23\))Tj /T1_1 1 Tf /Span<>> BDC -26.991 -1.344 Td ( )Tj EMC 0.592 0 Td (Deep vein thrombosis)Tj 16.798 0 Td (30 \(13\))Tj 10.124 0 Td (4 \(2\))Tj 0.043 Tw -27.514 -1.479 Td (*)Tj /Span<>> BDC ( )Tj EMC 0.658 0 Td [(All adverse reactions reported in \03710% of pa)-9.8 (tients in )37 (THALOMID/dexamethasone arm and)-11.9 ( )]TJ -0.007 Tc 0.074 Tw 0 -1.062 Td [(with )0.5 (a )0.5 (\0371% )0.5 (difference )0.5 (in )0.5 (proportion )0.5 (of )0.5 (pa)-9.9 (tients )0.5 (between )0.5 (the )37.5 (THALOMID/dexamethasone)-7 ( )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td (arm compared to the placebo/dexamethasone arm.)Tj -0.115 Tw -0.658 -1.062 Td (NOS)Tj /Span<>> BDC ( )Tj EMC (=)Tj /Span<>> BDC ( )Tj EMC [(not )-162.8 (otherwise )-162.8 (specified.)]TJ /T1_2 1 Tf 0 Tc 0 Tw 8 0 0 8 37.8603 718.704 Tm (\()Tj -0.017 Tc 0.017 Tw 0.224 0 Td (Continued\))Tj ET 0.505 w /GS1 gs q 1 0 0 1 324 673.8995 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 663.04 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 652.1806 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 632.7361 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 621.8767 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 611.0173 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 589.2985 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 567.5796 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 535.0013 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 600.1578 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 578.439 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 524.1418 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 513.2824 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 502.423 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 491.5635 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 480.7041 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 469.8447 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 458.9852 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 439.5408 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 428.6814 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 409.2369 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 398.3775 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 387.5181 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 376.6586 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 365.7992 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 324 354.9398 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 684.7589 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 673.8995 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 663.2925 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 663.04 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 652.4331 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 652.1806 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 632.9886 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 436.5 632.7361 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 622.1292 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 621.8767 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 611.2698 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 611.0173 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 600.4103 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 600.1578 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 589.5509 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 589.2985 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 578.6915 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 578.439 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 567.832 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 567.5796 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 556.9727 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 535.2538 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 535.0013 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 524.3943 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 524.1418 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 513.5349 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 513.2824 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 502.6755 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 502.423 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 491.816 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 491.5635 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 480.9566 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 480.7041 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 470.0972 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 469.8447 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 459.2377 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 458.9852 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 439.7933 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 436.5 439.5408 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 428.9339 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 428.6814 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 409.4894 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 436.5 409.2369 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 398.63 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 398.3775 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 387.7706 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 387.5181 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 376.9111 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 376.6586 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 366.0517 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 365.7992 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 355.1923 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 354.9398 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 344.5853 cm 0 0 m 0 10.102 l S Q q 1 0 0 1 436.5 674.152 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 436.5 685.0114 cm 0 0 m 0 29.453 l S Q q 1 0 0 1 324 684.7589 cm 0 0 m 112.5 0 l S Q 1.01 w q 1 0 0 1 324 714.9699 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 714.9699 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 324 344.0803 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 344.0803 cm 0 0 m 69.75 0 l S Q 0.505 w q 1 0 0 1 324 305.2843 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 305.2843 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 305.2843 cm 0 0 m 69.75 0 l S Q 1.01 w q 1 0 0 1 506.25 714.9699 cm 0 0 m 69.75 0 l S Q 0.505 w q 1 0 0 1 506.25 685.0114 cm 0 0 m 0 29.453 l S Q q 1 0 0 1 506.25 684.7589 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 674.152 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 673.8995 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 663.2925 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 663.04 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 652.4331 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 652.1806 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 632.9886 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 506.25 632.7361 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 622.1292 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 621.8767 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 611.2698 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 611.0173 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 600.4103 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 600.1578 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 589.5509 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 589.2985 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 578.6915 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 578.439 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 567.832 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 567.5796 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 556.9727 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 535.2538 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 535.0013 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 524.3943 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 524.1418 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 513.5349 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 513.2824 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 502.6755 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 502.423 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 491.816 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 491.5635 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 480.9566 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 480.7041 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 470.0972 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 469.8447 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 459.2377 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 458.9852 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 439.7933 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 506.25 439.5408 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 428.9339 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 428.6814 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 409.4894 cm 0 0 m 0 18.939 l S Q q 1 0 0 1 506.25 409.2369 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 398.63 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 398.3775 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 387.7706 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 387.5181 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 376.9111 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 376.6586 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 366.0517 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 365.7992 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 355.1923 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 354.9398 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 344.5853 cm 0 0 m 0 10.102 l S Q 1.01 w q 1 0 0 1 506.25 344.0803 cm 0 0 m 69.75 0 l S Q 0.505 w q 1 0 0 1 324 556.7201 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 556.7201 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 436.5 546.1132 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 506.25 556.7201 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 546.1132 cm 0 0 m 0 10.354 l S Q q 1 0 0 1 324 545.8607 cm 0 0 m 112.5 0 l S Q q 1 0 0 1 436.5 545.8607 cm 0 0 m 69.75 0 l S Q q 1 0 0 1 506.25 545.8607 cm 0 0 m 69.75 0 l S Q BT /GS2 gs /T1_0 1 Tf -0.004 Tc 0.112 Tw 8.08 0 0 8.08 324 727.1909 Tm [(T)87.2 (a)13.2 (b)13.2 (l)13.2 (e)13.2 ( )77.2 (3)13.2 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Grade 3/4 Adverse Reactions Reported in >2% of P)24.3 (atients in the)-4 ( )]TJ -0.025 Tc 0.036 Tw 0 -1.062 Td [(THALOMID/De)9.7 (xamethasone Arm \(Study 2 - Safety P)23.6 (opulation; N=466\))]TJ -0.012 Tc 0.048 Tw 7.676 0 0 8.08 324 696.9799 Tm (Body System)Tj 0 Tc 0 Tw 7.676 0 0 8.08 362.9166 696.9799 Tm ( )Tj -0.012 Tc 0.048 Tw 7.676 0 0 8.08 324 688.3949 Tm (Adverse Reaction)Tj 0.012 Tw 16.265 2.125 Td [(THALOMID/De)10.2 (x)-11.9 ( )]TJ 1.18 -1.062 Td (\(N=234\)*)Tj 0 Tc 0 Tw 7.676 0 0 8.08 484.8484 696.9799 Tm ( )Tj -0.012 Tc 0.048 Tw 7.676 0 0 8.08 463.28 688.3949 Tm (n \(%\))Tj 5.848 1.062 Td [(Placebo/De)10.2 (x \(N=232\)*)]TJ 3.255 -1.062 Td (n \(%\))Tj -27.248 -1.479 Td (Infections and Infestations)Tj 17.836 0 Td (50 \(21\))Tj 9.103 0 Td (36 \(16\))Tj /T1_1 1 Tf /Span<>> BDC -26.939 -1.344 Td ( )Tj EMC 0.592 0 Td (Pneumonia NOS)Tj 17.533 0 Td (17 \(7\))Tj 9.103 0 Td (14 \(6\))Tj /Span<>> BDC -27.228 -1.344 Td ( )Tj EMC 0.592 0 Td (Bronchopneumonia NOS)Tj 17.767 0 Td (7 \(3\))Tj 9.103 0 Td (3 \(1\))Tj /T1_0 1 Tf -27.462 -1.344 Td [(General Disorders and)-12 ( )]TJ 0 -1.062 Td (Administration Site Conditions)Tj 17.836 0.531 Td (44 \(19\))Tj 9.103 0 Td (26 \(11\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.939 -1.875 Td ( )Tj EMC (Asthenia)Tj 0.048 Tw 18.125 0 Td (11 \(5\))Tj 9.337 0 Td (4 \(2\))Tj /T1_0 1 Tf -27.462 -1.344 Td (Metabolism and Nutrition Disorders)Tj 17.836 0 Td (33 \(14\))Tj 9.103 0 Td (34 \(15\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.939 -1.344 Td ( )Tj EMC (Hypokalemia)Tj 0.048 Tw 18.359 0 Td (7 \(3\))Tj 9.103 0 Td (3 \(1\))Tj /T1_0 1 Tf -27.462 -1.344 Td [(Ner)-17.7 (vous System Disorders)]TJ 17.836 0 Td (47 \(20\))Tj 9.337 0 Td (20 \(9\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -27.173 -1.344 Td ( )Tj EMC (Syncope)Tj 0.048 Tw 18.359 0 Td (8 \(3\))Tj 8.809 0 Td (1 \(<1\))Tj /Span<>> BDC -27.168 -1.344 Td ( )Tj EMC 0.592 0 Td [(P)18.2 (eripheral neuropa)-9.8 (thy NOS)]TJ 17.767 0 Td (8 \(3\))Tj 9.103 0 Td (0 \(0\))Tj /Span<>> BDC -27.462 -1.344 Td ( )Tj EMC 0.592 0 Td (Cerebrovascular accident)Tj 17.767 0 Td (6 \(3\))Tj 8.809 0 Td (1 \(<1\))Tj /T1_0 1 Tf -27.168 -1.344 Td (Cardiac Disorders)Tj 17.836 0 Td (35 \(15\))Tj 9.103 0 Td (27 \(11\))Tj /T1_1 1 Tf /Span<>> BDC -26.939 -1.344 Td ( )Tj EMC 0.592 0 Td [(Atrial fibrilla)-9.8 (tion)]TJ 17.533 0 Td (11 \(5\))Tj 9.337 0 Td (8 \(3\))Tj /Span<>> BDC -27.462 -1.344 Td ( )Tj EMC 0.592 0 Td (Myocardial ischemia)Tj 17.767 0 Td (6 \(3\))Tj 9.103 0 Td (2 \(1\))Tj /T1_0 1 Tf -27.462 -1.344 Td [(V)18.2 (ascular Disorders)]TJ 17.836 0 Td (42 \(18\))Tj 9.337 0 Td (14 \(6\))Tj /T1_1 1 Tf /Span<>> BDC -27.173 -1.344 Td ( )Tj EMC 0.592 0 Td (Deep vein thrombosis)Tj 17.299 0 Td (27 \(12\))Tj 9.571 0 Td (4 \(2\))Tj /T1_0 1 Tf -27.462 -1.344 Td (Gastrointestinal Disorders)Tj 17.836 0 Td (26 \(11\))Tj 9.103 0 Td (22 \(10\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -26.939 -1.344 Td ( )Tj EMC [(Constipa)-9.8 (tion)]TJ 0.048 Tw 18.359 0 Td (7 \(3\))Tj 9.103 0 Td (2 \(1\))Tj /T1_0 1 Tf 0.012 Tw -27.462 -1.344 Td (Investigations)Tj 0.048 Tw 18.07 0 Td (21 \(9\))Tj 9.103 0 Td (21 \(9\))Tj /T1_1 1 Tf /Span<>> BDC -27.173 -1.344 Td ( )Tj EMC 0.592 0 Td [(W)18.2 (eight increased)]TJ 17.767 0 Td (8 \(3\))Tj 9.103 0 Td (4 \(2\))Tj /T1_0 1 Tf -27.462 -1.344 Td [(Blood and L)37.2 (ymphatic System)-12 ( )]TJ 0.012 Tw 0 -1.062 Td (Disorders)Tj 0.048 Tw 17.836 0.531 Td (24 \(10\))Tj 9.337 0 Td (17 \(7\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -27.173 -1.875 Td ( )Tj EMC (Neutropenia)Tj 0.048 Tw 18.359 0 Td (8 \(3\))Tj 9.103 0 Td (6 \(3\))Tj /T1_0 1 Tf -27.462 -1.344 Td [(Respirator)-17.7 (y)55.2 (,)37.2 ( Thoracic,)37.2 ( and)-11.9 ( )]TJ 0 -1.062 Td (Mediastinal Disorders)Tj 17.836 0.531 Td (27 \(12\))Tj 9.337 0 Td (13 \(6\))Tj /T1_1 1 Tf /Span<>> BDC -27.173 -1.875 Td ( )Tj EMC 0.592 0 Td [(Pulmonar)-17.7 (y embolism)]TJ 17.533 0 Td (16 \(7\))Tj 9.337 0 Td (4 \(2\))Tj /T1_0 1 Tf -27.462 -1.344 Td (Psychiatric Disorders)Tj 18.07 0 Td (19 \(8\))Tj 9.337 0 Td (8 \(3\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -27.407 -1.344 Td ( )Tj EMC (Anxiety)Tj 0.048 Tw 18.359 0 Td (5 \(2\))Tj 9.103 0 Td (3 \(1\))Tj /Span<>> BDC -27.462 -1.344 Td ( )Tj EMC 0.592 0 Td [(Confusional sta)-9.8 (te)]TJ 17.767 0 Td (5 \(2\))Tj 9.103 0 Td (2 \(1\))Tj /T1_0 1 Tf -27.462 -1.344 Td (Ear and Labyrinth Disorders)Tj 18.304 0 Td (6 \(3\))Tj 9.103 0 Td (0 \(0\))Tj /T1_1 1 Tf 0.364 Tw /Span<>> BDC -27.407 -1.344 Td ( )Tj EMC [(V)18.2 (ertigo)]TJ 0.048 Tw 18.359 0 Td (5 \(2\))Tj 9.103 0 Td (0 \(0\))Tj 0.059 Tw -27.462 -1.479 Td (*)Tj /Span<>> BDC ( )Tj EMC 0.658 0 Td [(All Grade 3/4 adverse reactions with >2% of pa)-9.8 (tients in )37.1 (THALOMID/dexamethasone arm)-12 ( )]TJ 0 Tc 0.111 Tw 0 -1.062 Td [(and with a higher frequenc)19.6 (y in the )36.7 (THALOMID/dexamethasone arm compared to the )]TJ -0.012 Tc 0.048 Tw 0 -1.062 Td (placebo/dexamethasone arm.)Tj -0.115 Tw -0.658 -1.062 Td (NOS)Tj /Span<>> BDC ( )Tj EMC (=)Tj /Span<>> BDC ( )Tj EMC [(not )-162.8 (otherwise )-162.8 (specified.)]TJ /T1_0 1 Tf -0.017 Tc 0.048 Tw 8.08 0 0 8.08 324.0002 290.2204 Tm [(Less Common Adverse Reactions in Multiple Myeloma Controlled Clinical T)74.2 (rials)]TJ /T1_1 1 Tf -0.008 Tc 0.093 Tw 0 -1.54 Td [(In Stud)-9.8 (y 2,)37.2 ( )37 (THALOMID in combina)-9.8 (tion with dexamethasone in pa)-9.8 (tients with multiple)-7.