ࡱ>  Ebjbj 7rr:LL8L3R\ j&!&!&!f"f"f"QQQQQQQ$TAW4Qf"f"f"f"f"Q&!&!@Qx)x)x)f"&!&!Qx)f"Qx)x)PCE&! 5.0 mEq/L Serum creatinine > 2.5 mg/dL in men or > 2.0 mg/dL in women (or estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) (Class III Recommendation [Harm]; Level of Evidence B)1 a Eplerenone is available via the nonformulary process. Eplerenone may be considered in a patient with intolerance to spironolactone (e.g., gynecomastia: 9% spironolactone2, 0.5% eplerenone4; breast pain: 2% spironolactone2, 0.8% eplerenone5). It should be noted that gynecomastia is potentially reversible with discontinuation of the medication if present for less than one year, but generally irreversible if present for over 1 year; providers should regularly question their patients about breast tenderness or enlargement while taking spironolactone and switch to eplerenone if this adverse events occurs b It is unclear whether other patients with HFrEF (e.g., those with a LVEF 35-40%) will achieve similar benefit from a mineralocorticoid receptor antagonist; however, the data are suggestive, given the consistency of benefit from the clinical trials Safety Common, and potentially serious, adverse effects with the mineralocorticoid receptor antagonists include the development of hyperkalemia, especially in patients with impaired kidney function and/or who are receiving a potassium supplements or other medications with the potential to increase serum potassium (e.g., angiotensin-converting enzyme inhibitors [ACEIs], angiotensin II receptor antagonists, potassium-sparing diuretics). The risk vs. benefit of using a mineralocorticoid receptor antagonist, or modification of existing therapy to provide optimal patient outcomes while minimizing the potential for harm, in these patients needs to be determined on a case by case basis. Monitoring of potassium and kidney function will vary depending on individual patient characteristics (refer to Note below); the following recommendations are per the respective prescribing information: Eplerenone: measure potassium at baseline, within 1 week, and at 4 weeks after starting treatment, and periodically thereafter. Additional monitoring should be dictated by patient characteristics and potassium levels5 Spironolactone: measure potassium and creatinine 1 week after initiating therapy or dose increase, every 4 weeks for the first 3 months, every 3 months for 1 year, then every 6 months thereafter6 Note: 2013 ACCF/AHA HF Guideline recommends initial monitoring earlier than 1 week (e.g., within 2 to 3 days, then again at 7 days), then at least monthly for the first 3 months and then every 3 months.1 Monitoring earlier than 1 week may be prudent, especially in patients at higher risk for developing hyperkalemia (e.g., baseline potassium > 4.2mEq/L, serum creatinine > 1.6 mg/dl, on medications that may increase the risk for hyperkalemia, or with higher doses of a mineralocorticoid receptor antagonist7), or in patients with conditions that may contribute to dehydration.1 Although the incidence of serious hyperkalemia was not significantly different in patients treated with spironolactone compared to placebo in the Randomized Aldactone Evaluation Study (RALES), it is important to note that patients with serum creatinine > 2.5 mg/dL and serum potassium > 5.0 mEq/L were excluded, and patients were not taking other potassium-sparing diuretics unless hypokalemia developed.2 Serious hyperkalemia (> 6.0 mEq/L) occurred significantly more frequently with eplerenone compared to placebo in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy Survival Study (EPHESUS), and a potassium > 5.5 mEq/L was reported more frequently with eplerenone in the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF); however, doses were titrated to 50 mg as part of the protocol of these trials. As in RALES, both EMPHASIS-HF and EPHESUS excluded patients with serum creatinine > 2.5 mg/dL (or estimated glomerular filtration rate [eGFR] < 30mL/min/1.73 m2 in EMPHASIS-HF), serum potassium > 5.0 mEq/L, or use of potassium-sparing diuretics.2-4 It is also important