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.045 Td [(myeloma,)37.2 ( the follo)-9.8 (wing adverse reactions not described above were reported*:)]TJ /T1_0 1 Tf 0.016 Tc 0.212 Tw 0 -1.672 Td [(Ga)0.5 (str)0.5 (oint)0.5 (est)0.5 (ina)0.5 (l )0.5 (d)0.5 (iso)0.5 (rder)0.5 (s:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 11.451 0 Td [(V)18.4 (o)0.5 (mit)0.5 (ing)0.5 ( )0.5 (NOS,)37.5 ( )0.5 (dr)-17.5 (y )0.5 (mo)0.5 (ut)0.5 (h,)37.4 ( )0.5 (pe)0.5 (ri)0.5 (ton)0.5 (iti)0.5 (s,)37.4 ( )0.5 (d)0.5 (ive)0.5 (rtic)0.5 (ula)0.5 (r)16 ( )]TJ -0.017 Tc 0.017 Tw -11.451 -1.045 Td [(perfora)-9.8 (tion)]TJ /T1_0 1 Tf -0.018 Tc 0.036 Tw 0 -1.579 Td [(Ner)-18.3 (vous system disorders:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 10.507 0 Td [(Somnolence,)36.7 ( hypoesthesia,)36.7 ( polyneuropa)-10.2 (thy NOS,)36.7 ( transient)-18 ( )]TJ -0.017 Tc 0.048 Tw -10.507 -1.045 Td [(ischemic a)-9.8 (ttack)]TJ /T1_0 1 Tf 0 -1.579 Td [(Respirator)-17.8 (y)55.2 (,)37.2 ( thoracic,)37.2 ( and mediastinal disorders:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 18.921 0 Td (Bronchitis NOS)Tj /T1_0 1 Tf -18.921 -1.579 Td (Psychiatric disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 8.626 0 Td [(Mood altera)-9.7 (tion NOS)]TJ /T1_0 1 Tf -8.626 -1.579 Td [(V)18.2 (ascular disorders:)]TJ /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.697 0 Td [(Hypotension NOS,)37.3 ( orthosta)-9.8 (tic hypotension)]TJ /T1_0 1 Tf -7.697 -1.579 Td (Cardiac disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.306 0 Td [(Brad)-9.7 (ycardia NOS)]TJ /T1_0 1 Tf -7.306 -1.579 Td (Eye disorders:)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 5.728 0 Td (Blurred vision)Tj -0.006 Tc 0.107 Tw -5.728 -1.672 Td (*)Tj /Span<>> BDC ( )Tj EMC 0.429 0 Td [(All )0.5 (adverse reactions with \0373% of pa)-10.5 (tients )0.5 (in )37.4 (THALOMID/dexamethasone arm and)-6 ( )]TJ -0.019 Tc 0.036 Tw -0.429 -1.045 Td [(with a \0371% difference in proportion of pa)-10.3 (tients between the )36.7 (THALOMID/dexamethasone)-19 ( )]TJ -0.013 Tc 0.067 Tw 0 -1.045 Td [(arm compared to the placebo/dex)0.5 (amethaso)0.5 (ne arm.)37.4 ( )37.3 (All grade 3/4 and serious adve)0.5 (rse)-13 ( )]TJ -0.022 Tc 0.035 Tw 0 -1.045 Td [(reac)0.5 (tions )0.5 (reporte)0.5 (d >2 )0.5 (pa)-9.6 (tient)0.5 (s in )37.4 (TH)0.5 (ALOMID/dex)0.5 (ametha)0.5 (sone a)0.5 (rm an)0.5 (d with )0.5 (a per)0.5 (centa)-9.6 (ge)-21.9 ( )]TJ -0.017 Tc 0.041 Tw 0 -1.045 Td [(higher in the )37 (THALOMID/dexamethasone arm compared to the placebo/dexamethasone)-17 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.045 Td [(arm ha)-9.8 (ve been considered for possible inc)20.2 (lusion.)37.2 ( In an)-9.9 (y cases medical judgment has)-12 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.045 Td [(been a)-9.8 (pplied for considera)-9.8 (tion of causality assessment.)]TJ /T1_0 1 Tf 0 -1.986 Td [(Adverse Reactions in Er)-17.8 (ythema Nodosum Leprosum \(ENL\) Clinical T)74.1 (rials)]TJ /T1_1 1 Tf -0.027 Tc 0.024 Tw 0 -1.54 Td [(T)73.7 (able 4 lists trea)-10.2 (tment-emergent signs and symptoms tha)-10.2 (t occurred in )36.6 (THALOMID-trea)-10.2 (ted)-27 ( )]TJ 0 Tc 0 Tw 8.08 0 0 8.08 576.0002 69.7597 Tm ( )Tj -0.017 Tc 0.056 Tw 8.08 0 0 8.08 324.0002 61.3198 Tm [(pa)-9.8 (tients )0.5 (in c)20.2 (linical trials in )0.5 (ENL.)37.2 ( )37.4 (The most common )0.5 (adverse reactions )0.5 (\(\037 10%\) reported)-17 ( )]TJ -0.002 Tc 0.124 Tw 0 -1.045 Td [(in pa)-10 (tients with ENL were somnolence,)37 ( rash,)37.1 ( headache.)37 ( Doses ranged from 50 to)-2 ( )]TJ -0.017 Tc 0.039 Tw 0 -1.045 Td [(300 mg/day)55.2 (.)37.2 ( )37.3 (All adverse reactions were mild to modera)-9.7 (te in severity)55.2 (,)37.2 ( and none resulted)-17 ( )]TJ 0.048 Tw 0 -1.045 Td [(in discontinua)-9.8 (tion.)]TJ ET endstream endobj 109 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q BT /GS1 gs /T1_0 1 Tf -0.017 Tc 0.017 Tw 8 0 0 8 36 727.248 Tm (5.9)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(Thromboc)10.2 (ytopenia)]TJ /T1_1 1 Tf -0.019 Tc 0.036 Tw -3.375 -1.61 Td [(Thromboc)19.6 (ytopenia,)36.6 ( inc)19.6 (luding Grade 3 or 4 occurrences,)36.6 ( has been reported in associa)-10.4 (tion)-19 ( )]TJ -0.017 Tc 0.05 Tw 0 -1.07 Td [(with the c)20.2 (linical use of )37.4 (THALOMID.)37.2 ( Monitor blood counts,)37.2 ( inc)20.2 (luding pla)-9.8 (telet counts.)37.2 ( Dose)-17 ( )]TJ -0.011 Tc 0.082 Tw 0 -1.07 Td [(reduction,)36.6 ( delay)54.6 (,)36.5 ( )0.5 (or discontinua)-10.4 (tion )0.5 (may )0.5 (be required.)36.5 ( )0.5 (Monitor for )0.5 (signs )0.5 (and )0.5 (symptoms)-11 ( )]TJ -0.006 Tc 0.105 Tw 0 -1.07 Td [(of bleeding inc)19.9 (luding petechiae,)37 ( epistaxis,)36.9 ( and gastrointestinal bleeding,)36.9 ( especially if)-5.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(concomitant medica)-9.8 (tion may increase the risk of bleeding.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.899 Td (5.10)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Increased HIV Viral Load)Tj /T1_1 1 Tf -0.009 Tc 0.087 Tw -3.375 -1.61 Td [(In a randomized,)37.4 ( placebo-controlled trial of thalidomide in an HIV)18.4 (-seropositive pa)-9.6 (tient)-9 ( )]TJ -0.013 Tc 0.067 Tw 0 -1.07 Td [(popula)-9.6 (tion,)37.2 ( plasma HIV RNA levels were found to increase \(median change)]TJ /Span<>> BDC ( )Tj EMC 27.23 0 Td (=)Tj /Span<>> BDC ( )Tj EMC 0.615 0 Td (0.42 log)Tj 0.013 Tw 5.6 0 0 5.6 282.6986 643.243 Tm (10)Tj 0 Tc 0 Tw 8 0 0 8 288 643.483 Tm ( )Tj -0.006 Tc 0.106 Tw -31.5 -1.07 Td [(copies HIV RNA/mL,)36.6 ( p)]TJ /Span<>> BDC ( )Tj EMC 8.238 0 Td (=)Tj /Span<>> BDC ( )Tj EMC 0.63 0 Td [(0.04 compared to placebo\).)36.6 ( )36.6 (A similar trend was obser)-18.4 (ved in)-6 ( )]TJ -0.003 Tc 0.119 Tw -8.868 -1.07 Td [(a second,)37 ( unpublished stud)-9.9 (y conducted in pa)-9.9 (tients who were HIV)18.1 (-seropositive.)37 ( )37.3 (The)-2.9 ( )]TJ -0.012 Tc 0.074 Tw 0 -1.07 Td [(c)20.1 (linical signi\036cance of this increase is unkno)-9.9 (wn.)37 ( Both studies were conducted prior to)-12 ( )]TJ -0.007 Tc 0.1 Tw 0 -1.07 Td [(a)-10.1 (vailability of highly active antiretroviral thera)-10.1 (py)54.9 (.)36.9 ( Until the c)19.9 (linical signi\036cance of this)-7 ( )]TJ -0.017 Tc 0.044 Tw 0 -1.07 Td [(\036nding is further understood,)37.3 ( in HIV)18.2 (-seropositive pa)-9.8 (tients,)37.1 ( viral load should be measured)-17 ( )]TJ 0.048 Tw 0 -1.07 Td [(after the \036rst and third months of trea)-9.7 (tment and ever)-17.8 (y 3 months thereafter)74.2 (.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.899 Td (5.11)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Bradycardia)Tj /T1_1 1 Tf 0.046 Tw -3.375 -1.61 Td [(Brad)-9.8 (ycardia in associa)-9.8 (tion with )36.6 (THALOMID use has been reported.)37.2 ( Cases of brad)-9.8 (ycardia)-17 ( )]TJ -0.013 Tc 0.068 Tw 0 -1.07 Td [(ha)-9.7 (ve been reported,)37.2 ( some required medical inter)-17.8 (ventions.)37.3 ( )37.3 (The c)20.2 (linical signi\036cance and)-13 ( )]TJ -0.008 Tc 0.096 Tw 0 -1.07 Td [(underlying etiolog)-10.3 (y of the brad)-10.3 (ycardia noted in some )37.1 (THALOMID-trea)-10.3 (ted pa)-10.3 (tients are)-8 ( )]TJ 0.095 Tw 0 -1.07 Td [(presently unkno)-10.1 (wn.)36.9 ( Monitor pa)-10.1 (tients for brad)-10.1 (ycardia and syncope.)36.8 ( Dose reduction or)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(discontinua)-9.8 (tion may be required.)]TJ -0.003 Tc 0.12 Tw 0 -1.79 Td [(Medica)-10.2 (tions kno)-10.2 (wn to decrease heart ra)-10.2 (te should be used with caution in pa)-10.2 (tients)-3 ( )]TJ -0.017 Tc 0.011 Tw 0 -1.07 Td (receiving THALOMID )Tj /T1_2 1 Tf 0.048 Tw 7.526 0 Td ([see Drug Interactio)Tj (ns \(7.2\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw -7.526 -1.899 Td (5.12)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Severe Cutaneous Reactions)Tj /T1_1 1 Tf 0.047 Tw -3.375 -1.61 Td [(Severe cutaneous reactions inc)20.2 (luding Stevens-Johnson syndrome \(SJS\),)37.2 ( toxic epidermal)-17 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.07 Td [(necrolysis \(TEN\),)37.2 ( and drug reaction with eosinophilia and systemic symptoms \(DRESS\))-12 ( )]TJ -0.017 Tc 0.049 Tw 0 -1.07 Td [(ha)-9.8 (ve been reported with )36.9 (THALOMID use.)37.2 ( DRESS may present with a cutaneous reaction)-17 ( )]TJ -0.004 Tc 0.116 Tw 0 -1.07 Td [(\(such as rash or exfolia)-10.3 (tive derma)-10.3 (titis\),)36.6 ( eosinophilia,)36.6 ( fever)73.6 (,)36.7 ( and/or lymphadenopa)-10.3 (thy)-3.9 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.07 Td [(with systemic complica)-9.8 (tions such as hepa)-9.8 (titis,)37.2 ( nephritis,)37.2 ( pneumonitis,)37.2 ( myocarditis,)37.2 ( and/)]TJ -0.004 Tc 0.115 Tw 0 -1.07 Td [(or pericarditis.)36.8 ( )36.9 (These events can be fa)-10.1 (tal.)36.9 ( )36.9 (THALOMID interruption or discontinua)-10.2 (tion)-4 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.07 Td [(s)0.5 (ho)0.5 (ul)0.5 (d)0.5 ( b)0.5 (e)0.5 ( c)0.5 (o)0.5 (ns)0.5 (id)0.5 (e)0.5 (re)0.5 (d)0.5 ( f)0.5 (o)0.5 (r )0.5 (Gr)0.5 (a)0.5 (de)0.5 ( )0.5 (2-)0.5 (3)0.5 ( s)0.5 (k)0.5 (in)0.5 ( r)0.5 (a)0.5 (sh)0.5 (.)37.4 ( )0.5 (D)0.5 (is)0.5 (c)0.5 (on)0.5 (t)0.5 (in)0.5 (ue)0.5 ( )37.4 (T)0.5 (H)0.5 (AL)0.5 (O)0.5 (MI)0.5 (D )0.5 (f)0.5 (or)0.5 ( )0.5 (Gr)0.5 (a)0.5 (de)0.5 ( )0.5 (4 )0.5 (r)0.5 (as)0.5 (h,)21 ( )]TJ -0.017 Tc 0.058 Tw 0 -1.07 Td [(exfolia)-9.8 (tive or bullous rash,)37.2 ( or for other severe cutaneous reactions such as SJS,)37.2 ( )37.2 (TEN,)37.2 ( or)-17 ( )]TJ 0.048 Tw 0 -1.07 Td [(DRESS,)37.2 ( and do not resume thera)-9.8 (py )]TJ /T1_2 1 Tf [([see Dosa)-9.7 (ge and )37.2 (Administra)-9.8 (ti)]TJ (on \(2.4\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -1.899 Td (5.13)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Seizures)Tj /T1_1 1 Tf -0.009 Tc 0.087 Tw -3.375 -1.61 Td [(Although not reported from pre-marketing controlled c)20.3 (linical trials,)37.3 ( seizures,)37.3 ( inc)20.3 (luding)-9 ( )]TJ -0.01 Tc 0.082 Tw 0 -1.07 Td [(grand mal convulsions,)37.3 ( ha)-9.6 (ve been reported during post-a)-9.6 (pproval use of )37.2 (THALOMID in)-10 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.07 Td [(c)20.3 (linical practice.)37.3 ( Because these events are reported voluntarily from a popula)-9.7 (tion of)-5 ( )]TJ -0.018 Tc 0.036 Tw 0 -1.07 Td [(unkno)-10.3 (wn size,)36.7 ( estima)-10.4 (tes of frequenc)19.6 (y cannot be made.)36.6 ( Most pa)-10.4 (tients had disorders tha)-10.3 (t)-18 ( )]TJ -0.01 Tc 0.081 Tw 0 -1.07 Td [(m)0.5 (a)0.5 (y h)0.5 (a)-9.5 (ve)0.5 ( p)0.5 (r)0.5 (ed)0.5 (i)0.5 (sp)0.5 (o)0.5 (s)0.5 (ed)0.5 ( t)0.5 (he)0.5 (m)0.5 ( t)0.5 (o s)0.5 (e)0.5 (iz)0.5 (u)0.5 (r)0.5 (e a)0.5 (c)0.5 (t)0.5 (iv)0.5 (i)0.5 (t)0.5 (y)55.4 (,)37.5 ( a)0.5 (n)0.5 (d)0.5 ( it)0.5 ( i)0.5 (s n)0.5 (ot)0.5 ( c)0.5 (u)0.5 (rr)0.5 (e)0.5 (n)0.5 (tl)0.5 (y)0.5 ( kn)0.5 (o)-9.5 (w)0.5 (n w)0.5 (h)0.5 (et)0.5 (h)0.5 (e)0.5 (r)-10 ( )]TJ -0.022 Tc 0.036 Tw 0 -1.07 Td [(THALOMID has an)-10.1 (y epileptogenic in\035uence.)36.9 ( During thera)-10 (py with )37 (THALOMID,)37 ( pa)-10.1 (tients with)-22 ( )]TJ -0.017 Tc 0.04 Tw 0 -1.07 Td [(a histor)-17.8 (y of seizures or with other risk factors for the development of seizures\ should be)-17 ( )]TJ 0.048 Tw 0 -1.07 Td [(monitored c)20.2 (losely for c)20.1 (linical changes tha)-9.8 (t could precipita)-9.8 (te acute seizure activity)55.2 (.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.899 Td (5.14)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(T)74.2 (umor L)37.2 (ysis Syndrome)]TJ /T1_1 1 Tf -0.014 Tc 0.065 Tw -3.375 -1.61 Td [(Monitor pa)-10.2 (tients a)-10.2 (t risk of tumor lysis syndrome \(e.g.,)36.7 ( pa)-10.2 (tients with high tumor burden)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(prior to trea)-9.8 (tment\) and take a)-9.8 (ppropria)-9.8 (te precautions.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.899 Td (5.15)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Contraceptive Risks)Tj /T1_1 1 Tf 0.006 Tc 0.166 Tw -3.375 -1.61 Td [(Some contraceptive methods may pose a higher risk of adverse effects or \ may)6.1 ( )]TJ 0.007 Tc 0.172 Tw 0 -1.07 Td [(be medically )0.5 (contraindica)-10.4 (ted in some )0.5 (pa)-10.4 (tients )0.5 (trea)-10.4 (ted with )37.4 (THALOMID.)36.5 ( )0.5 (Because)7.1 ( )]TJ -0.012 Tc 0.072 Tw 0 -1.07 Td [(some pa)-9.7 (tients may develop sudden,)37.3 ( severe neutropenia and/or thromboc)20.3 (ytopenia,)37.3 ( use)-12 ( )]TJ -0.015 Tc 0.061 Tw 0 -1.07 Td [(of )0.5 (an )0.5 (intrauterine )0.5 (device )0.5 (\(IUD\) )0.5 (or )0.5 (implantable )0.5 (contraception )0.5 (in )0.6 (these )0.6 (pa)-10.2 (tients )0.5 (may )0.6 (carr)-18.2 (y)-15 ( )]TJ -0.007 Tc 0.1 Tw 0 -1.07 Td [(an increased risk for infection or bleeding either a)-10.1 (t )0.5 (insertion,)36.9 ( )0.5 (removal )0.5 (or during use.)30 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.07 Td [(T)74.2 (rea)-9.8 (tment with )37.2 (THALOMID,)37.2 ( the presence of an underlying malignanc)20.1 (y)55.2 (,)37.2 ( and/or use of an)-15 ( )]TJ -0.008 Tc 0.091 Tw 0 -1.07 Td [(e)0.5 (st)0.5 (r)0.5 (og)0.5 (e)0.5 (n-)0.5 (co)0.5 (n)0.5 (ta)0.5 (i)0.5 (ni)0.5 (ng)0.5 ( c)0.5 (on)0.5 (t)0.5 (ra)0.5 (c)0.5 (ep)0.5 (t)0.5 (iv)0.5 (e)0.5 ( ca)0.5 (n)0.5 ( e)0.5 (ac)0.5 (h in)0.5 (c)0.5 (re)0.5 (a)0.5 (se)0.5 ( t)0.5 (he)0.5 ( r)0.5 (i)0.5 (sk)0.5 ( o)0.5 (f th)0.5 (r)0.5 (om)0.5 (b)0.5 (oe)0.5 (m)0.5 (bo)0.5 (l)0.5 (is)0.5 (m.)37.5 ( I)0.5 (t)-8 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.07 Td [(is not kno)-9.7 (wn if these risks of thromboembolism are additive.)37.2 ( Ho)-9.8 (wever)74.2 (,)37.2 ( they should be)-12 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(taken into considera)-9.8 (tion when choosing contraceptive methods.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.899 Td (5.16)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Hypersensitivity)Tj /T1_1 1 Tf -0.006 Tc 0.106 Tw -3.375 -1.61 Td [(Hypersensitivity)54.7 (,)36.6 ( inc)19.6 (luding angioedema and ana)-10.3 (phylactic reactions to )36.7 (THALOMID has)-6 ( )]TJ -0.004 Tc 0.112 Tw 0 -1.07 Td [(been reported.)37.3 ( Signs and symptoms ha)-9.6 (ve inc)20.3 (luded the occurrence of er)-17.6 (ythema)-9.6 (tous)-4 ( )]TJ 0.001 Tc 0.138 Tw 0 -1.07 Td [(macular rash,)37.2 ( possibly associa)-9.7 (ted with fever)74.2 (,)37.2 ( tachycardia,)37.2 ( and hypotension,)37.2 ( and if)1 ( )]TJ -0.009 Tc 0.088 Tw 0 -1.07 Td [(severe,)37.1 ( may necessita)-9.9 (te interruption of thera)-9.9 (py)55.1 (.)37.1 ( If the reaction recurs when dosing is)-9 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.07 Td [(resum)0.5 (ed,)37.4 ( )37.4 (THALOMID )0.5 (should be)0.5 ( discontinue)0.5 (d.)37.4 ( Do not)0.5 ( resume )37.4 (T)0.5 (HALOMID t)0.5 (rea)-9.6 (tme)0.5 (nt afte)0.5 (r)-16 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(angioedema and ana)-9.8 (phylaxis )]TJ /T1_2 1 Tf [([see Dosa)-9.8 (ge and )37.2 (Administra)-9.7 (ti)]TJ (on \(2.4\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -2.074 Td (6)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (ADVERSE REACTIONS)Tj /T1_1 1 Tf -0.004 Tc 0.111 Tw -3.375 -1.745 Td [(T)0.5 (h)0.5 (e)0.5 ( f)0.5 (o)0.5 (l)0.5 (l)0.5 (o)-9.5 (w)0.5 (i)0.5 (n)0.6 (g)0.5 ( c)20.5 (l)0.5 (i)0.5 (n)0.5 (i)0.5 (c)0.5 (a)0.5 (l)0.5 (l)0.6 (y)0.5 ( s)0.5 (i)0.5 (g)0.5 (n)0.5 (i)0.5 (\036)0.5 (c)0.5 (a)0.6 (n)0.5 (t)0.5 ( a)0.5 (d)0.5 (v)0.6 (e)0.5 (r)0.5 (s)0.5 (e)0.5 ( r)0.5 (e)0.6 (a)0.5 (c)0.5 (t)0.5 (i)0.5 (o)0.5 (n)0.6 (s)0.5 ( a)0.5 (r)0.5 (e)0.5 ( d)0.6 (e)0.5 (s)0.5 (c)0.5 (r)0.5 (i)0.5 (b)0.5 (e)0.5 (d)0.5 ( i)0.5 (n)0.5 ( d)0.5 (e)0.5 (t)0.5 (a)0.6 (i)0.5 (l)0.5 ( i)0.5 (n)0.5 ( o)0.6 (t)0.5 (h)0.5 (e)0.5 (r)-4 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td (labeling sections:)Tj 0.017 Tw 1.192 -1.674 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.004 Tc 0.004 Tw 1.508 0 Td [(T)74.4 (era)-9.6 (togenicity )]TJ /T1_2 1 Tf 0.112 Tw 5.442 0 Td [([see Boxed )37.2 (W)18.4 (arning,)37.4 ( )37.2 (W)18.3 (arnings and Precautions \(5.1,)37.4 ( 5.2\),)37.3 ( and)-4 ( )]TJ -0.017 Tc 0.048 Tw -5.442 -1.089 Td [(P)18.2 (a)-9.8 (tient Counseling Informa)-9.7 (tion \(17\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.539 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.005 Tc 0.119 Tw 1.508 0 Td [(V)18.5 (e)0.5 (no)0.5 (u)0.5 (s )-37.2 (a)0.5 (n)0.5 (d)0.5 ( A)0.5 (r)0.5 (t)0.5 (e)0.5 (ri)0.5 (a)0.5 (l T)0.5 (h)0.5 (r)0.5 (om)0.5 (b)0.5 (o)0.5 (e)0.5 (mb)0.5 (o)0.5 (l)0.5 (is)0.5 (m)0.5 ( )]TJ /T1_2 1 Tf 15.263 0 Td [([)0.5 (s)0.5 (ee)0.5 ( )-37.2 (B)0.5 (o)0.5 (xe)0.5 (d)0.5 ( W)18.5 (ar)0.5 (n)0.5 (in)0.5 (g)0.5 (,)37.5 ( W)18.5 (a)0.5 (r)0.5 (ni)0.5 (n)0.5 (g)0.5 (s )-37.2 (a)0.5 (n)0.5 (d)5 ( )]TJ -0.017 Tc 0.048 Tw -15.263 -1.089 Td [(Precautions \(5.3\),)37.2 ( and P)18.2 (a)-9.7 (tient Counseling Informa)-9.8 (tion \(17\)])]TJ /T1_1 1 Tf 0.017 Tw 34.493 86.406 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.004 Tc 0.112 Tw 1.508 0 Td [(Inc)0.5 (rea)0.5 (sed )0.5 (M)0.5 (ort)0.5 (alit)0.5 (y )0.5 (in )0.6 (P)18.4 (a)-9.6 (t)0.5 (ients)0.5 ( )0.5 (wit)0.5 (h )0.5 (MM )37.5 (W)0.5 (hen )0.6 (P)18.4 (embr)0.5 (oli)0.5 (zuma)0.5 (b )0.5 (Is )37.5 (A)0.5 (dded)0.5 ( )0.5 (to )0.5 (a)-3.9 ( )]TJ -0.017 Tc 0.042 Tw 0 -1.09 Td [(Thalidomide )37.4 (Analogue and )0.5 (Dexamethasone )]TJ /T1_2 1 Tf [([see )37.4 (W)18.2 (arnings )0.5 (and Precautions )0.5 (\(5.4\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td [(Dro)-9.8 (wsiness and Somnolence )]TJ /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.5\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td [(P)18.2 (eripheral Neuropa)-9.8 (thy )]TJ /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.6\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td [(Dizziness and Orthosta)-9.8 (tic Hypotension )]TJ /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.7\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 1.508 0 Td (Neutropenia )Tj /T1_2 1 Tf 0.048 Tw 4.561 0 Td [([see )37.2 (W)18.2 (arnings and Precautions \(5.8\)])]TJ /T1_1 1 Tf 0.017 Tw -6.069 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 1.508 0 Td [(Thromboc)20.2 (ytopenia )]TJ /T1_2 1 Tf 0.048 Tw 6.823 0 Td [([see )37.3 (W)18.2 (arnings and Precautions \(5.9\)])]TJ /T1_1 1 Tf 0.017 Tw -8.331 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td [(Increased HIV )37.2 (Viral Load )]TJ /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.10\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 1.508 0 Td [(Brad)-9.8 (ycardia )]TJ /T1_2 1 Tf 0.048 Tw 4.496 0 Td [([see )37.3 (W)18.2 (arnings and Precautions \(5.11\)])]TJ /T1_1 1 Tf 0.017 Tw -6.004 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td (Severe Cutaneous Reactions )Tj /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.12\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 1.508 0 Td (Seizures )Tj /T1_2 1 Tf 0.048 Tw 3.28 0 Td [([see )37.3 (W)18.2 (arnings and Precautions \(5.13\)])]TJ /T1_1 1 Tf 0.017 Tw -4.788 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.508 0 Td [(T)74.2 (umor L)37.2 (ysis Syndrome )]TJ /T1_2 1 Tf [([see )37.2 (W)18.2 (arnings and Precautions \(5.14\)])]TJ /T1_1 1 Tf 0.017 Tw -1.508 -1.54 Td (\225)Tj /Span<>> BDC ( )Tj EMC 1.508 0 Td (Hypersensitivity )Tj /T1_2 1 Tf 0.048 Tw 5.804 0 Td [([see )37.3 (W)18.2 (arnings and Precautions \(5.16\)])]TJ /T1_0 1 Tf 0.017 Tw -8.504 -1.765 Td (6.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Clinical T)74.2 (rials Experience)]TJ /T1_1 1 Tf -0.014 Tc 0.066 Tw -3.375 -1.612 Td [(Because c)19.6 (linical trials are conducted under widely var)-18.3 (ying conditions,)36.6 ( adverse reaction)-14 ( )]TJ -0.017 Tc 0.045 Tw 0 -1.072 Td [(ra)-9.8 (tes obser)-17.8 (ved in the c)20.2 (linical trials of a drug cannot be directly compared to ra)-9.8 (tes in the)-17 ( )]TJ 0.048 Tw 0 -1.072 Td [(c)20.2 (linical trials of another drug and may not re\035ect the ra)-9.7 (tes obser)-17.8 (ved in practice.)]TJ 0 -1.792 Td [(Most pa)-9.8 (tients taking )37.2 (THALOMID can be expected to experience adverse reactions.)]TJ /T1_0 1 Tf 0 -2.013 Td [(Adverse Reactions in Multiple Myeloma Controlled Clinical T)74.1 (rials)]TJ /T1_1 1 Tf -0.004 Tc 0.115 Tw 0 -1.567 Td [(The safety analyses were conducted in two controlled c)19.8 (linical studies \(Stud)-10.2 (y 1 and)-3.9 ( )]TJ -0.012 Tc 0.072 Tw 0 -1.072 Td [(Stud)-9.7 (y 2\).)37.3 ( )36.9 (The safety analysis in Stud)-9.7 (y 1 was conducted on 204 pa)-9.7 (tients who received)-12 ( )]TJ 0.006 Tc 0.162 Tw 0 -1.072 Td [(trea)-9.6 (tment.)37.4 ( )36.9 (T)74.3 (able 1 lists the most common adverse reactions \(\037 10%\).)37.3 ( )37 (The most)6 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.072 Td [(frequently reported adverse reactions were fa)-9.9 (tigue,)37.1 ( hypocalcemia,)37.2 ( edema,)37.1 ( constipa)-9.9 (tion,)22 ( )]TJ 0.01 Tc 0.186 Tw 0 -1.072 Td [(sensor)-18.3 (y neuropa)-10.4 (thy)54.6 (,)36.6 ( d)-10.4 (yspnea,)36.6 ( musc)19.6 (le weakness,)36.6 ( leukopenia,)36.6 ( neutropenia,)36.6 ( rash/)]TJ -0.015 Tc 0.06 Tw 0 -1.072 Td [(desquama)-9.7 (tion,)37.3 ( confusion,)37.4 ( anorexia,)37.3 ( nausea,)37.3 ( anxiety/a)-9.7 (gita)-9.7 (tion,)37.3 ( tremor)74.3 (,)37.4 ( fever)74.3 (,)37.3 ( weight loss,)22 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.072 Td [(thrombosis/embolism,)37.2 ( neuropa)-9.8 (thy-motor)74.2 (,)37.2 ( weight gain,)37.2 ( dizziness,)37.2 ( and dr)-17.7 (y skin.)]TJ 0.003 Tc 0.148 Tw 0 -1.792 Td [(T)74.2 (wenty-three percent of pa)-9.8 (tients \(47/204\) discontinued due to adverse reactions;)3 ( )]TJ -0.005 Tc 0.107 Tw 0 -1.072 Td [(30% \(31/102\) from the )36.9 (THALOMID/dexamethasone arm and 16% \(16/102\) from the)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.072 Td (dexamethasone alone arm.)Tj ET /GS2 gs q 1 0 0 1 429.4801 378.9855 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 466.11 378.9855 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 378.9855 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 378.9855 cm 0 0 m 36.63 0 l S Q 0.5 w q 1 0 0 1 502.7401 357.8236 cm 0 0 m 0 20.662 l S Q 1 w q 1 0 0 1 324.0001 378.9855 cm 0 0 m 105.48 0 l S Q 0.5 w q 1 0 0 1 429.4801 357.8236 cm 0 0 m 0 20.662 l S Q q 1 0 0 1 324.0001 336.1617 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 324.0001 325.1597 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 325.1597 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 325.1597 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 314.4078 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 314.4078 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 314.4078 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 303.6559 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 303.6559 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 303.6559 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 292.904 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 292.904 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 292.904 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 282.1521 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 282.1521 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 282.1521 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 271.4002 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 271.4002 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 271.4002 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 260.6483 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 260.6483 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 260.6483 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 249.8963 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 249.8963 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 249.8963 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 239.1444 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 239.1444 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 239.1444 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 228.3925 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 228.3925 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 228.3925 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 217.6406 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 217.6406 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 217.6406 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 163.881 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 163.881 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 163.881 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 142.3772 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 142.3772 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 142.3772 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 131.6253 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 131.6253 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 131.6253 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 77.8657 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 77.8657 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 77.8657 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 206.8887 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 206.8887 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 206.8887 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 196.1368 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 196.1368 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 196.1368 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 185.3849 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 185.3849 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 185.3849 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 174.6329 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 174.6329 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 174.6329 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 153.1291 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 153.1291 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 153.1291 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 120.8734 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 120.8734 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 120.8734 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 110.1215 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 110.1215 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 110.1215 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 99.3695 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 99.3695 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 99.3695 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 88.6176 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 88.6176 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 88.6176 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 324.0001 67.1138 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 466.11 67.1138 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 67.1138 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.2301 357.5736 cm 0 0 m 36.88 0 l S Q q 1 0 0 1 429.4801 336.4117 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 466.11 357.5736 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 466.11 336.4117 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 502.7401 357.5736 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 336.4117 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 539.3701 357.5736 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 336.4117 cm 0 0 m 0 20.912 l S Q q 1 0 0 1 429.4801 336.1617 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 466.11 336.1617 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 336.1617 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 336.1617 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 325.4097 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 466.11 325.4097 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 429.4801 325.1597 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 314.6578 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 314.6578 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 314.4078 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 303.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 303.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 303.6559 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 293.154 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 293.154 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 292.904 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 282.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 282.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 282.1521 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 271.6502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 271.6502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 271.4002 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 260.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 260.