to note that patients were closely monitored as part of the clinical trial protocols. In clinical practice, reports of discontinuations due to hyperkalemia appear to be higher than seen in the clinical trials.8-12 Hyperkalemia with a mineralocorticoid receptor antagonist occurs more frequently in patients receiving potassium supplements and in patients with kidney impairment. Concomitant use of potassium supplements or potassium-sparing diuretics with a mineralocorticoid receptor antagonist should be avoided unless hypokalemia develops. In general, potassium supplements or potassium-sparing diuretics should be discontinued when therapy with a mineralocorticoid receptor antagonist is initiated. A mineralocorticoid receptor antagonist should also be used with caution in patients with a higher baseline potassium (e.g., > 4.2mEq/L), elevated serum creatinine (e.g., > 1.6 mg/dl), or receiving ACEIs7, angiotensin II receptor antagonists, or other medications that may increase the risk for hyperkalemia (e.g., cyclosporine, tacrolimus, nonsteroidal anti-inflammatory agents). Potassium should be monitored closely in these patients with follow-up evaluation of electrolytes and kidney function after initiation and dose adjustments. More frequent monitoring may be indicated in patients on concomitant medications that may contribute to increased potassium levels, with kidney impairment or diabetes mellitus, who are of advanced age, or experiencing worsening HF or conditions that may contribute to dehydration. Patient education should be provided to avoid potassium salt substitutes, foods high in potassium, or the use of nonsteroidal anti-inflammatory agents, as indicated. In addition to hyperkalemia, mineralocorticoid receptor antagonists may cause gynecomastia, gastrointestinal side effects, and menstrual irregularities. Gynecomastia or breast pain was reported in 10% of male patients receiving spironolactone in a clinical trial in patients with HF.2 It is also noted that eplerenone should not be used in patients on concomitant therapy with a strong CYP 3A4 inhibitor (e.g., ketoconazole, itraconazole, nefazadone, clarithromycin, ritonavir, and nelfinavir). Dosing Recommendations SpironolactoneEplerenoneInitial Dose12.5 mg to 25 mg once daily (12.5 mg daily or every other day if eGFR < 50 to 30 mL/min/1.73 m2)125 mg once daily (25 mg every other day if eGFR < 50 to 30 mL/min/1.73 m2)1Maximum DoseIncrease to 25 or 50 mg once daily, as indicated in patients with worsening signs or symptoms of HF and who do not have hyperkalemiaaTitrate to 50 mg once daily, as tolerated and in patients who do not have hyperkalemiaaa serum potassium should be monitored carefully with dose increases References Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013;128:e240-e327. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure: Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999;341:709-17. Zannad F, McMurray JJV, Krum H, et al., for the EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure with mild symptoms. N Engl J Med published online Nov 14, 2010; doi:10.1056/NEJMa1009492 Pitt B, Remme W, Zannad F, et al, for the Eplerenone Post-Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003;348:1309-21. Inspra (eplerenone) prescribing information. New York, NY: Pfizer, Inc.; 2008 Apr. Aldactone (spironolactone) prescribing information. New York, NY: Pfizer, Inc.; 2008 Jan. The RALES Investigators. Effectiveness of spironolactone added to an angiotensin-converting enzyme inhibitor and a loop diuretic for severe chronic congestive heart failure (The Randomized Aldactone Evaluation Study [RALES]). Am J Cardiol 1996;78:902-7.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tamirisa+KP%22%5BAuthor%5D" \o "Click to search for citations by this author." Tamirisa KP,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Aaronson+KD%22%5BAuthor%5D" \o "Click to search for citations by this author." Aaronson KD,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Koelling+TM%22%5BAuthor%5D" \o "Click to search for citations by this author." Koelling TM. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.  HYPERLINK "javascript:AL_get(this,%20'jour',%20'Am%20Heart%20J.');" Am Heart J 2004;148:971-8.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Sligl+W%22%5BAuthor%5D" \o "Click to search for citations by this author." Sligl W,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McAlister+FA%22%5BAuthor%5D" \o "Click to search for citations by this author." McAlister FA,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Ezekowitz+J%22%5BAuthor%5D" \o "Click to search for citations by this author." Ezekowitz J,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Armstrong+PW%22%5BAuthor%5D" \o "Click to search for citations by this author." Armstrong PW. Usefulness of spironolactone in a specialized heart failure clinic.  HYPERLINK "javascript:AL_get(this,%20'jour',%20'Am%20J%20Cardiol.');" Am J Cardiol 2004;94:443-7.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Svensson+M%22%5BAuthor%5D" \o "Click to search for citations by this author." Svensson M,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Gustafsson+F%22%5BAuthor%5D" \o "Click to search for citations by this author." Gustafsson F,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Galatius+S%22%5BAuthor%5D" \o "Click to search for citations by this author." Galatius S,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hildebrandt+PR%22%5BAuthor%5D" \o "Click to search for citations by this author." Hildebrandt PR,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Atar+D%22%5BAuthor%5D" \o "Click to search for citations by this author." Atar D. How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure?  HYPERLINK "javascript:AL_get(this,%20'jour',%20'J%20Card%20Fail.');" J Card Fail 2004;10:297-303.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Bozkurt+B%22%5BAuthor%5D" \o "Click to search for citations by this author." Bozkurt B,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Agoston+I%22%5BAuthor%5D" \o "Click to search for citations by this author." Agoston I,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Knowlton+AA%22%5BAuthor%5D" \o "Click to search for citations by this author." Knowlton AA. Complications of inappropriate use of spironolactone in heart failure: when an old medicine spirals out of new guidelines.  HYPERLINK "javascript:AL_get(this,%20'jour',%20'J%20Am%20Coll%20Cardiol.');" J Am Coll Cardiol 2003;41:211-4.  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Juurlink+DN%22%5BAuthor%5D" \o "Click to search for citations by this author." Juurlink DN,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Mamdani+MM%22%5BAuthor%5D" \o "Click to search for citations by this author." Mamdani MM,  HYPERLINK "http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lee+DS%22%5BAuthor%5D" \o "Click to search for citations by this author." Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.  HYPERLINK "javascript:AL_get(this,%20'jour',%20'N%20Engl%20J%20Med.');" N Engl J Med 2004;351:543-51. Prepared (November 2010; Updated July 2014)/Contact Person: Elaine M. Furmaga, Pharm.D, National PBM Clinical Pharmacy Program Manager, VA National PBM Services     Recommendations for Use: Mineralocorticoid Receptor Antagonists in HFrEF PAGE  January 2011; Updated July 2014 Updated versions may be found at  HYPERLINK "http://www.pbm.va.gov" www.pbm.va.gov or  HYPERLINK "http://vaww.pbm.va.gov" http://vaww.pbm.va.gov  PAGE \* MERGEFORMAT 2 Recommendations for Use: Mineralocorticoid Receptor Antagonists in HFrEF January 2011; Updated July 2014 Updated versions may be found at  HYPERLINK "http://www.pbm.va.gov" www.pbm.va.gov or  HYPERLINK "https://vaww.cmopnational.va.gov/cmop/PBM/default.aspx" https://vaww.cmopnational.va.gov/cmop/PBM/default.aspx '(,CDE`a  еЩБtbQ?#h5)hV^5CJOJQJ^JaJ hBi5>*CJOJQJ^JaJ#h@hBi6CJOJQJ^JaJ&h@hBi6CJOJQJ]^JaJhBi5CJ\hBiCJOJQJ^Jh`CJOJQJ^JhhCJOJQJ^Jh])hBiCJOJQJ^JhfpeCJOJQJ^JhBiCJOJQJ^JhY(=CJOJQJ^JhgnCJOJQJ^Jh+[CJOJQJ^J(a 1$ & F h^hgdvgdE' h^h`gdY(= & F h^hgd@ & F h^hgdY(=gdJ*gd.gdBi!$$d&d-DM NPa$gdBi    ! 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