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 260.6483 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 250.1463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 250.1463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 249.8963 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 239.3944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 239.3944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 239.1444 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 228.6425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 228.6425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 228.3925 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 217.8906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 217.8906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 217.6406 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 207.1387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 207.1387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 206.8887 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 196.3868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 196.3868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 196.1368 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 185.6349 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 185.6349 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 185.3849 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 174.8829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 174.8829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 174.6329 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 164.131 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 164.131 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 163.881 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 153.3791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 153.3791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 153.1291 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 142.6272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 142.6272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 142.3772 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 131.8753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 131.8753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 131.6253 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 121.1234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 121.1234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 120.8734 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 110.3715 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 110.3715 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 110.1215 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 99.6195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 99.6195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 99.3695 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 88.8676 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 88.8676 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 88.6176 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 78.1157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 78.1157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 77.8657 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 67.3638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 67.3638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 429.4801 67.1138 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 429.4801 56.6119 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 466.11 56.6119 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 325.4097 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 539.3701 325.4097 cm 0 0 m 0 10.502 l S Q q 1 0 0 1 502.7401 325.1597 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 314.6578 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 314.6578 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 314.4078 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 303.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 303.9059 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 303.6559 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 293.154 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 293.154 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 292.904 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 282.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 282.4021 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 282.1521 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 271.6502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 271.6502 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 271.4002 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 260.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 260.8983 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 260.6483 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 250.1463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 250.1463 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 249.8963 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 239.3944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 239.3944 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 239.1444 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 228.6425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 228.6425 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 228.3925 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 217.8906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 217.8906 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 217.6406 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 207.1387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 207.1387 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 206.8887 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 196.3868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 196.3868 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 196.1368 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 185.6349 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 185.6349 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 185.3849 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 174.8829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 174.8829 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 174.6329 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 164.131 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 164.131 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 163.881 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 153.3791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 153.3791 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 153.1291 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 142.6272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 142.6272 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 142.3772 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 131.8753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 131.8753 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 131.6253 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 121.1234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 121.1234 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 120.8734 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 110.3715 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 110.3715 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 110.1215 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 99.6195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 99.6195 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 99.3695 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 88.8676 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 88.8676 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 88.6176 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 78.1157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 78.1157 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 77.8657 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 67.3638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 67.3638 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 502.7401 67.1138 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 56.6119 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 539.3701 56.6119 cm 0 0 m 0 10.252 l S Q q 1 0 0 1 324.0001 56.3619 cm 0 0 m 105.48 0 l S Q q 1 0 0 1 429.4801 56.3619 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 466.11 56.3619 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 502.7401 56.3619 cm 0 0 m 36.63 0 l S Q q 1 0 0 1 539.3701 56.3619 cm 0 0 m 36.63 0 l S Q BT /GS1 gs /T1_0 1 Tf -0.01 Tc 0.085 Tw 8 0 0 8 324.0001 391.0855 Tm [(T)81.2 (a)7.2 (b)7.2 (l)7.2 (e)7.2 ( )44.3 (1)7.2 (:)]TJ /Span<>> BDC 2.96 0 Td ( )Tj EMC 2.04 0 Td [(Adverse Reactions Reported in \03610% of P)23.9 (atients in the THALOMID/)]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(De)10.2 (xamethasone Arm \(Study 1 - Safety P)24.2 (opulation; N=204\))]TJ -0.012 Tc 7.6 0 0 8 324.0001 348.2617 Tm (Body System)Tj 0 Tc 0 Tw 7.6 0 0 8 362.5314 348.2617 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 324.0001 339.7617 Tm (Adverse Reaction)Tj 16.382 3.739 Td [(Thal + De)10.3 (x*)]TJ 0 Tc 0 Tw 7.6 0 0 8 483.719 369.6736 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 454.2057 361.1736 Tm (\(N=102\))Tj 0.048 Tw 9.074 1.062 Td [(De)10.2 (x Alone*)]TJ 0 Tc 0 Tw 7.6 0 0 8 555.8204 369.6736 Tm ( )Tj -0.012 Tc 0.012 Tw 7.6 0 0 8 527.5906 361.1736 Tm (\(N=102\))Tj 0.048 Tw -12.495 -1.614 Td (All Grades)Tj 0 Tc 0 Tw 7.6 0 0 8 462.9613 348.2617 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 439.7802 339.7617 Tm (n \(%\))Tj 3.967 1.062 Td (Grade 3/4)Tj 0 Tc 0 Tw 7.6 0 0 8 498.9233 348.2617 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 476.4102 339.7617 Tm (n \(%\))Tj 3.879 1.062 Td (All Grades)Tj 0 Tc 0 Tw 7.6 0 0 8 536.2213 348.2617 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 513.0402 339.7617 Tm (n \(%\))Tj 3.983 1.062 Td (Grade 3/4)Tj 0 Tc 0 Tw 7.6 0 0 8 572.3083 348.2617 Tm ( )Tj -0.012 Tc 0.048 Tw 7.6 0 0 8 549.7952 339.7617 Tm (n \(%\))Tj 0.364 Tw /Span<>> BDC -29.71 -1.51 Td ( )Tj EMC [(Metabolic/Laborator)-17.7 (y)]TJ /T1_1 1 Tf 0.048 Tw 14.98 0 Td (97 \(95\))Tj 4.82 0 Td (33 \(32\))Tj 4.82 0 Td (96 \(94\))Tj 4.836 0 Td (30 \(29\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC (Hypocalcemia)Tj 0.048 Tw 14.98 0 Td (73 \(72\))Tj 4.82 0 Td (11 \(11\))Tj 4.82 0 Td (60 \(59\))Tj 5.304 0 Td (5 \(5\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Neurolog)-9.8 (y)]TJ /T1_1 1 Tf 0.048 Tw 14.98 0 Td (92 \(90\))Tj 4.82 0 Td (30 \(29\))Tj 4.82 0 Td (76 \(74\))Tj 4.836 0 Td (18 \(18\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(Neuropa)-9.8 (thy-sensor)-17.8 (y)]TJ 0.048 Tw 14.98 0 Td (55 \(54\))Tj 5.288 0 Td (4 \(4\))Tj 4.352 0 Td (28 \(28\))Tj 5.304 0 Td (1 \(1\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Confusion)Tj 0.048 Tw 14.98 0 Td (29 \(28\))Tj 5.288 0 Td (9 \(9\))Tj 4.352 0 Td (12 \(12\))Tj 5.304 0 Td (3 \(3\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Anxiety/a)-9.8 (gita)-9.8 (tion)]TJ 0.048 Tw 14.98 0 Td (26 \(26\))Tj 5.288 0 Td (1 \(1\))Tj 4.352 0 Td (14 \(14\))Tj 5.304 0 Td (3 \(3\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(T)74.2 (remor)]TJ 0.048 Tw 14.98 0 Td (26 \(26\))Tj 5.288 0 Td (1 \(1\))Tj 4.82 0 Td (6 \(6\))Tj 4.836 0 Td (0 \(0\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Neuropa)-9.8 (thy-motor)]TJ 0.048 Tw 14.98 0 Td (22 \(22\))Tj 5.288 0 Td (8 \(8\))Tj 4.352 0 Td (16 \(16\))Tj 5.304 0 Td (5 \(5\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Dizziness/lightheadedness)Tj 0.048 Tw 14.98 0 Td (20 \(20\))Tj 5.288 0 Td (1 \(1\))Tj 4.352 0 Td (14 \(14\))Tj 5.304 0 Td (0 \(0\))Tj /Span<>> BDC -29.924 -1.344 Td [( )-316.1 ( )]TJ EMC 1.184 0 Td (Depressed level of consciousness)Tj 13.796 0 Td (16 \(16\))Tj 5.288 0 Td (3 \(3\))Tj 4.82 0 Td (3 \(3\))Tj 4.836 0 Td (3 \(3\))Tj /T1_0 1 Tf /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC 0.592 0 Td (Constitutional Symptoms)Tj /T1_1 1 Tf 14.388 0 Td (91 \(89\))Tj 4.82 0 Td (19 \(19\))Tj 4.82 0 Td (84 \(82\))Tj 4.836 0 Td (16 \(16\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(F)20.2 (a)-9.8 (tigue)]TJ 0.048 Tw 14.98 0 Td (81 \(79\))Tj 4.82 0 Td (17 \(17\))Tj 4.82 0 Td (72 \(71\))Tj 4.836 0 Td (13 \(13\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(F)24.2 (ever)]TJ 0.048 Tw 14.98 0 Td (24 \(24\))Tj 5.288 0 Td (1 \(1\))Tj 4.352 0 Td (20 \(20\))Tj 5.304 0 Td (3 \(3\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(W)18.2 (eight )316.2 (loss)]TJ 0.048 Tw 14.98 0 Td (23 \(23\))Tj 5.288 0 Td (1 \(1\))Tj 4.352 0 Td (21 \(21\))Tj 5.304 0 Td (2 \(2\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(W)18.2 (eight )316.2 (gain)]TJ 0.048 Tw 14.98 0 Td (22 \(22\))Tj 5.288 0 Td (1 \(1\))Tj 4.352 0 Td (13 \(13\))Tj 5.304 0 Td (0 \(0\))Tj /T1_0 1 Tf /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC 0.592 0 Td (Blood/Bone Marrow)Tj /T1_1 1 Tf 14.388 0 Td (88 \(86\))Tj 4.82 0 Td (29 \(29\))Tj 4.82 0 Td (96 \(94\))Tj 4.836 0 Td (19 \(19\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC [(Leukoc)20.2 (ytes )316.2 (\(decreased\))]TJ 0.048 Tw 14.98 0 Td (36 \(35\))Tj 5.288 0 Td (6 \(6\))Tj 4.352 0 Td (30 \(29\))Tj 5.304 0 Td (3 \(3\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Neutrophils )316.3 (\(decreased\))]TJ 0.048 Tw 14.98 0 Td (32 \(31\))Tj 4.82 0 Td (10 \(10\))Tj 4.82 0 Td (24 \(24\))Tj 4.836 0 Td (10 \(10\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC (Gastrointestinal)Tj /T1_1 1 Tf 0.048 Tw 14.98 0 Td (83 \(81\))Tj 4.82 0 Td (22 \(22\))Tj 4.82 0 Td (70 \(69\))Tj 5.304 0 Td (8 \(8\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Constipa)-9.8 (tion)]TJ 0.048 Tw 14.98 0 Td (56 \(55\))Tj 5.288 0 Td (8 \(8\))Tj 4.352 0 Td (29 \(28\))Tj 5.304 0 Td (1 \(1\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Anorexia)Tj 0.048 Tw 14.98 0 Td (29 \(28\))Tj 5.288 0 Td (4 \(4\))Tj 4.352 0 Td (25 \(24\))Tj 5.304 0 Td (2 \(2\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Nausea)Tj 0.048 Tw 14.98 0 Td (29 \(28\))Tj 5.288 0 Td (5 \(5\))Tj 4.352 0 Td (23 \(22\))Tj 5.304 0 Td (1 \(1\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Mouth )316.2 (dr)-17.8 (yness)]TJ 0.048 Tw 14.98 0 Td (12 \(12\))Tj 5.288 0 Td (1 \(1\))Tj 4.82 0 Td (6 \(6\))Tj 4.836 0 Td (0 \(0\))Tj /T1_0 1 Tf 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC [(Cardio)-9.8 (v)16.2 (ascular)]TJ /T1_1 1 Tf 0.048 Tw 14.98 0 Td (70 \(69\))Tj 4.82 0 Td (37 \(36\))Tj 4.82 0 Td (60 \(59\))Tj 4.836 0 Td (21 \(21\))Tj 0.364 Tw /Span<>> BDC -29.456 -1.344 Td ( )Tj EMC (Edema)Tj 0.048 Tw 14.98 0 Td (58 \(56\))Tj 5.288 0 Td (6 \(6\))Tj 4.352 0 Td (47 \(46\))Tj 5.304 0 Td (4 \(4\))Tj 0.364 Tw /Span<>> BDC -29.924 -1.344 Td ( )Tj EMC (Thrombosis/embolism)Tj 0.048 Tw 14.98 0 Td (23 \(22\))Tj 4.82 0 Td (21 \(21\))Tj 5.288 0 Td (5 \(5\))Tj 4.836 0 Td (5 \(5\))Tj /T1_2 1 Tf 0 Tc 0 Tw 8 0 0 8 543.7445 47.88 Tm (\()Tj -0.017 Tc 0.017 Tw 0.224 0 Td (Continued\))Tj ET 1 w 4 M q 1 0 0 1 319.5 41.6519 cm 0 0 m S Q endstream endobj 108 0 obj <>stream q /GS0 gs 0 TL/Fm0 Do Q 0.5 w /GS1 gs q 1 0 0 1 36 433.8436 cm 0 0 m 96.93 0 l S Q q 1 0 0 1 36 303.0157 cm 0 0 m 17.073 0 l S Q q 1 0 0 1 36 242.7882 cm 0 0 m 43.402 0 l S Q BT /T1_0 1 Tf -0.017 Tc 0.045 Tw 8 0 0 8 36 727.248 Tm [(Precautions \(5.1\) and Use in Speci\037c P)18.2 (opula)-9.7 (tions \(8.1\)])]TJ /T1_1 1 Tf [(.)37.2 ( )37.3 (THALOMID is a po)-9.8 (werful human)-17 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.068 Td [(tera)-9.8 (togen,)37.1 ( inducing a high frequenc)20.1 (y of severe and life-threa)-9.8 (tening birth defects,)37.1 ( even)-12 ( )]TJ -0.005 Tc 0.109 Tw 0 -1.068 Td [(after )0.5 (a )0.5 (single )0.5 (dose )]TJ /T1_0 1 Tf 0.072 Tw 7.381 0 Td [([see )-36.5 (Boxed )0.6 (W)18 (arning])]TJ /T1_1 1 Tf 0.109 Tw [(.)37 ( )0.5 (Mortality )0.5 (a)-9.9 (t )0.5 (or )0.5 (shortly )0.5 (after )0.5 (birth )0.5 (has )0.6 (been)-5 ( )]TJ -0.016 Tc 0.06 Tw -7.381 -1.068 Td [(reported in about 40% of infants.)36.8 ( If this drug is used during pregnanc)19.7 (y)54.8 (,)36.8 ( or if the pa)-10.2 (tient)-16 ( )]TJ -0.017 Tc 0.036 Tw 0 -1.068 Td [(becomes pregnant while taking this drug,)37.3 ( the pa)-9.7 (tient should be a)-9.7 (pprised of the potential)-17 ( )]TJ -0.006 Tc 0.101 Tw 0 -1.068 Td [(r)0.5 (i)0.6 (s)0.5 (k)0.5 ( t)0.6 (o)0.5 ( a)0.5 ( f)0.6 (e)0.5 (t)0.5 (u)0.6 (s)0.5 (.)37.5 ( I)0.5 (f)0.6 ( p)0.5 (r)0.5 (e)0.6 (g)0.5 (n)0.5 (a)0.6 (n)0.5 (c)20.5 (y)0.5 ( o)0.6 (c)0.5 (c)0.5 (u)0.5 (r)0.5 (s)0.6 ( d)0.5 (u)0.5 (r)0.6 (i)0.5 (n)0.5 (g)0.5 ( )37.1 (T)0.5 (H)0.6 (A)0.5 (L)0.5 (O)0.5 (M)0.6 (I)0.5 (D)0.5 ( t)0.6 (r)0.5 (e)0.5 (a)-9.4 (t)0.5 (m)0.5 (e)0.6 (n)0.5 (t)0.5 (,)37.5 ( t)0.6 (h)0.5 (e)0.5 ( d)0.6 (r)0.5 (u)0.5 (g)0.5 ( s)0.6 (h)0.5 (o)0.5 (u)0.6 (l)0.5 (d)0.5 ( b)0.5 (e)-6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(discontinued immedia)-9.8 (tely)55.2 (.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.897 Td (4.2)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Hypersensitivity)Tj /T1_1 1 Tf 0.059 Tw -3.375 -1.608 Td [(THALOMID is contraindica)-9.8 (ted in pa)-9.8 (tients who ha)-9.7 (ve demonstra)-9.7 (ted hypersensitivity to the)-17 ( )]TJ 0.048 Tw 0 -1.068 Td (drug or its components )Tj /T1_0 1 Tf [([see )37.2 (W)18.2 (arnings and Precaution)]TJ (s \(5.16\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_2 1 Tf -0.017 Tc 0.017 Tw 0 -2.072 Td (5)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(W)18.2 (ARNINGS AND PREC)18.2 (AUTIONS)]TJ 0.017 Tw -3.375 -1.762 Td (5.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Embr)-17.7 (yo-F)20.2 (etal T)74.2 (oxicity)]TJ /T1_1 1 Tf -0.015 Tc 0.06 Tw -3.375 -1.608 Td [(THALOMID is a po)-9.8 (werful human tera)-9.8 (togen tha)-9.8 (t induces a high frequenc)20.2 (y of severe and)-15 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.068 Td [(life-threa)-9.8 (tening birth defects,)37.1 ( even after a single dose.)37.1 ( Mortality a)-9.9 (t or shortly after birth)-14.1 ( )]TJ -0.007 Tc 0.096 Tw 0 -1.068 Td [(h)0.5 (as be)0.5 (en)0.5 ( re)0.5 (po)0.5 (rt)0.5 (ed)0.5 ( i)0.5 (n abo)0.5 (ut)0.5 ( 4)0.5 (0%)0.5 ( o)0.5 (f i)0.5 (nf)0.5 (an)0.5 (ts)0.5 (.)37.4 ( )36.6 (W)0.5 (he)0.5 (n the)0.5 (re)0.5 ( i)0.5 (s no)0.5 ( sa)-9.5 (ti)0.5 (sf)0.5 (ac)0.5 (to)0.5 (r)-17.6 (y)0.5 ( a)0.5 (lte)0.5 (rn)0.5 (a)-9.6 (t)0.5 (iv)0.5 (e)-7 ( )]TJ -0.009 Tc 0.086 Tw 0 -1.068 Td [(t)0.5 (r)0.5 (e)0.5 (a)-9.5 (t)0.5 (m)0.5 (e)0.5 (n)0.5 (t)0.5 (,)37.5 ( f)0.5 (e)0.5 (m)0.5 (a)0.5 (l)0.5 (e)0.5 (s)0.5 ( o)0.5 (f)0.5 ( r)0.5 (e)0.5 (p)0.5 (r)0.5 (o)0.5 (d)0.5 (u)0.5 (c)0.5 (t)0.5 (i)0.5 (v)0.5 (e)0.5 ( p)0.5 (o)0.5 (t)0.5 (e)0.5 (n)0.5 (t)0.5 (i)0.5 (a)0.5 (l)0.5 ( m)0.5 (a)0.5 (y)0.5 ( b)0.5 (e)0.5 ( t)0.6 (re)0.5 (a)-9.4 (t)0.5 (e)0.5 (d w)0.5 (i)0.5 (t)0.5 (h)0.5 ( )36.9 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.5 (I)0.5 (D)0.5 ( p)0.5 (r)0.5 (o)0.5 (v)0.5 (i)0.5 (d)0.5 (e)0.5 (d)-9 ( )]TJ -0.017 Tc 0.043 Tw 0 -1.068 Td [(adequa)-9.7 (te precautions are taken to a)-9.8 (void pregnanc)20.2 (y)55.2 (.)37.2 ( )36.8 (THALOMID is only a)-9.8 (vailable through)-17 ( )]TJ 0.048 Tw 0 -1.068 Td [(the )37.2 (THALOMID REMS program )]TJ /T1_0 1 Tf [([see )37.2 (W)18.2 (arnings and Precautio)]TJ (ns \(5.2\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.002 Tc 0.125 Tw 0 -1.743 Td [(Oral )0.5 (ingestion )0.5 (is )0.6 (the )0.5 (only )0.5 (type )0.6 (of )0.6 (ma)-10.1 (ternal )37.5 (THALOMID )0.6 (exposure )0.5 (kno)-10.1 (wn )0.6 (to )0.5 (result )0.6 (in)-2 ( )]TJ 0.005 Tc 0.157 Tw 0 -1.068 Td [(dr)0.5 (ug-a)0.5 (sso)0.5 (cia)-9.5 (ted)0.5 ( )0.5 (bir)0.5 (th )0.5 (d)0.5 (ef)0.5 (ects)0.5 (.)37.4 ( )37.5 (The)0.5 (re)0.5 ( )0.5 (are)0.5 ( )0.5 (no)0.5 ( )0.5 (spe)0.5 (cif)0.5 (ic )0.5 (d)0.5 (a)-9.6 (ta)0.5 ( )0.5 (a)-9.6 (v)0.5 (ail)0.5 (abl)0.5 (e )0.5 (re)0.5 (gar)0.5 (din)0.5 (g )0.5 (th)0.5 (e)5 ( )]TJ -0.017 Tc 0.037 Tw 0 -1.068 Td [(reproductive risks of cutaneous absorption or inhala)-9.8 (tion of )36.9 (THALOMID; ho)-9.8 (wever)74.2 (,)37.3 ( females)-17 ( )]TJ -0.004 Tc 0.114 Tw 0 -1.068 Td [(of reproductive potential should a)-10 (void contact with )36.8 (THALOMID Ca)-10 (psules.)37 ( )36.8 (THALOMID)-4 ( )]TJ 0 Tc 0.137 Tw 0 -1.068 Td [(Ca)-10.4 (psules should be stored in )0.5 (blister packs until ingestion.)36.6 ( If there is contact with )]TJ -0.006 Tc 0.102 Tw 0 -1.068 Td [(non-intact )37.1 (THALOMID ca)-9.7 (psules or the po)-9.7 (wder contents,)37.4 ( the exposed area should be)-6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(washed with soa)-9.7 (p and wa)-9.7 (ter)74.2 (.)]TJ -0.007 Tc 0.099 Tw 0 -1.743 Td [(If healthcare providers or other care givers are exposed to bod)-10.1 (y \035uids from pa)-10.1 (tients)-7 ( )]TJ 0.007 Tc 0.168 Tw 0 -1.068 Td [(receiving )36.7 (THALOMID,)37.2 ( the exposed area should be washed with soa)-9.9 (p and wa)-9.9 (ter)74.2 (.)44 ( )]TJ 0 Tc 0.134 Tw 0 -1.068 Td [(A)-10.1 (ppropria)-10.1 (te precautions should be utilized,)36.9 ( such as wearing gloves to prevent the )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(potential cutaneous exposure to )37.1 (THALOMID.)]TJ 0 -1.694 Td [(F)24.2 (emales of Reproductive P)18.2 (otential)]TJ -0.007 Tc 0.102 Tw 0 -1.563 Td [(F)23.6 (emales of reproductive potential must a)-10.4 (void pregnanc)19.5 (y for a)-10.5 (t least 4 weeks before)-6.9 ( )]TJ -0.014 Tc 0.062 Tw 0 -1.068 Td [(beginning )36.8 (THALOMID thera)-9.7 (py)55.3 (,)37.3 ( during thera)-9.7 (py)55.3 (,)37.3 ( during dose interruptions and for a)-9.7 (t least)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(4 weeks after completing thera)-9.8 (py)55.2 (.)]TJ 0.012 Tc 0.196 Tw 0 -1.743 Td [(F)23.6 (emales must commit either to abstain continuously from heterosexual sexu\ al)12 ( )]TJ -0.006 Tc 0.106 Tw 0 -1.068 Td [(intercourse or to use two methods of reliable birth control,)36.7 ( beginning 4 weeks prior)-6 ( )]TJ 0.102 Tw 0 -1.068 Td [(to)0.5 ( )0.5 (ini)0.5 (tia)-9.5 (ting)0.5 ( )0.5 (tre)0.5 (a)-9.6 (tm)0.5 (ent)0.5 ( )0.5 (wit)0.5 (h )37.5 (THA)0.5 (LOMI)0.5 (D,)37.4 ( )0.5 (du)0.5 (ring )0.6 (the)0.5 (ra)-9.6 (p)0.5 (y)55.4 (,)37.4 ( )0.5 (du)0.5 (ring)0.5 ( )0.5 (dose)0.5 ( )0.5 (int)0.5 (err)0.5 (upt)0.5 (ions)0.5 ( )0.5 (and)-6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(continuing for 4 weeks follo)-9.8 (wing discontinua)-9.8 (tion of )37.2 (THALOMID thera)-9.7 (py)55.2 (.)]TJ -0.014 Tc 0.062 Tw 0 -1.743 Td [(T)74.4 (wo nega)-9.5 (tive pregnanc)20.4 (y tests must be obtained prior to initia)-9.6 (ting thera)-9.6 (py)55.4 (.)37.4 ( )37.4 (The)0.5 ( \036rst test)-14 ( )]TJ -0.009 Tc 0.088 Tw 0 -1.068 Td [(should be performed within 10-14 days and the second test within 24 hour\ s prior to)-9 ( )]TJ -0.008 Tc 0.091 Tw 0 -1.068 Td [(pr)0.5 (e)0.5 (scr)0.5 (ib)0.5 (in)0.5 (g )36.6 (T)0.5 (HA)0.5 (LO)0.5 (MI)0.5 (D t)0.5 (he)0.5 (ra)-9.5 (py)0.5 ( a)0.5 (nd th)0.5 (en)0.5 ( we)0.5 (e)0.5 (kl)0.5 (y d)0.5 (ur)0.5 (in)0.5 (g t)0.5 (he)0.5 ( \036)0.5 (rs)0.5 (t m)0.5 (o)0.5 (nt)0.5 (h,)37.4 ( the)0.5 (n mo)0.5 (nt)0.5 (hl)0.5 (y)-8 ( )]TJ -0.01 Tc 0.083 Tw 0 -1.068 Td [(thereafter in females with regular menstrual c)20.2 (yc)20.1 (les or ever)-17.8 (y 2 weeks in females with)-10 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(irregular menstrual c)20.2 (yc)20.2 (les )]TJ /T1_0 1 Tf [([see Use in Speci\037c P)18.2 (opula)-9.8 (tio)]TJ (ns \(8.3\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw 0 -1.694 Td (Males)Tj -0.014 Tc 0.065 Tw 0 -1.563 Td [(Thalidomide is present in the semen of pa)-10.1 (tients receiving )37 (THALOMID.)36.8 ( )36.9 (Therefore,)36.8 ( males)-14 ( )]TJ -0.017 Tc 0.046 Tw 0 -1.068 Td [(must al)-9.7 (ways use a la)-9.8 (tex or synthetic condom during an)-9.8 (y sexual contact with females of)-17 ( )]TJ 0.052 Tw 0 -1.068 Td [(reproductive potential while taking )36.6 (THALOMID and for up to 4 weeks after discontinuing)-17 ( )]TJ -0.013 Tc 0.069 Tw 0 -1.068 Td [(THALOMID,)37 ( even if they ha)-10 (ve undergone a successful vasectomy)55 (.)36.9 ( Male pa)-10 (tients taking)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(THALOMID must not dona)-9.8 (te sperm )]TJ /T1_0 1 Tf [([see Use in Speci\037c P)18.3 (opula)-9.8 (tio)]TJ (ns \(8.3\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.048 Tw 0 -1.694 Td [(Blood Dona)-9.8 (tion)]TJ -0.001 Tc 0.127 Tw 0 -1.563 Td [(P)18.4 (a)-9.6 (tie)0.5 (nts must )0.5 (not )0.5 (dona)-9.6 (te )0.5 (blood )0.5 (during tre)0.5 (a)-9.6 (tment )0.5 (with )37.4 (THAL)0.5 (OMID and )0.5 (for )0.5 (4 week)0.5 (s)-1.1 ( )]TJ -0.011 Tc 0.08 Tw 0 -1.068 Td [(follo)-10.2 (wing discontinua)-10.2 (tion of the drug because the blood might be given to a pregnant)-11 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(female pa)-9.8 (tient whose fetus must not be exposed to )37.2 (THALOMID.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.762 Td (5.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (THALOMID REMS Program)Tj /T1_1 1 Tf -0.008 Tc 0.094 Tw -3.375 -1.608 Td [(Because of the embr)-18 (yo-fetal risk )]TJ /T1_0 1 Tf [([see )36.6 (W)17.9 (arnings and Precautions \(5.1\)])]TJ /T1_1 1 Tf 0.057 Tw [(,)36.9 ( THALOMID )-37.3 (is)-8 ( )]TJ -0.002 Tc 0.123 Tw 0 -1.068 Td [(a)-9.8 (vailable only through a restricted program under a Risk Evalua)-9.8 (tion and Mitiga)-9.8 (tion)-2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.068 Td [(Stra)-9.8 (teg)-9.8 (y \(REMS\),)37.2 ( the\034)]TJ /T1_2 1 Tf 7.631 0 Td (THALOMID REMS)Tj /T1_1 1 Tf -0.198 Tw /Span<>> BDC ( )Tj EMC 6.568 0 Td [( )-245.8 (program.)]TJ 0.048 Tw -14.198 -1.743 Td (Required components of the\034)Tj /T1_2 1 Tf 10.387 0 Td (THALOMID REMS)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.568 0 Td [( program inc)20.2 (lude the follo)-9.8 (wing:)]TJ 0.017 Tw -15.763 -1.627 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.011 Tc 0.081 Tw 1.508 0 Td (Prescribers must be certi\036ed with the\034)Tj /T1_2 1 Tf 14.178 0 Td (THALOMID REMS)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.692 0 Td [( program by enrolling)-11 ( )]TJ -0.017 Tc 0.048 Tw -20.87 -1.087 Td (and complying with the REMS requirements.)Tj 0.017 Tw -1.508 -1.537 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.006 Tc 0.102 Tw 1.508 0 Td [(P)18.4 (a)-9.6 (tients must sign a P)18.4 (a)-9.6 (tient-Physician )37.3 (Agreement F)20.4 (orm and comply with the)-6 ( )]TJ -0.014 Tc 0.066 Tw 0 -1.087 Td [(REMS requirements.)36.6 ( In particular)73.5 (,)36.6 ( female pa)-10.4 (tients of reproductive potential who)-14 ( )]TJ -0.005 Tc 0.11 Tw 0 -1.087 Td [(are not pregnant must comply with the pregnanc)19.9 (y testing and contraception)-5 ( )]TJ -0.02 Tc 0.02 Tw 0 -1.087 Td (requirements )Tj /T1_0 1 Tf 0.036 Tw 4.92 0 Td [([see Use in Speci\037c P)18.1 (opula)-9.8 (tions \(8.3\)])]TJ /T1_1 1 Tf [( and males must comply with)-20 ( )]TJ -0.017 Tc 0.048 Tw -4.92 -1.087 Td (contraception requirements )Tj /T1_0 1 Tf [([see Use in Speci\037c P)18.2 (opula)-9.7 (tions \(8.3\)])]TJ /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.017 Tc 0.017 Tw -1.508 -1.537 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.008 Tc 0.092 Tw 1.508 0 Td (Pharmacies must be certi\036ed with the\034)Tj /T1_2 1 Tf 14.516 0 Td (THALOMID REMS)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 6.737 0 Td [( program,)37.3 ( must only)-7.9 ( )]TJ -0.014 Tc 0.065 Tw -21.253 -1.087 Td [(dispense to pa)-10.2 (tients who are authorized to receive )36.6 (THALOMID and comply with)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.087 Td (REMS requirements.)Tj 0.034 Tc 0.302 Tw -2.7 -1.653 Td [(Further informa)-9.7 (tion about the\034)]TJ /T1_2 1 Tf 13.299 0 Td (THALOMID REMS)Tj /T1_1 1 Tf /Span<>> BDC ( )Tj EMC 7.536 0 Td [( program is a)-9.7 (vailable a)-9.7 (t)34 ( )]TJ -0.017 Tc 0.048 Tw -20.834 -1.068 Td [(www)37.2 (.celgeneriskmana)-9.8 (gement.com or by telephone a)-9.8 (t 1-888-423-5436.)]TJ /T1_2 1 Tf 0.017 Tw 36 86.406 Td (5.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(V)24.2 (enous and Arterial Thromboembolism)]TJ /T1_1 1 Tf -0.004 Tc 0.156 Tw -3.375 -1.604 Td [(The use of )37 (THALOMID in pa)-10.4 (tients with MM results in an increased risk of venous)-3.9 ( )]TJ -0.007 Tc 0.136 Tw 0 -1.064 Td [(t)0.5 (hr)0.5 (o)0.5 (mb)0.5 (o)0.5 (em)0.5 (b)0.5 (ol)0.5 (i)0.5 (sm)0.5 (,)37.5 ( s)0.5 (u)0.5 (ch)0.5 ( as)0.5 ( de)0.5 (e)0.5 (p v)0.5 (e)0.5 (no)0.5 (u)0.5 (s t)0.5 (hr)0.5 (o)0.5 (mb)0.5 (o)0.5 (si)0.5 (s)0.5 ( a)0.5 (n)0.5 (d p)0.5 (ul)0.5 (m)0.5 (on)0.5 (a)0.5 (r)-17.6 (y)0.5 ( e)0.5 (mb)0.5 (o)0.5 (li)0.5 (s)0.5 (m.)37.5 ( )36.7 (T)0.5 (h)0.5 (is)-7 ( )]TJ -0.002 Tc 0.162 Tw 0 -1.064 Td [(risk increases significantly when )36.6 (THALOMID is used in combina)-9.7 (tion with standard)-2 ( )]TJ -0.013 Tc 0.107 Tw 0 -1.064 Td [(chemothera)-9.7 (peutic a)-9.6 (gents inc)20.3 (luding dexamethasone.)37.3 ( In one controlled trial,)37.3 ( the ra)-9.7 (te of)-13 ( )]TJ -0.027 Tc 0.036 Tw 0 -1.064 Td [(venous thromboembolism was 22.5% in pa)-10.1 (tients receiving )37 (THALOMID in combina)-10 (tion with)-27 ( )]TJ -0.025 Tc 0.042 Tw 0 -1.064 Td [(dexamethasone compared to 4.9% in pa)-9.7 (tients receiving dexamethasone alone \()-39.8 (p)]TJ /Span<>> BDC ( )Tj EMC 28.436 0 Td (=)Tj /Span<>> BDC ( )Tj EMC 0.591 0 Td [(0.002)-19.8 (\).)]TJ -0.004 Tc 0.153 Tw -29.027 -1.739 Td [(Ischemic heart disease \(11.1%\),)37.1 ( inc)20.2 (luding myocardial infarction \(1.3%\),)37.1 ( and stroke)-4 ( )]TJ 0.005 Tc 0.2 Tw 0 -1.064 Td [(\(cerebrovascular accident,)36.8 ( 2.6%\) ha)-10.2 (ve also occurred in pa)-10.2 (tients with previously)5.1 ( )]TJ -0.013 Tc 0.111 Tw 0 -1.064 Td [(untrea)-10.2 (ted )0.5 (MM trea)-10.2 (ted )0.5 (with )37.5 (THALOMID )0.5 (and dexamethasone )0.5 (compared to placebo and)-13 ( )]TJ -0.015 Tc 0.098 Tw 0 -1.064 Td [(dexamethasone \(4.7%,)37.1 ( 1.7%,)37.1 ( and 0.9%,)37.1 ( respectively\) in one c)20.1 (linical trial )]TJ /T1_0 1 Tf 0.061 Tw [([see Adverse)-15 ( )]TJ -0.025 Tc 0.025 Tw 0 -1.064 Td (Reactio)Tj 0.048 Tw (ns \(6.1\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.019 Tc 0.078 Tw 0 -1.739 Td [(Consider thromboprophylaxis based on an assessment of individual pa)-9.8 (tients\222 underlying)-19 ( )]TJ -0.014 Tc 0.101 Tw 0 -1.064 Td [(r)0.5 (i)0.5 (sk)0.5 ( f)0.5 (ac)0.5 (t)0.5 (o)0.5 (r)0.5 (s)0.5 (.)37.4 ( P)18.5 (a)-9.6 (t)0.5 (i)0.5 (e)0.5 (nt)0.5 (s)0.5 ( a)0.5 (nd)0.5 ( p)0.5 (hy)0.5 (s)0.5 (i)0.5 (ci)0.5 (a)0.5 (n)0.5 (s s)0.5 (ho)0.5 (u)0.5 (l)0.5 (d b)0.5 (e)0.5 ( o)0.5 (b)0.5 (s)0.5 (er)-17.5 (v)0.5 (a)0.5 (n)0.5 (t)0.5 ( f)0.5 (o)0.5 (r)0.5 ( t)0.5 (h)0.5 (e)0.5 ( si)0.5 (g)0.5 (n)0.5 (s a)0.5 (n)0.5 (d s)0.5 (ym)0.5 (p)0.5 (t)0.5 (o)0.5 (m)0.5 (s)-14.1 ( )]TJ -0.013 Tc 0.109 Tw 0 -1.064 Td [(of thromboembolism.)37.1 ( )37.4 (Advise )0.5 (pa)-9.9 (tients )0.5 (to )0.5 (seek )0.5 (immedia)-9.9 (te medical )0.5 (care )0.5 (if )0.5 (they )0.5 (develop)-13 ( )]TJ -0.015 Tc 0.098 Tw 0 -1.064 Td [(symptoms such )0.5 (as shortness )0.5 (of brea)-9.8 (th,)37.3 ( chest )0.5 (pain,)37.2 ( )0.5 (or arm or )0.5 (leg )0.5 (s)-9.8 (welling )]TJ /T1_0 1 Tf 27.469 0 Td [([see Boxed)-15.1 ( )]TJ -0.027 Tc 0.027 Tw -27.469 -1.064 Td [(W)18.3 (arning])]TJ /T1_1 1 Tf 0.036 Tw [(.)37.2 ( )37.3 (Agents tha)-9.7 (t also may increase the risk of thromboembolism should be used with)-27 ( )]TJ -0.025 Tc 0.048 Tw 0 -1.083 Td [(caution in pa)-9.8 (tients receiving )37.2 (THALOMID )]TJ /T1_0 1 Tf ([see Drug Interactio)Tj (ns \(7.7\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_2 1 Tf -0.017 Tc 0.017 Tw 0 -1.912 Td (5.4)Tj /Span<>> BDC ( )Tj EMC -0.013 Tc 0.067 Tw 3.375 0 Td [(Incr)0.5 (eased )0.5 (Mor)0.5 (talit)0.5 (y )0.5 (in )0.5 (P)24.4 (atie)0.5 (nts )0.5 (with )0.5 (M)0.5 (M W)0.5 (hen )0.5 (P)24.4 (embroli)0.5 (zumab )0.5 (Is)0.5 ( A)0.5 (dded)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.102 Td [(to a Thalidomide Analogue and De)10.2 (xamethasone)]TJ /T1_1 1 Tf -0.018 Tc 0.036 Tw -3.375 -1.623 Td [(In two randomized c)19.8 (linical trials in pa)-10.2 (tients with MM,)36.8 ( the addition of pembrolizumab to a)-17.9 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.083 Td [(thalidomide analogue plus dexamethasone,)36.7 ( a use for which no PD-1 or PD-L1 blocking)-16.1 ( )]TJ -0.019 Tc 0.036 Tw 0 -1.083 Td [(antibod)-10 (y is indica)-10 (ted,)37 ( resulted in increased mortality)55 (.)37 ( )37 (T)74 (rea)-10 (tment of pa)-10 (tients with MM with)-19 ( )]TJ -0.008 Tc 0.096 Tw 0 -1.083 Td [(a PD-1 or PD-L1 blocking antibod)-10.3 (y in combina)-10.4 (tion with a thalidomide analogue plus)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.083 Td [(dexamethasone is not recommended outside of controlled c)20.2 (linical trials.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.912 Td (5.5)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Drowsiness and Somnolence)Tj /T1_1 1 Tf 0.016 Tc 0.211 Tw -3.375 -1.623 Td [(T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.5 (I)0.5 (D)0.5 ( f)0.5 (r)0.5 (e)0.5 (q)0.5 (u)0.5 (e)0.5 (n)0.5 (t)0.5 (l)0.5 (y)0.5 ( c)0.5 (a)0.5 (u)0.5 (s)0.5 (e)0.5 (s)0.5 ( d)0.5 (r)0.5 (o)-9.5 (w)0.5 (s)0.5 (i)0.5 (n)0.5 (e)0.5 (s)0.5 (s)0.5 ( a)0.5 (n)0.5 (d)0.5 ( s)0.5 (o)0.6 (m)0.5 (n)0.5 (o)0.5 (l)0.5 (e)0.5 (n)0.5 (c)0.5 (e)0.5 (.)37.5 ( P)18.5 (a)-9.5 (t)0.5 (i)0.5 (e)0.5 (n)0.5 (t)0.5 (s)0.5 ( s)0.5 (h)0.5 (o)0.5 (u)0.5 (l)0.5 (d)0.5 ( b)0.5 (e)16 ( )]TJ -0.004 Tc 0.115 Tw 0 -1.083 Td [(instructed to a)-10.1 (void situa)-10.1 (tions where dro)-10.1 (wsiness may be a problem and not to take)-3.9 ( )]TJ -0.008 Tc 0.094 Tw 0 -1.083 Td [(other )0.5 (medica)-9.9 (tions tha)-9.9 (t may )0.5 (cause dro)-9.9 (wsiness )0.5 (without adequa)-9.9 (te medical )0.5 (advice )]TJ /T1_0 1 Tf 0.008 Tw [([see)-8 ( )]TJ -0.015 Tc 0.061 Tw 0 -1.083 Td [(Drug Interactions )0.5 (\(7.1\)])]TJ /T1_1 1 Tf [(.)36.8 ( )37.4 (Advise )0.5 (pa)-10.2 (tients as to the possible impairment of )0.5 (mental )0.5 (and/or)-15 ( )]TJ -0.017 Tc 0.054 Tw 0 -1.083 Td [(physical abilities required for the performance of hazardous tasks,)37.2 ( such as driving a car)-17 ( )]TJ 0.048 Tw 0 -1.083 Td [(or opera)-9.8 (ting other complex or dangerous machiner)-17.8 (y)55.2 (.)37.2 ( Dose reductions may be required.)]TJ /T1_2 1 Tf 0.017 Tw 0 -1.912 Td (5.6)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(P)24.2 (eripheral Neuropathy)]TJ /T1_1 1 Tf 0.004 Tc 0.156 Tw -3.375 -1.623 Td [(THALOMID is kno)-10.3 (wn to cause ner)-18.3 (ve dama)-10.4 (ge tha)-10.3 (t may be permanent.)36.7 ( P)17.6 (eripheral)4 ( )]TJ -0.011 Tc 0.077 Tw 0 -1.083 Td [(neuropa)-9.7 (thy is a common \(\03710%\) and potentially severe adverse reaction of t\ rea)-9.7 (tment)-11 ( )]TJ 0.006 Tc 0.163 Tw 0 -1.083 Td [(with )37.4 (THALOMID )0.5 (tha)-9.8 (t may be )0.5 (irreversible.)37.2 ( )0.5 (P)18.2 (eripheral )0.5 (neuropa)-9.8 (thy generally )0.5 (occurs)6 ( )]TJ -0.017 Tc 0.037 Tw 0 -1.083 Td [(follo)-9.7 (wing chronic use over a period of months; ho)-9.8 (wever)74.2 (,)37.2 ( peripheral neuropa)-9.8 (thy follo)-9.8 (wing)-17 ( )]TJ -0.006 Tc 0.102 Tw 0 -1.083 Td [(re)0.5 (la)-9.6 (t)0.5 (ivel)0.5 (y )0.5 (sho)0.5 (rt-t)0.5 (erm)0.5 ( )0.5 (use)0.5 ( )0.5 (has )0.6 (been)0.5 ( )0.5 (repo)0.5 (rte)0.5 (d.)37.4 ( )37.5 (The)0.5 ( )0.5 (cor)0.5 (rel)0.5 (a)-9.6 (tio)0.5 (n )0.5 (wi)0.5 (th )0.5 (cu)0.5 (mula)-9.5 (tive)0.5 ( )0.5 (dos)0.5 (e )0.5 (is)-6 ( )]TJ -0.015 Tc 0.061 Tw 0 -1.083 Td [(unc)19.7 (lear)73.7 (.)36.7 ( Symptoms may occur some time after )37.3 (THALOMID trea)-10.3 (tment has been stopped)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.083 Td [(and may resolve slo)-9.8 (wly or not a)-9.8 (t all.)]TJ 0.001 Tc 0.136 Tw 0 -1.803 Td [(F)24.4 (e)0.5 (w r)0.5 (ep)0.5 (or)0.5 (ts o)0.5 (f n)0.5 (eu)0.5 (ro)0.5 (pa)-9.5 (thy)0.5 ( ha)-9.5 (ve)0.5 ( ar)0.5 (is)0.5 (en i)0.5 (n th)0.5 (e t)0.5 (re)0.5 (a)-9.6 (t)0.5 (me)0.5 (nt)0.5 ( of)0.5 ( ENL)0.5 ( de)0.5 (sp)0.5 (it)0.5 (e lo)0.5 (ng)0.5 (-t)0.5 (erm)1.1 ( )]TJ 0.01 Tc 0.181 Tw 0 -1.083 Td [(T)0.5 (H)0.5 (A)0.5 (L)0.6 (O)0.5 (M)0.5 (I)0.5 (D)0.5 ( t)0.5 (r)0.5 (e)0.5 (a)-9.5 (t)0.6 (m)0.5 (e)0.5 (n)0.5 (t)0.5 (.)37.5 ( H)0.5 (o)-9.5 (w)0.6 (e)0.5 (v)0.5 (e)0.5 (r)74.5 (,)37.5 ( t)0.5 (h)0.5 (e)0.5 ( i)0.5 (n)0.5 (a)0.6 (b)0.5 (i)0.5 (l)0.5 (i)0.5 (t)0.5 (y)0.5 ( c)20.5 (l)0.5 (i)0.5 (n)0.5 (i)0.6 (c)0.5 (a)0.5 (l)0.5 (l)0.5 (y)0.5 ( t)0.5 (o)0.5 ( d)0.5 (i)0.5 (f)0.5 (f)0.6 (e)0.5 (r)0.5 (e)0.5 (n)0.5 (t)0.6 (i)0.5 (a)-9.5 (t)0.5 (e)0.5 ( )37.1 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.6 (I)0.5 (D)10 ( )]TJ 0 Tc 0.132 Tw 0 -1.083 Td [(neuropa)-9.6 (thy from the neuropa)-9.6 (thy often seen in ENL makes it dif\036cult to determine )]TJ -0.013 Tc 0.068 Tw 0 -1.083 Td [(accura)-9.9 (tely the incidence of )36.5 (THALOMID-rela)-9.9 (ted neuropa)-9.9 (thy in pa)-9.9 (tients with ENL trea)-9.9 (ted)-13 ( )]TJ -0.017 Tc 0.011 Tw 0 -1.083 Td (with THALOMID.)Tj -0.01 Tc 0.081 Tw 0 -1.803 Td [(P)18.5 (a)-9.5 (t)0.5 (i)0.5 (e)0.6 (nt)0.6 (s)0.5 ( s)0.5 (ho)0.6 (u)0.5 (l)0.5 (d)0.5 ( b)0.5 (e)0.5 ( e)0.5 (x)0.5 (a)0.5 (m)0.5 (i)0.5 (n)0.5 (e)0.5 (d)0.6 ( a)-9.5 (t)0.6 ( m)0.5 (o)0.6 (n)0.5 (t)0.5 (h)0.5 (l)0.5 (y)0.5 ( i)0.5 (n)0.5 (t)0.5 (e)0.5 (r)-17.5 (v)0.6 (a)0.5 (l)0.5 (s)0.5 ( f)0.5 (o)0.5 (r)0.5 ( t)0.5 (h)0.5 (e)0.5 ( \036)0.5 (r)0.5 (s)0.5 (t)0.5 ( 3)0.5 ( m)0.5 (o)0.5 (n)0.5 (t)0.5 (h)0.5 (s)0.5 ( o)0.5 (f)0.5 ( )37 (T)0.5 (H)0.5 (A)0.5 (L)0.5 (O)0.5 (M)0.6 (I)0.5 (D)-10 ( )]TJ 0.002 Tc 0.144 Tw 0 -1.083 Td [(thera)-10 (py to enable the c)20 (linician to detect early signs of neuropa)-10 (thy)55 (,)36.9 ( which inc)19.9 (lude)2 ( )]TJ 0.007 Tc 0.171 Tw 0 -1.083 Td [(numbness,)36.6 ( tingling or pain in the hands and feet.)36.7 ( P)17.6 (a)-10.3 (tients should be evalua)-10.3 (ted)7 ( )]TJ 0.009 Tc 0.178 Tw 0 -1.083 Td [(periodically thereafter during trea)-9.8 (tment.)37.2 ( P)18.2 (a)-9.8 (tients should be regularly counseled,)46 ( )]TJ -0.021 Tc 0.036 Tw 0 -1.083 Td [(questioned,)36.6 ( and evalua)-10.3 (ted for signs or symptoms of peripheral neuropa)-10.3 (thy)54.6 (.)36.6 ( Considera)-10.3 (tion)-21 ( )]TJ -0.01 Tc 0.081 Tw 0 -1.083 Td [(s)0.5 (h)0.5 (o)0.5 (u)0.6 (l)0.5 (d)0.5 ( b)0.5 (e)0.5 ( g)0.6 (i)0.5 (v)0.5 (e)0.5 (n)0.5 ( t)0.6 (o)0.5 ( e)0.5 (l)0.5 (e)0.6 (c)0.5 (t)0.5 (r)0.5 (o)0.5 (p)0.5 (h)0.6 (y)0.5 (s)0.5 (i)0.5 (o)0.5 (l)0.5 (o)0.6 (g)0.5 (i)0.5 (c)0.5 (a)0.5 (l)0.5 ( t)0.6 (e)0.5 (s)0.5 (t)0.5 (i)0.5 (n)0.5 (g)0.6 (,)37.4 ( c)0.5 (o)0.5 (n)0.5 (s)0.5 (i)0.5 (s)0.5 (t)0.6 (i)0.5 (n)0.5 (g)0.5 ( o)0.6 (f)0.5 ( m)0.5 (e)0.6 (a)0.5 (s)0.5 (u)0.5 (r)0.5 (e)0.5 (m)0.6 (e)0.5 (n)0.5 (t)0.5 ( o)0.5 (f)0.6 ( s)0.5 (e)0.5 (n)0.5 (s)0.5 (o)0.6 (r)-17.5 (y)-10 ( )]TJ -0.012 Tc 0.073 Tw 0 -1.083 Td [(ner)-17.7 (ve action potential \(SNAP\) amplitudes a)-9.8 (t baseline and thereafter ever)-17.8 (y 6 months in)-12 ( )]TJ -0.013 Tc 0.068 Tw 0 -1.083 Td [(an effort to detect asymptoma)-9.9 (tic neuropa)-9.8 (thy)55.2 (.)37.1 ( If symptoms of drug-induced neuropa)-9.9 (thy)-13 ( )]TJ -0.002 Tc 0.124 Tw 0 -1.083 Td [(develop,)36.9 ( )36.6 (THALOMID should be discontinued immedia)-10 (tely to limit further dama)-10 (ge,)37 ( if)-2 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.083 Td [(c)19.8 (linically a)-10.2 (ppropria)-10.2 (te.)36.8 ( Usually)54.8 (,)36.7 ( trea)-10.1 (tment with )36.7 (THALOMID should only be reinitia)-10.2 (ted if the)-17 ( )]TJ 0.048 Tw 0 -1.083 Td [(neuropa)-9.7 (thy returns to baseline sta)-9.8 (tus.)]TJ -0.009 Tc 0.088 Tw 0 -1.803 Td [(Medica)-9.7 (tions kno)-9.7 (wn )0.5 (to be associa)-9.7 (ted with )0.5 (neuropa)-9.7 (thy )0.5 (should )0.5 (be used )0.5 (with )0.5 (caution )0.5 (in)-9 ( )]TJ -0.017 Tc 0.011 Tw 0 -1.083 Td [(pa)-9.8 (tients )-36.8 (receiving THALOMID )]TJ /T1_0 1 Tf 0.048 Tw 10.612 0 Td ([see Drug Interactio)Tj (ns \(7.3\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_2 1 Tf -0.017 Tc 0.017 Tw -10.612 -1.912 Td (5.7)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Dizziness and Orthostatic Hypotension)Tj /T1_1 1 Tf -0.008 Tc 0.097 Tw -3.375 -1.623 Td [(P)17.6 (a)-10.5 (tients should also be advised tha)-10.5 (t )37.3 (THALOMID may cause dizziness and orthosta)-10.4 (tic)-7.9 ( )]TJ 0 Tc 0.132 Tw 0 -1.083 Td [(hypotension and tha)-9.7 (t,)37.3 ( therefore,)37.3 ( they should sit upright for a few minutes prior to )]TJ -0.017 Tc 0.048 Tw 0 -1.083 Td (standing up from a recumbent position.)Tj /T1_2 1 Tf 0.017 Tw 0 -1.912 Td (5.8)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td (Neutropenia)Tj /T1_1 1 Tf 0.005 Tc 0.156 Tw -3.375 -1.623 Td [(D)0.5 (e)0.5 (c)0.5 (r)0.5 (e)0.5 (a)0.5 (s)0.5 (e)0.5 (d)0.5 ( wh)0.5 (i)0.5 (t)0.5 (e)0.5 ( b)0.5 (l)0.5 (o)0.5 (o)0.5 (d)0.5 ( c)0.5 (e)0.6 (ll)0.5 ( c)0.5 (o)0.5 (u)0.5 (n)0.5 (t)0.5 (s)0.5 (,)37.5 ( i)0.5 (n)0.5 (c)20.5 (l)0.5 (u)0.5 (d)0.5 (i)0.5 (n)0.5 (g)0.5 ( n)0.5 (e)0.5 (u)0.5 (t)0.5 (r)0.5 (o)0.5 (p)0.5 (e)0.5 (n)0.5 (i)0.5 (a)0.5 (,)37.5 ( h)0.6 (a)-9.5 (v)0.5 (e)0.5 ( b)0.5 (e)0.5 (e)0.5 (n)0.5 ( r)0.5 (e)0.5 (p)0.5 (o)0.5 (r)0.5 (t)0.5 (e)0.5 (d)0.5 ( i)0.5 (n)5 ( )]TJ -0.009 Tc 0.088 Tw 0 -1.083 Td [(associa)-9.8 (tion with the c)20.1 (linical use of )37.1 (THALOMID.)37.2 ( )37.2 (T)74.1 (rea)-9.8 (tment should not be initia)-9.8 (ted with)-9 ( )]TJ -0.017 Tc 0.043 Tw 0 -1.083 Td (an absolute neutrophil count \(ANC\) of <750/mm)Tj 0 Tc 0 Tw 5.6 0 0 5.6 461.9322 81.9745 Tm (3)Tj -0.017 Tc 0.043 Tw 8 0 0 8 464.5239 79.3105 Tm [(.)37.2 ( )36.7 (White blood cell count and differential)-16.9 ( )]TJ -0.02 Tc 0.036 Tw -17.565 -1.083 Td [(should be monitored on an ongoing basis,)36.7 ( especially in pa)-10.3 (tients who may be more prone)-20 ( )]TJ -0.01 Tc 0.084 Tw 0 -1.083 Td [(to neutropenia,)37.1 ( such as pa)-9.9 (tients who are HIV)18.1 (-seropositive.)37.1 ( If )37.3 (ANC decreases to belo)-10 (w)-9.9 ( )]TJ -0.014 Tc 0.014 Tw 0 -1.083 Td (750/mm)Tj 0 Tc 0 Tw 5.6 0 0 5.6 348.6188 55.9882 Tm (3)Tj -0.014 Tc 0.063 Tw 8 0 0 8 351.2278 53.3242 Tm [( while on trea)-9.9 (tment,)37.1 ( the pa)-9.9 (tient\222)55.1 (s medica)-9.8 (tion regimen should be re-evalua)-9.9 (ted)-14 ( )]TJ -0.017 Tc 0.041 Tw -3.403 -1.083 Td [(and,)37.2 ( if the neutropenia persists,)37.2 ( considera)-9.8 (tion should be given to withholding )37.2 (THALOMID)-17.1 ( )]TJ 0.048 Tw 0 -1.083 Td [(if c)20.2 (linically a)-9.8 (ppropria)-9.8 (te.)]TJ ET endstream endobj 107 0 obj <>stream 4 M /GS0 gs q 1 0 0 1 36 573.688 cm 0 0 m 540 0 l S Q BT /T1_0 1 Tf -0.017 Tc 0.048 Tw 8 0 0 8 36 750.2881 Tm [(HIGHLIGHTS OF PRESCRIBING INFORMA)55.2 (TION)]TJ /T1_1 1 Tf 0.017 Tw 3.125 -1.608 Td (7.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Drugs which Cause P)18.3 (eripheral Neuropa)-9.8 (thy)]TJ 0.017 Tw -3 -1.316 Td (7.4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td (Hormonal Contraceptives)Tj 0.017 Tw -3 -1.316 Td (7.5)Tj /Span<>> BDC ( )Tj EMC 3 0 Td [(W)18.2 (arfarin)]TJ -3 -1.316 Td (7.6)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Drugs tha)-9.8 (t Interfere with Hormonal Contraceptives)]TJ 0.017 Tw -3 -1.316 Td (7.7)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Concomitant )37.2 (Thera)-9.8 (pies tha)-9.8 (t may Increase the Risk of)-17 ( )]TJ 0.017 Tw 0 -1.091 Td (Thromboembolism)Tj /T1_0 1 Tf -6.125 -1.427 Td (8)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(USE IN SPECIFIC POPULA)55.2 (TIONS)]TJ /T1_1 1 Tf 0.017 Tw 8 0 0 8.0947 61 663.6617 Tm (8.1)Tj /Span<>> BDC ( )Tj EMC 3 0 Td [(Pregnanc)20.2 (y)]TJ -3 -1.29 Td (8.2)Tj /Span<>> BDC ( )Tj EMC 3 0 Td [(Lacta)-9.8 (tion)]TJ -3 -1.29 Td (8.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(F)24.2 (emales and Males of Reproductive P)18.2 (otential)]TJ 0.017 Tw -3 -1.29 Td (8.4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(P)18.2 (edia)-9.7 (tric Use)]TJ 0.017 Tw -3 -1.29 Td (8.5)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Geria)-9.7 (tric Use)]TJ /T1_0 1 Tf 0.017 Tw 8 0 0 8 36 611.0195 Tm (9)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(DR)-9.8 (UG ABUSE AND DEPENDENCE)]TJ 0.017 Tw -3.125 -1.494 Td (10)Tj /Span<>> BDC ( )Tj EMC 3.125 0 Td (OVERDOSAGE)Tj -3.125 -1.494 Td (11)Tj /Span<>> BDC ( )Tj EMC 3.125 0 Td (DESCRIPTION)Tj /T1_2 1 Tf 0 Tc 0 Tw 14.029 20.408 Td (\()Tj -0.017 Tc 0.017 Tw 0.224 0 Td (Continued\))Tj /T1_0 1 Tf 18.622 -1.541 Td (12)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(CLINIC)18.2 (AL PHARMACOLOGY)]TJ /T1_1 1 Tf 0.017 Tw 0 -1.311 Td (12.1)Tj /Span<>> BDC ( )Tj EMC 0.011 Tw 3 0 Td [(Mechanism )-36.8 (of Action)]TJ 0.017 Tw -3 -1.244 Td (12.3)Tj /Span<>> BDC ( )Tj EMC 3 0 Td (Pharmacokinetics)Tj /T1_0 1 Tf -6.125 -1.355 Td (13)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(NONCLINIC)18.2 (AL TOXICOLOGY)]TJ /T1_1 1 Tf 0.017 Tw 0 -1.311 Td (13.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Carcinogenesis,)37.2 ( Muta)-9.8 (genesis,)37.2 ( Impairment of F)24.2 (ertility)]TJ /T1_0 1 Tf 0.017 Tw -6.125 -1.355 Td (14)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(CLINIC)18.2 (AL STUDIES)]TJ /T1_1 1 Tf 0.017 Tw 0 -1.311 Td (14.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td (Multiple Myeloma \(MM\))Tj 0.017 Tw -3 -1.244 Td (14.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Er)-17.8 (ythema Nodosum Leprosum \(ENL\))]TJ /T1_0 1 Tf 0.017 Tw -6.125 -1.355 Td (15)Tj /Span<>> BDC ( )Tj EMC 3.125 0 Td (REFERENCES)Tj -3.125 -1.423 Td (16)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td (HOW SUPPLIED/STORAGE AND HANDLING)Tj /T1_1 1 Tf 0.017 Tw 0 -1.311 Td (16.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td [(Ho)-9.8 (w Supplied)]TJ 0.017 Tw -3 -1.244 Td (16.2)Tj /Span<>> BDC ( )Tj EMC 3 0 Td [(Stora)-9.7 (ge)]TJ -3 -1.244 Td (16.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3 0 Td (Handling and Disposal)Tj /T1_0 1 Tf 0.017 Tw -6.125 -1.355 Td (17)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.125 0 Td [(P)54.2 (A)55.2 (TIENT COUNSELING INFORMA)55.2 (TION)]TJ /T1_1 1 Tf -0.005 Tc 0.086 Tw -3.125 -1.805 Td [(*Sections or subsections omitted from the full prescribing informa)-10.4 (tion are not listed.)]TJ /T1_0 1 Tf -0.017 Tc 0.048 Tw -36 -4.969 Td [(FULL PRESCRIBING INFORMA)55.1 (TION)]TJ ET 0.5 w 10 M q 1 0 0 1 43.7 509.0911 cm 0 0 m 77.591 0 l S Q q 1 0 0 1 43.7 383.1111 cm 0 0 m 91.414 0 l S Q BT 8 0 0 8 52.0339 524.1311 Tm [(W)18.2 (ARNING: EMBR)18.2 (Y)20.2 (O-FET)55.2 (AL TOXICITY AND VENOUS THROMBOEMBOLISM)]TJ -1.042 -1.692 Td [(EMBR)18.2 (Y)20.2 (O-FET)55.1 (AL TOXICITY)]TJ -0.008 Tc 0.095 Tw 0 -1.535 Td [(If THALOMID \(thalidomide\) is taken during pregnanc)9.8 (y)54.9 (,)36.9 ( it can cause severe)-8 ( )]TJ -0.002 Tc 0.125 Tw 0 -1.062 Td [(birth defects or embr)-18.2 (yo-fetal death.)36.8 ( THALOMID should never be used by)-2 ( )]TJ -0.012 Tc 0.072 Tw 0 -1.062 Td [(females who are pregnant or who could become pregnant while taking the)-12 ( )]TJ -0.003 Tc 0.121 Tw 0 -1.062 Td [(drug.)36.8 ( Even )0.5 (a single )0.5 (dose [1 )0.5 (capsule \(regardless )0.5 (of strength\)] )0.5 (taken )0.5 (by a)-3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(pregnant woman during her pregnanc)10.2 (y can cause severe birth defects.)]TJ 0.06 Tw 0 -1.423 Td [(Because of this toxicity and in an effort to make the chance of embr)-18.1 (yo-fetal)-17 ( )]TJ -0.014 Tc 0.064 Tw 0 -1.062 Td [(e)10 (xposure to THALOMID as negligible as possible,)37 ( THALOMID is appro)-10 (ved for)-14 ( )]TJ -0.016 Tc 0.06 Tw 0 -1.062 Td [(marketing only through a special restricted distribution program: THALOM\ ID)-16 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(REMS program,)37.2 ( appro)-9.8 (ved by the Food and Drug Administration.)]TJ 0.002 Tc 0.142 Tw 0 -1.423 Td [(Y)80.3 (ou can get the information about THALOMID and the THALOMID REMS)2 ( )]TJ -0.013 Tc 0.069 Tw 0 -1.062 Td [(program on the Internet at www)36.9 (.celgeneriskmanagement.com or by calling)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(the manuf)20.2 (acturer\222)37.2 (s toll-free number 1-888-423-5436.)]TJ 0 -1.805 Td (VENOUS THROMBOEMBOLISM)Tj 0.002 Tc 0.142 Tw 0 -1.535 Td [(The use of THALOMID in multiple myeloma results in an increased risk)2 ( )]TJ 0.02 Tc 0.234 Tw 0 -1.062 Td [(of venous thromboembolism,)37 ( such as deep venous thrombosis and)20 ( )]TJ 0.004 Tc 0.152 Tw 0 -1.062 Td [(pulmonar)-17.7 (y embolism.)37.3 ( This risk increases significantly when THALOMID)4 ( )]TJ -0.005 Tc 0.111 Tw 0 -1.062 Td [(is used in combination with standard chemotherapeutic agents inc)19.7 (luding)-5 ( )]TJ -0.017 Tc 0.059 Tw 0 -1.062 Td [(de)10.2 (xamethasone.)37.2 ( In )0.5 (one controlled trial,)37.2 ( the )0.5 (rate of venous )0.5 (thromboembolism)-17 ( )]TJ 0.033 Tc 0.3 Tw 0 -1.062 Td [(was 22.5% in patients receiving THALOMID in combination with)33 ( )]TJ 0.001 Tc 0.136 Tw 0 -1.062 Td [(de)10.4 (x)0.5 (a)0.5 (met)0.5 (has)0.5 (one)0.5 ( com)0.5 (pa)0.5 (red)0.5 ( to 4.)0.5 (9%)0.5 ( i)0.5 (n pa)0.5 (ti)0.5 (ent)0.5 (s re)0.5 (cei)0.5 (vi)0.5 (ng de)10.5 (xa)0.5 (met)0.5 (ha)0.5 (son)0.5 (e)1 ( )]TJ -0.017 Tc 0.055 Tw 0 -1.062 Td (alone \(p)Tj /Span<>> BDC ( )Tj EMC 3.142 0 Td (=)Tj /Span<>> BDC ( )Tj EMC 0.607 0 Td [(0.002\).)37.2 ( P)24.2 (atients and physicians are advised to be obser)-17.7 (v)16.2 (ant for the)-16.9 ( )]TJ -0.016 Tc 0.06 Tw -3.749 -1.062 Td [(si)0.5 (gn)0.5 (s )0.5 (an)0.5 (d s)0.5 (ym)0.5 (pt)0.5 (om)0.5 (s o)0.5 (f )0.5 (th)0.5 (ro)0.5 (mbo)0.5 (em)0.5 (bol)0.5 (is)0.5 (m.)37.4 ( )0.5 (In)0.5 (st)0.5 (ru)0.5 (ct )0.5 (pa)0.5 (ti)0.5 (en)0.5 (ts)0.5 ( t)0.5 (o s)0.5 (ee)0.5 (k )0.5 (med)0.5 (ic)0.5 (al)-16 ( )]TJ -0.01 Tc 0.085 Tw 0 -1.062 Td [(care if they develop symptoms such as shortness of breath,)36.9 ( chest pain,)36.9 ( or)-10 ( )]TJ -0.013 Tc 0.071 Tw 0 -1.062 Td [(arm )0.5 (or )0.5 (leg )0.5 (swelling.)36.7 ( )0.6 (Consider )0.5 (thromboprophylaxis )0.5 (based )0.5 (on )0.6 (an )0.5 (assessment)-12.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(of individual patients\222 underlying risk f)20.1 (actors.)]TJ ET 1 w 4 M 36 271.131 252 266.412 re S BT 0.017 Tw 8 0 0 8 36 253.4781 Tm (1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(INDIC)18.2 (A)55.2 (TIONS AND USAGE)]TJ 0.017 Tw -3.375 -1.837 Td (1.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Multiple Myeloma)Tj /T1_1 1 Tf -0.018 Tc 0.036 Tw -3.375 -1.593 Td [(THALOMID in combina)-9.6 (tion with dexamethasone is indica)-9.6 (ted for the trea)-9.6 (tment of pa)-9.6 (tients)-18 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.053 Td [(with newly dia)-9.8 (gnosed multiple myeloma \(MM\) )]TJ /T1_2 1 Tf ([see Clinical Studie)Tj (s \(14.1\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -1.882 Td (1.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Er)-17.8 (ythema Nodosum Leprosum)]TJ /T1_1 1 Tf -0.001 Tc 0.127 Tw -3.375 -1.593 Td [(THALOMID is indica)-9.6 (ted for the acute trea)-9.6 (tment of the c)0.5 (uta)0.5 (neo)0.5 (us manifesta)-9.6 (tions of)-1 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.053 Td [(modera)-9.8 (te to severe er)-17.8 (ythema nodosum leprosum \(ENL\).)]TJ -0.013 Tc 0.068 Tw 0 -1.773 Td [(THALOMID )0.5 (is )0.6 (not )0.5 (indica)-9.7 (ted )0.5 (as )0.6 (monothera)-9.7 (py )0.5 (for )0.5 (such )0.5 (ENL )0.5 (trea)-9.7 (tment )0.6 (in )0.5 (the )0.6 (presence )0.6 (of)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.053 Td [(modera)-9.8 (te to severe neuritis.)]TJ -0.014 Tc 0.065 Tw 0 -1.773 Td [(THALOMID is also indica)-10.2 (ted as maintenance thera)-10.1 (py for prevention and suppression of)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.053 Td [(the cutaneous manifesta)-9.8 (tions of ENL recurrence )]TJ /T1_2 1 Tf ([see Clinical Studie)Tj (s \(14.2\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -2.057 Td (2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(DOSAGE AND ADMINISTRA)55.2 (TION)]TJ 0.017 Tw -3.375 -1.837 Td (2.1)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Required Baseline T)74.2 (esting)]TJ /T1_1 1 Tf -0.002 Tc 0.122 Tw -3.375 -1.593 Td [(Drug prescribing to females of reproductive potential is contingent upon\ initial and)-2 ( )]TJ -0.005 Tc 0.11 Tw 0 -1.053 Td [(continued nega)-10.2 (tive results of pregnanc)19.9 (y testing )]TJ /T1_2 1 Tf [([see )37.2 (W)17.9 (arnings and Precautions \(5.1)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.053 Td (and 5.2\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj -0.018 Tc 0.036 Tw 0 -1.773 Td [(THALOMID must only be administered in compliance with all of the terms o\ utlined in the)-18 ( )]TJ -0.012 Tc 0.072 Tw 0 -1.053 Td [(THALOMID REMS program.)37.3 ( )36.9 (THALOMID may only be prescribed by prescribers certi\036ed)-12 ( )]TJ -0.017 Tc 0.039 Tw 0 -1.053 Td [(with the )36.9 (THALOMID REMS program and may only be dispensed by pharmacists certi\036\ ed)-17.1 ( )]TJ 0.048 Tw 0 -1.053 Td [(with the )37.2 (THALOMID REMS program.)]TJ /T1_0 1 Tf 0.017 Tw 36 61.895 Td (2.2)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Recommended Dosage for Multiple Myeloma)Tj /T1_1 1 Tf -0.019 Tc 0.036 Tw -3.375 -1.592 Td [(The recommended dose of )37 (THALOMID \(thalidomide\) in combina)-9.9 (tion with dexamethasone)-19 ( )]TJ -0.021 Tc 0 -1.052 Td [(is 200 mg once daily \(in 28 day trea)-9.6 (tment c)20.4 (yc)20.4 (les\) orally with wa)-9.6 (ter)74.3 (,)37.4 ( preferably a)-9.6 (t bedtime)-21 ( )]TJ -0.014 Tc 0.061 Tw 0 -1.052 Td [(a)0.5 (n)0.5 (d a)-9.5 (t)0.5 ( l)0.5 (ea)0.5 (s)0.5 (t)0.5 ( 1)0.5 ( ho)0.5 (u)0.5 (r)0.5 ( af)0.5 (t)0.5 (e)0.5 (r)0.5 ( t)0.5 (he)0.5 ( e)0.5 (v)0.5 (e)0.5 (ni)0.5 (n)0.5 (g)0.5 ( me)0.5 (a)0.5 (l)0.5 (.)37.5 ( )36.8 (T)0.5 (h)0.5 (e)0.5 ( d)0.5 (o)0.5 (s)0.5 (e)0.5 ( o)0.5 (f d)0.5 (e)0.5 (x)0.5 (a)0.5 (me)0.5 (t)0.5 (h)0.5 (a)0.5 (s)0.5 (on)0.5 (e)0.5 ( i)0.5 (s 4)0.5 (0)0.5 ( m)0.5 (g d)0.5 (a)0.5 (i)0.5 (ly)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td [(administered orally on days 1-4,)37.2 ( 9-12,)37.2 ( and 17-20 ever)-17.7 (y 28 days.)]TJ /T1_0 1 Tf 0.017 Tw 0 -1.88 Td (2.3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td [(Recommended Dosage for Er)-17.8 (ythema Nodosum Leprosum)]TJ /T1_1 1 Tf 0 Tc 0.136 Tw -3.375 -1.591 Td [(The recommended dose of )37.2 (THALOMID for an episode of cutaneous ENL is 100 to )]TJ -0.017 Tc 0.051 Tw 0 -1.052 Td [(300 )0.5 (mg/day )0.5 (once )0.5 (daily )0.5 (orally with )0.5 (wa)-9.8 (ter)74.2 (,)37.2 ( preferably )0.5 (a)-9.8 (t bedtime and a)-9.8 (t least 1 )0.5 (hour )0.5 (after)-17 ( )]TJ 0.036 Tw 0 -1.052 Td [(t)0.5 (he)0.5 ( )0.5 (ev)0.5 (e)0.5 (ni)0.5 (n)0.5 (g )0.5 (m)0.5 (ea)0.5 (l)0.5 (.)37.4 ( )0.5 (I)0.5 (ni)0.5 (t)0.5 (ia)-9.5 (t)0.5 (e)0.5 ( d)0.5 (os)0.5 (i)0.5 (ng)0.5 ( )0.5 (fo)0.5 (r)0.5 ( p)0.5 (a)-9.5 (t)0.5 (ie)0.5 (n)0.5 (ts)0.5 ( w)0.5 (e)0.5 (ig)0.5 (h)0.5 (in)0.5 (g)0.5 ( l)0.5 (e)0.5 (ss)0.5 ( )0.5 (th)0.5 (a)0.5 (n )0.5 (50)0.5 ( )0.5 (k)0.5 (il)0.5 (o)0.5 (gr)0.5 (am)0.5 (s)0.5 ( )0.5 (a)-9.6 (t)0.5 ( )0.5 (th)0.5 (e)0.5 ( l)0.5 (o)-9.5 (w)-17 ( )]TJ 0.048 Tw 0 -1.052 Td (end of the dose range.)Tj -0.011 Tc 0.076 Tw 0 -1.772 Td [(C)0.5 (on)0.5 (si)0.5 (de)0.5 (r do)0.5 (si)0.5 (ng)0.5 ( i)0.5 (n t)0.5 (he)0.5 ( h)0.5 (ig)0.5 (he)0.5 (r)0.5 ( do)0.5 (s)0.5 (a)-9.6 (g)0.5 (e ra)0.5 (ng)0.5 (e fo)0.5 (r)0.5 ( pa)-9.5 (t)0.5 (ie)0.5 (nt)0.5 (s wi)0.5 (th)0.5 ( a)0.5 ( se)0.5 (v)0.5 (er)0.5 (e cu)0.5 (ta)0.5 (ne)0.5 (o)0.5 (us)0.5 ( E)0.5 (NL)-11 ( )]TJ -0.013 Tc 0.068 Tw 0 -1.052 Td [(reaction,)37.1 ( or in those who ha)-9.8 (ve previously required higher doses to control the reaction)-13 ( )]TJ -0.009 Tc 0.091 Tw 0 -1.052 Td [(\(possibly )0.5 (up )0.5 (to 400 mg/day\) once daily )0.5 (a)-10.3 (t bedtime or )0.5 (in )0.5 (divided )0.5 (doses with wa)-10.2 (ter)73.7 (,)36.7 ( )0.5 (a)-10.3 (t)-9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td (least 1 hour after meals.)Tj 0.047 Tw 0 -1.772 Td [(Consider concomitant use of corticosteroids in pa)-9.8 (tients with modera)-9.8 (te to severe neuritis)-17 ( )]TJ -0.014 Tc 0.063 Tw 0 -1.052 Td [(associa)-9.8 (ted with a severe ENL reaction.)37.2 ( Steroid usa)-9.8 (ge can be ta)-9.9 (pered and discontinued)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td [(when the neuritis has ameliora)-9.8 (ted.)]TJ -0.001 Tc 0.126 Tw 0 -1.772 Td [(Co)0.5 (ntinue dosi)0.5 (ng wi)0.5 (th )36.5 (TH)0.5 (ALOMID)0.5 ( unti)0.5 (l sign)0.5 (s an)0.5 (d sym)0.5 (ptoms)0.5 ( of act)0.5 (ive r)0.5 (eact)0.5 (ion h)0.5 (a)-9.6 (ve)-1 ( )]TJ 0.002 Tc 0.144 Tw 0 -1.052 Td [(subsided,)36.9 ( usually a period of a)-10.1 (t least 2 weeks.)36.9 ( P)17.9 (a)-10 (tients may then be ta)-10.1 (pered off)2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td [(medica)-9.8 (tion in 50 mg decrements ever)-17.8 (y 2 to 4 weeks.)]TJ 0.06 Tw 0 -1.772 Td [(P)17.6 (a)-10.3 (tients who ha)-10.3 (ve a documented histor)-18.4 (y of requiring prolonged maintenance trea)-10.3 (tment)-17 ( )]TJ -0.005 Tc 0.111 Tw 0 -1.052 Td [(to prevent the recurrence of cutaneous ENL or who \035are during ta)-10.3 (pering should be)-5 ( )]TJ 0.004 Tc 0.153 Tw 0 -1.052 Td [(maintained on the minimum dose necessar)-17.8 (y to control the reaction.)37.2 ( )37.2 (T)74.1 (a)-9.7 (pering off)4 ( )]TJ -0.01 Tc 0.085 Tw 0 -1.052 Td [(medica)-10.1 (tion should be a)-10.1 (ttempted ever)-18.1 (y 3 to 6 months,)36.9 ( in decrements of 50 mg ever)-18.1 (y)-10 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td (2 to 4 weeks.)Tj /T1_0 1 Tf 0.017 Tw 0 -1.88 Td (2.4)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (Dosage Modi\037cations for Adverse Reactions)Tj /T1_1 1 Tf -0.013 Tc 0.066 Tw -3.375 -1.591 Td [(I)0.5 (n)0.5 (t)0.6 (e)0.5 (r)0.5 (r)0.5 (u)0.6 (p)0.5 (t)0.5 ( )37.1 (T)0.5 (H)0.5 (A)0.5 (L)0.6 (O)0.5 (M)0.5 (I)0.5 (D)0.5 ( f)0.5 (o)0.6 (r)0.5 ( c)0.5 (o)0.5 (n)0.5 (s)0.6 (t)0.5 (i)0.5 (p)0.5 (a)-9.5 (t)0.6 (i)0.5 (o)0.5 (n)0.5 (,)37.5 ( s)0.6 (o)0.5 (m)0.5 (n)0.5 (o)0.6 (l)0.5 (e)0.5 (n)0.5 (c)0.5 (e)0.6 (,)37.5 ( o)0.5 (r)0.5 ( p)0.5 (e)0.5 (r)0.6 (i)0.5 (p)0.5 (h)0.5 (e)0.6 (r)0.5 (a)0.5 (l)0.5 ( n)0.5 (e)0.6 (u)0.5 (r)0.5 (o)0.5 (p)0.6 (a)-9.5 (t)0.5 (h)0.5 (y)55.5 (.)37.5 ( C)0.6 (o)0.5 (n)0.5 (s)0.5 (i)0.5 (d)0.5 (e)0.6 (r)0.5 ( a)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td [(reduced dose upon resumption of trea)-9.8 (tment.)20 ( )]TJ -0.003 Tc 0.117 Tw 0 -1.772 Td [(Consider dose reduction,)37.4 ( delay)55.4 (,)37.3 ( or discontinua)-9.6 (tion in pa)-9.6 (tients who develop Na)-9.6 (tional)-2.9 ( )]TJ -0.017 Tc 0.041 Tw 0 -1.052 Td [(Cancer Institute Common )36.6 (T)74.2 (oxicity Criteria \(NCI CTC\) Grade 3 or 4 adverse reactions and/)]TJ 0.048 Tw 0 -1.052 Td [(or based on c)20.2 (linical judgment.)]TJ -0.007 Tc 0.096 Tw 0 -1.772 Td [(P)18.5 (e)0.6 (r)0.5 (m)0.5 (a)0.6 (n)0.5 (e)0.5 (n)0.6 (t)0.5 (l)0.5 (y)0.6 ( d)0.6 (i)0.5 (s)0.5 (c)0.5 (o)0.6 (n)0.5 (t)0.5 (i)0.6 (n)0.5 (u)0.5 (e)0.6 ( )37.1 (T)0.5 (H)0.6 (A)0.5 (L)0.5 (O)0.5 (M)0.6 (I)0.5 (D)0.5 ( f)0.5 (o)0.6 (r)0.5 ( a)0.5 (n)0.5 (g)0.6 (i)0.5 (o)0.5 (e)0.6 (d)0.5 (e)0.5 (m)0.6 (a)0.5 (,)37.5 ( a)0.5 (n)0.5 (a)-9.4 (p)0.5 (h)0.5 (y)0.6 (l)0.5 (a)0.5 (x)0.6 (i)0.5 (s)0.5 (,)37.5 ( G)0.6 (r)0.5 (a)0.5 (d)0.5 (e)0.6 ( 4)0.6 ( r)0.6 (a)0.5 (s)0.5 (h)0.6 (,)37.5 ( s)0.6 (k)0.5 (i)0.5 (n)-7 ( )]TJ 0.003 Tc 0.149 Tw 0 -1.052 Td [(exfolia)-10 (tion,)37 ( bullae,)37 ( or an)-10 (y other severe derma)-10 (tologic reactions )]TJ /T1_2 1 Tf 0.112 Tw [([see W)17.9 (arnings )-37.3 (and)3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.052 Td (Precautions \(5.12 a)Tj (nd 5.16\)])Tj /T1_1 1 Tf 0 Tc 0 Tw (.)Tj /T1_0 1 Tf -0.017 Tc 0.017 Tw 0 -1.943 Td (3)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 3.375 0 Td (DOSAGE FORMS AND STRENGTHS)Tj /T1_1 1 Tf 0.017 Tw -3.375 -1.546 Td [(Ca)-9.8 (psules:)]TJ 1.192 -1.599 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.005 Tc 0.111 Tw 1.508 0 Td [(50 mg white,)36.7 ( printed with )37 (\223Celgene/50 mg\224)36.6 ( on the bod)-10.3 (y and a )37 (\223Do Not Get)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(Pregnant\224)37.2 ( logo on the ca)-9.8 (p.)]TJ 0.017 Tw -1.508 -1.408 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.005 Tc 0.106 Tw 1.508 0 Td [(10)0.5 (0 m)0.5 (g ta)0.5 (n,)37.4 ( pr)0.5 (int)0.5 (ed)0.5 ( w)0.5 (it)0.5 (h )36.6 (\223)0.5 (Cel)0.5 (ge)0.5 (ne/)0.5 (10)0.5 (0 m)0.5 (g\224)37.4 ( on)0.5 ( t)0.5 (he)0.5 ( bo)0.5 (d)-9.6 (y)0.5 ( a)0.5 (nd a )36.7 (\223Do)0.5 ( N)0.5 (ot Ge)0.5 (t)-5 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(Pregnant\224)37.2 ( logo on the ca)-9.8 (p.)]TJ 0.017 Tw -1.508 -1.408 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.01 Tc 0.086 Tw 1.508 0 Td [(150 mg tan bod)-10.3 (y printed with )37.1 (\223Celgene/150 mg\224)36.6 ( and blue ca)-10.3 (p printed with a)-10 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(\223Do Not Get Pregnant\224)37.2 ( logo.)]TJ 0.017 Tw -1.508 -1.408 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.008 Tc 0.092 Tw 1.508 0 Td [(200 mg blue,)37.3 ( printed with )36.8 (\223Celgene/200 mg\224)37.3 ( on the bod)-9.7 (y and a )36.7 (\223Do Not Get)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.07 Td [(Pregnant\224)37.2 ( logo on the ca)-9.8 (p.)]TJ /T1_0 1 Tf 0.017 Tw -2.7 -1.751 Td (4)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(CONTRAINDIC)18.2 (A)55.2 (TIONS)]TJ -3.375 -1.61 Td (4.1)Tj /Span<>> BDC ( )Tj EMC 3.375 0 Td [(Pregnanc)10.2 (y)]TJ /T1_1 1 Tf -0.013 Tc 0.068 Tw -3.375 -1.592 Td [(THALOMID is contraindica)-9.8 (ted in females who are pregnant.)37.2 ( )37.2 (THALOMID can cause fetal)-13 ( )]TJ -0.001 Tc 0.129 Tw 0 -1.052 Td (harm when administered to a pregnant female )Tj /T1_2 1 Tf 0.092 Tw [([see )-36.6 (Boxed W)18.1 (arning,)37 ( W)18.1 (arnings )-36.6 (and)-1 ( )]TJ ET endstream endobj 105 0 obj <>stream BT /GS0 gs /T1_0 1 Tf -0.017 Tc 0.048 Tw 8 0 0 8 36 750.2881 Tm [(HIGHLIGHTS OF PRESCRIBING INFORMA)55.2 (TION)]TJ -0.005 Tc 0.106 Tw 0 -1.197 Td [(T)0.5 (he)0.5 (s)0.5 (e hi)0.5 (g)0.5 (hl)0.5 (ig)0.5 (h)0.5 (ts)0.5 ( d)0.5 (o no)0.5 (t)0.5 ( i)0.5 (n)0.5 (c)20.4 (l)0.5 (u)0.5 (de)0.5 ( al)0.5 (l t)0.5 (h)0.5 (e i)0.5 (nf)0.5 (or)0.5 (m)0.5 (at)0.5 (i)0.5 (on)0.5 ( ne)0.5 (ed)0.5 (e)0.5 (d t)0.5 (o u)0.5 (se)0.5 ( TH)0.5 (A)0.5 (LO)0.5 (MI)0.5 (D)]TJ 0 Tc 0 Tw 5.6 0 0 5.6 283.5201 743.3721 Tm (\256)Tj 8 0 0 8 288 740.7081 Tm ( )Tj -0.017 Tc 0.048 Tw -31.5 -1.062 Td [(safely and effectively)55.2 (.)37.2 ( See full prescribing information for THALOMID)24.2 (.)]TJ 0 -1.625 Td [(THALOMID \(thalidomide\) capsules,)37.2 ( for oral use)]TJ 0 -1.242 Td [(Initial U.S.)37.2 ( Appro)-9.8 (v)16.3 (al: 1)20.2 (9)-39.8 (9)-39.8 (8)]TJ ET 0.5 w q 1 0 0 1 41 663.2962 cm 0 0 m 77.591 0 l S Q q 1 0 0 1 41 566.0562 cm 0 0 m 91.414 0 l S Q BT 8 0 0 8 52.0339 691.1562 Tm [(W)18.2 (ARNING: EMBR)18.2 (Y)20.2 (O-FET)55.2 (AL TOXICITY AND VENOUS THROMBOEMBOLISM)]TJ /T1_1 1 Tf 2.006 -1.602 Td (See full prescribing information for complete boxed warning.)Tj /T1_0 1 Tf -3.385 -1.692 Td [(EMBR)18.2 (Y)20.2 (O-FET)55.1 (AL TOXICITY)]TJ 0.017 Tw 0 -1.377 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.01 Tc 0.083 Tw 1.125 0 Td [(If THALOMID is taken during pregnanc)10.1 (y)55.2 (,)37.1 ( it can cause severe birth defects)-10 ( )]TJ -0.006 Tc 0.104 Tw 0 -1.062 Td [(or )0.5 (embr)-17.8 (yo-fetal )0.5 (death.)37.1 ( )0.5 (THALOMID )0.5 (should )0.5 (never )0.5 (be )0.5 (used )0.5 (by )0.5 (females )0.5 (who)-6 ( )]TJ -0.017 Tc 0.037 Tw 0 -1.062 Td [(are pregnant or who could be pregnant while taking the drug.)37.2 ( Even a single)-17 ( )]TJ 0.002 Tc 0.144 Tw 0 -1.062 Td [(dose [1 capsule \(regardless of strength\)] taken by a pregnant woman)2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(during her pregnanc)10.2 (y can cause severe birth defects.)]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.012 Tc 0.073 Tw 1.125 0 Td [(Pregnanc)10.2 (y must be e)10.1 (xc)20.1 (luded before start of treatment.)37.1 ( Prevent pregnanc)10.1 (y)-11.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(thereafter by the use of two reliable methods of contraception.)37.3 ( \(5.1,)37.2 ( 8.3\))]TJ 0 Tc 0.132 Tw -1.125 -1.377 Td [(THALOMID is only av)16.4 (ailable through a restricted distribution program,)37.3 ( the )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td (THALOMID REMS)Tj 0 Tc 0 Tw 5.6 0 0 5.6 93.3467 583.7602 Tm (\256)Tj -0.017 Tc 0.048 Tw 8 0 0 8 97.7303 581.0962 Tm ( program \(5.2\).)Tj -7.091 -1.692 Td (VENOUS THROMBOEMBOLISM)Tj 0.017 Tw 0 -1.378 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.006 Tc 0.106 Tw 1.125 0 Td [(Signi\037cant increased risk of deep vein thrombosis \(DVT\) and pulmona\ r)-18.3 (y)-5.9 ( )]TJ -0.017 Tc 0.06 Tw 0 -1.062 Td [(embolism \(PE\) in patients with multiple myeloma receiving THALOMID wit\ h)-17 ( )]TJ 0.048 Tw 0 -1.062 Td [(de)10.2 (xamethasone \(5.3\).)]TJ ET 1 w 4 M 36 534.536 252 167.332 re S BT 0.017 Tw 8 0 0 8 36 518.7162 Tm (-------------------------------)Tj 0.048 Tw 10.93 0 Td [(INDIC)18.2 (A)55.2 (TIONS AND USAGE)]TJ 0.022 Tw /Span<>> BDC ( )Tj EMC (------------------------------)Tj /T1_2 1 Tf 0.017 Tw -10.93 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.003 Tc 0.117 Tw 1.125 0 Td [(THALOMID in combina)-9.6 (tion with dexamethasone is indica)-9.6 (ted for the trea)-9.6 (tment of)-3 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(pa)-9.8 (tients with newly dia)-9.8 (gnosed multiple myeloma \(MM\).)37.2 ( \(1.1\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.01 Tc 0.085 Tw 1.125 0 Td [(THALOMID is indica)-10.2 (ted for the acute trea)-10.2 (tment of the cutaneous manifesta)-10.2 (tions of)-10 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(modera)-9.8 (te to severe er)-17.8 (ythema nodosum leprosum \(ENL\).)]TJ -0.014 Tc 0.062 Tw 0 -1.332 Td [(THALOMID is not indica)-9.6 (ted as monothera)-9.7 (py for such ENL trea)-9.7 (tment in the presence)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(of modera)-9.8 (te to severe neuritis.)]TJ -0.015 Tc 0.06 Tw 0 -1.332 Td [(THALOMID is also indica)-9.7 (ted as maintenance thera)-9.7 (py for prevention and suppression)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(of the cutaneous manifesta)-9.8 (tions of ENL recurrence.)37.2 ( \(1.2\))]TJ /T1_0 1 Tf 0.017 Tw -1.125 -1.602 Td (---------------------------)Tj 0.048 Tw /Span<>> BDC 9.738 0 Td ( )Tj EMC 0.024 0 Td [(DOSAGE AND ADMINISTRA)55.2 (TION)]TJ /Span<>> BDC ( )Tj EMC -0.112 Tw /Span<>> BDC 12 0 Td ( )Tj EMC (---------------------------)Tj /T1_2 1 Tf 0.017 Tw -21.762 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.006 Tc 0.167 Tw 1.125 0 Td [(MM:)36.6 ( 200 mg orally once daily)54.5 (.)36.6 ( )37.3 (The recommended dose of dexamethasone is)6 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(40 mg/day on days 1-4,)37.2 ( 9-12,)37.2 ( and 17-20 ever)-17.8 (y 28 days.)37.2 ( \(2.2\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(ENL:)37.2 ( 100 to 300 mg/day for an episode of cutaneous ENL.)]TJ 0 -1.332 Td [(Up to 400 mg/day for severe cutaneous ENL.)37.2 ( \(2.3\))]TJ /T1_0 1 Tf 0.017 Tw -1.125 -1.602 Td (--------------------------)Tj 0.048 Tw 9.291 0 Td (DOSAGE FORMS AND STRENGTHS)Tj -0.206 Tw /Span<>> BDC ( )Tj EMC (--------------------------)Tj /T1_2 1 Tf 0.048 Tw -9.291 -1.647 Td [(Ca)-9.8 (psules:)37.2 ( 50 mg,)37.2 ( 100 mg,)37.2 ( 150 mg and 200 mg.)37.2 ( \(3\))]TJ /T1_0 1 Tf 0.017 Tw 0 -1.647 Td (---------------------------------)Tj 11.731 0 Td [(CONTRAINDIC)18.2 (A)55.2 (TIONS)]TJ 8.025 0 Td (---------------------------------)Tj /T1_2 1 Tf -19.757 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(Pregnanc)20.2 (y \(Boxed )37.2 (W)18.2 (arning,)37.2 ( 4.1,)37.1 ( 5.1,)37.2 ( 5.2,)37.2 ( 8.1,)37.2 ( 17\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(Demonstra)-9.8 (ted hypersensitivity to the drug or its components \(4.2,)37.2 ( 5.16,)37.2 ( 6.2\))]TJ /T1_0 1 Tf 0.017 Tw -1.125 -1.602 Td (----------------------------)Tj 0.048 Tw 9.871 0 Td [(W)18.2 (ARNINGS AND PREC)18.2 (AUTIONS)]TJ 0.021 Tw /Span<>> BDC ( )Tj EMC (---------------------------)Tj /T1_2 1 Tf 0.017 Tw -9.871 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.004 Tc 0.151 Tw 1.125 0 Td [(I)0.5 (s)0.6 (c)0.5 (h)0.5 (e)0.6 (m)0.5 (i)0.6 (c)0.5 ( h)0.5 (e)0.6 (a)0.5 (r)0.6 (t)0.5 ( d)0.5 (i)0.6 (s)0.5 (e)0.5 (a)0.6 (s)0.5 (e)0.6 ( \()0.5 (i)0.5 (n)0.6 (c)20.5 (l)0.5 (u)0.5 (d)0.6 (i)0.5 (n)0.5 (g)0.6 ( m)0.5 (y)0.6 (o)0.5 (c)0.6 (a)0.5 (r)0.5 (d)0.6 (i)0.5 (a)0.6 (l)0.5 ( i)0.5 (n)0.5 (f)0.6 (a)0.5 (r)0.6 (c)0.5 (t)0.6 (i)0.5 (o)0.5 (n)0.6 (\))0.5 ( a)0.5 (n)0.6 (d)0.5 ( s)0.5 (t)0.6 (r)0.5 (o)0.6 (k)0.5 (e)0.6 ( h)0.5 (a)-9.5 (v)0.6 (e)0.5 ( b)0.6 (e)0.5 (e)0.5 (n)4 ( )]TJ -0.008 Tc 0.095 Tw 0 -1.062 Td [(obser)-18.1 (ved in pa)-10.1 (tients trea)-10.1 (ted with )37.2 (THALOMID in combina)-10.1 (tion with dexamethasone.)29.1 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.062 Td (\(5.3\))Tj 34.875 58.891 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.016 Tc 0.06 Tw 1.125 0 Td [(Increased Mortality:)37.2 ( Obser)-17.7 (ved in pa)-9.7 (tients with MM when pembrolizumab was added)-16 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(to dexamethasone and a thalidomide analogue.)37.2 ( \(5.4\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.015 Tc 0.06 Tw 1.125 0 Td [(Dro)-10 (wsiness and Somnolence:)36.9 ( Instruct pa)-10.1 (tients to a)-10.1 (void situa)-10.1 (tions where dro)-10 (wsiness)-15 ( )]TJ -0.009 Tc 0.09 Tw 0 -1.062 Td [(may )0.6 (be )0.6 (a )0.5 (problem )0.5 (and )0.5 (not )0.6 (to )0.6 (take )0.6 (other )0.6 (medica)-10 (tions )0.6 (tha)-10 (t )0.5 (may )0.6 (cause )0.6 (dro)-10 (wsiness.)28.1 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.062 Td (\(5.5\))Tj -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.01 Tc 0.181 Tw 1.125 0 Td [(P)18.5 (e)0.5 (ri)0.5 (p)0.5 (he)0.5 (r)0.5 (a)0.5 (l)0.5 ( N)0.5 (e)0.5 (ur)0.5 (o)0.5 (p)0.5 (a)-9.6 (t)0.5 (h)0.5 (y)0.5 (:)37.4 ( M)0.5 (on)0.5 (i)0.5 (t)0.5 (or)0.5 ( pa)-9.5 (t)0.5 (i)0.5 (e)0.5 (nt)0.5 (s)0.5 ( f)0.5 (o)0.5 (r)0.5 ( s)0.5 (i)0.5 (gn)0.5 (s)0.5 ( o)0.5 (r)0.5 ( s)0.5 (y)0.5 (m)0.5 (pt)0.5 (o)0.5 (m)0.5 (s o)0.5 (f)0.5 ( p)0.5 (e)0.5 (ri)0.5 (p)0.5 (he)0.5 (r)0.5 (a)0.5 (l)10 ( )]TJ -0.008 Tc 0.092 Tw 0 -1.062 Td [(neuropa)-9.7 (thy during trea)-9.6 (tment.)37.3 ( Discontinue )37.2 (THALOMID \(thalidomide\) if symptoms of)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(drug-induced peripheral neuropa)-9.8 (thy occur)74.2 (,)37.2 ( if c)20.2 (linically a)-9.8 (ppropria)-9.8 (te.)37.2 ( \(5.6\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.021 Tc 0.036 Tw 1.125 0 Td [(Dizziness and Orthosta)-9.9 (tic Hypotension:)37 ( )37.1 (Advise pa)-9.9 (tients to sit upright for a few minutes)-21 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(prior to standing up from a recumbent position.)37.2 ( \(5.7\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.008 Tc 0.091 Tw 1.125 0 Td [(N)0.5 (e)0.5 (ut)0.5 (r)0.5 (o)0.5 (p)0.5 (e)0.5 (ni)0.5 (a)0.5 ( a)0.5 (n)0.5 (d)0.5 ( )36.8 (T)0.5 (hr)0.5 (o)0.5 (m)0.5 (b)0.5 (o)0.5 (c)20.4 (y)0.5 (t)0.5 (o)0.5 (p)0.5 (en)0.5 (i)0.5 (a)0.5 (:)37.5 ( P)18.5 (a)-9.5 (ti)0.5 (e)0.5 (n)0.5 (t)0.5 (s)0.5 ( m)0.5 (a)0.5 (y)0.5 ( r)0.5 (eq)0.5 (u)0.5 (i)0.5 (r)0.5 (e)0.5 ( d)0.5 (o)0.5 (se)0.5 ( in)0.5 (t)0.5 (e)0.5 (r)0.5 (ru)0.5 (p)0.5 (t)0.5 (i)0.5 (o)0.5 (n a)0.5 (nd)0.5 (/)0.5 (o)0.5 (r)-8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(dose reduction.)37.2 ( \(5.8,)37.2 ( 5.9\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(Increased HIV )37.2 (Viral Load:)37.2 ( Measure viral load during trea)-9.8 (tment.)37.2 ( \(5.10\))]TJ 0.017 Tw -1.125 -1.333 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.014 Tc 0.067 Tw 1.125 0 Td [(Brad)-10.5 (ycardia:)36.5 ( Monitor pa)-10.5 (tients for brad)-10.5 (ycardia and possible syncope.)36.6 ( Dose reduction)-14 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(or discontinua)-9.8 (tion may be required.)37.2 ( \(5.11\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(Severe Cutaneous Reactions:)37.2 ( Discontinue )37.2 (THALOMID for severe reactions.)37.2 ( \(5.12\))]TJ 0.017 Tw -1.125 -1.333 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.01 Tc 0.086 Tw 1.125 0 Td [(Seizures:)36.7 ( Monitor pa)-10.3 (tients with a histor)-18.3 (y of seizures or other risk factors for acute)-9.9 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(seizure activity)55.2 (.)37.2 ( \(5.13\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.013 Tc 0.07 Tw 1.125 0 Td [(T)73.9 (umor )0.5 (L)36.9 (ysis )0.5 (Syndrome:)37 ( Monitor pa)-10.1 (tients )0.5 (a)-10.1 (t )0.5 (risk )0.5 (\(e.g.,)37 ( those )0.5 (with )0.5 (high )0.5 (tumor )0.5 (burden)-13 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(prior to trea)-9.8 (tment\) and take a)-9.8 (ppropria)-9.8 (te precautions.)37.2 ( \(5.14\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.019 Tc 0.036 Tw 1.125 0 Td [(Hypersensitivity:)37.3 ( Monitor pa)-9.7 (tients for potential hypersensitivity)55.3 (.)37.3 ( Discontinue )37.3 (THALOMID)-19 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(for angioedema and ana)-9.8 (phylaxis.)37.3 ( \(5.16\))]TJ /T1_0 1 Tf 0.017 Tw -1.125 -1.602 Td (---------------------------------)Tj 0.048 Tw 11.651 0 Td (ADVERSE REACTIONS)Tj 0.037 Tw /Span<>> BDC ( )Tj EMC (--------------------------------)Tj /T1_2 1 Tf 0.017 Tw -11.651 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.004 Tc 0.151 Tw 1.125 0 Td [(M)0.5 (M)0.5 (:)37.5 ( )37 (T)0.5 (h)0.5 (e)0.5 ( m)0.5 (o)0.5 (s)0.5 (t)0.5 ( c)0.5 (o)0.6 (m)0.5 (m)0.5 (o)0.5 (n)0.5 ( a)0.5 (d)0.5 (v)0.5 (e)0.5 (r)0.5 (s)0.5 (e)0.5 ( r)0.5 (e)0.5 (a)0.6 (c)0.5 (t)0.5 (i)0.5 (o)0.5 (n)0.5 (s)0.5 ( \()0.5 (\037)0.5 ( 2)0.5 (0)0.5 (%)0.5 (\))0.5 ( a)0.5 (r)0.5 (e)0.5 ( f)0.6 (a)-9.5 (t)0.5 (i)0.5 (g)0.5 (u)0.5 (e)0.5 (,)37.5 ( h)0.5 (y)0.5 (p)0.5 (o)0.5 (c)0.5 (a)0.5 (l)0.5 (c)0.5 (e)0.5 (m)0.6 (i)0.5 (a)0.5 (,)40.9 ( )]TJ -0.008 Tc 0.092 Tw 0 -1.062 Td [(edema,)37.3 ( constipa)-9.6 (tion,)37.3 ( neuropa)-9.6 (thy-sensor)-17.6 (y)55.4 (,)37.3 ( d)-9.6 (yspnea,)37.3 ( musc)20.4 (le weakness,)37.3 ( leukopenia,)29 ( )]TJ 0.003 Tc 0.148 Tw 0 -1.062 Td [(neutropenia,)37.2 ( rash/desquama)-9.8 (tion,)37.2 ( confusion,)37.2 ( anorexia,)37.2 ( nausea,)37.2 ( anxiety/a)-9.8 (gita)-9.8 (tion,)40.1 ( )]TJ -0.015 Tc 0.06 Tw 0 -1.062 Td [(asthenia,)37.3 ( tremor)74.2 (,)37.3 ( fever)74.3 (,)37.3 ( weight loss,)37.2 ( thrombosis/embolism,)37.3 ( neuropa)-9.8 (thy-motor)74.3 (,)37.2 ( weight)-15 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(gain,)37.2 ( dizziness,)37.2 ( and dr)-17.8 (y skin.)37.2 ( \(6.1\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.002 Tc 0.141 Tw 1.125 0 Td [(E)0.5 (N)0.5 (L)0.5 (:)37.5 ( )37 (T)0.5 (h)0.5 (e)0.5 ( m)0.5 (o)0.5 (s)0.5 (t)0.5 ( c)0.5 (o)0.5 (m)0.5 (m)0.5 (o)0.5 (n)0.5 ( a)0.5 (d)0.5 (v)0.5 (e)0.5 (r)0.5 (s)0.5 (e)0.5 ( r)0.5 (e)0.5 (a)0.5 (c)0.5 (t)0.5 (i)0.5 (o)0.5 (n)0.5 (s)0.5 ( \()0.5 (\037)0.5 ( 1)0.5 (0)0.5 (%)0.5 (\))0.5 ( a)0.5 (r)0.5 (e)0.5 ( s)0.5 (o)0.5 (m)0.5 (n)0.5 (o)0.5 (l)0.5 (e)0.5 (n)0.5 (c)0.5 (e)0.5 (,)37.5 ( r)0.5 (a)0.5 (s)0.5 (h)0.5 (,)37.5 ( a)0.5 (n)0.5 (d)2 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(headache.)37.2 ( \(6.1\))]TJ /T1_0 1 Tf 0.03 Tc 0.284 Tw -1.125 -1.49 Td [(T)74 (o report SUSPECTED ADVERSE REACTIONS or embr)-18 (yo-fetal e)10 (xposure:)30 ( )]TJ -0.003 Tc 0.121 Tw 0 -1.062 Td [(contact Celgene Corporation at 1-888-423-5436 or FD)33.6 (A at 1-800-FD)33.6 (A-1088 or)-3 ( )]TJ -0.017 Tc 0.017 Tw 0 -1.062 Td [(www)37.2 (.fda.go)-9.8 (v/medwatch.)]TJ 0 -1.647 Td (---------------------------------)Tj 0.048 Tw 11.721 0 Td [(DR)-9.8 (UG INTERACTIONS)]TJ 0.107 Tw /Span<>> BDC ( )Tj EMC (--------------------------------)Tj /T1_2 1 Tf 0.017 Tw -11.721 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.042 Tw 1.125 0 Td [(Use )0.6 (caution )0.6 (if )0.5 (other )0.5 (drugs )0.5 (which )0.5 (ha)-9.8 (ve )0.5 (seda)-9.8 (tive )0.5 (and )0.6 (hypnotic )0.6 (properties,)37.2 ( )0.5 (slo)-9.8 (w )0.6 (cardiac)-17 ( )]TJ 0.048 Tw 0 -1.062 Td [(conduction and/or cause peripheral neuropa)-9.8 (thy must be used.)37.2 ( \(7.1,)37.2 ( 7.2,)37.2 ( 7.3\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.008 Tc 0.174 Tw 1.125 0 Td [(It is not kno)-10.1 (wn whether concomitant use of hormonal contraceptives further)8 ( )]TJ -0.017 Tc 0.048 Tw 0 -1.062 Td [(increases the risk of thromboembolism with )37.2 (THALOMID.)37.2 ( \(5.15,)37.2 ( 7.4\))]TJ 0.017 Tw -1.125 -1.332 Td (\225)Tj /Span<>> BDC ( )Tj EMC -0.01 Tc 0.084 Tw 1.125 0 Td [(P)18 (a)-10 (tients taking concomitant thera)-9.9 (pies such as er)-18 (ythropoietin stimula)-10 (ting a)-10 (gents or)-9.9 ( )]TJ -0.017 Tc 0.04 Tw 0 -1.062 Td [(estrogen containing thera)-9.7 (pies may ha)-9.8 (ve an increased risk of thromboembolism.)37.2 ( \(7.7\))]TJ /T1_0 1 Tf 0.017 Tw -1.125 -1.602 Td (---------------------------)Tj 0.048 Tw 9.838 0 Td [(USE IN SPECIFIC POPULA)55.2 (TIONS)]TJ -0.012 Tw /Span<>> BDC ( )Tj EMC (---------------------------)Tj /T1_2 1 Tf 0.017 Tw -9.838 -1.602 Td (\225)Tj /Span<>> BDC ( )Tj EMC 0.048 Tw 1.125 0 Td [(Lacta)-9.8 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