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The FDA has approved Pfizer's eplerenone (Inspra) for the treatment of congestive heart failure (CHF) in patients who have sustained a myocardial infarction. The drug is a selective aldosterone blocker, a new class of drug for the treatment of CHF. It differs from spironolactone in that it selectively blocks the mineralocorticoid receptor, but not the glucocorticoid, progesterone, or androgen receptors. The approval of eplerenone for the treatment of CHF was based primarily on the findings of the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), which was published in the April 2003 issue of the New England Journal of Medicine. In EPHESUS, nearly 7000 patients with acute myocardial infarction and left ventricular dysfunction and heart failure were randomized to eplerenone 25 mg per day titrated up to 50 mg per day or placebo. Both groups also received optimal medical therapy. Following 16 months of follow-up, there was a significant reduction in death rate (RR, 0.85; 95% CI, 0.75-0.96; P = 0.008) in the eplerenone group. The drug also resulted in significant reductions in cardiovascular deaths and sudden cardiac death (N Engl J Med. 2003;348:1309-1321). The drug appears to be well tolerated with the primary adverse events being hyperkalemia and increased creatinine levels. Because of the selectivity of the drug for the mineralocorticoid receptor, there is no reported increase in menstrual disorders, gynecomastia, or impotence with eplerenone, adverse reactions that are frequently associated with spironolactone usage. Pfizer will make the drug available through an early access program by December 2003. Eplerenone was previously approved for treatment of hypertension alone or in combination with other antihypertensive agents.
No Adverse Effect with Concomitant Aspirin and ACE Inhibitor Use in CHF Patients
Aspirin does not adversely affect survival in patients with stable CHF who were being treated with an ACE inhibitor, according to a French study published in October. This study contradicts earlier studies, which raised concern about the concomitant use of aspirin and ACE inhibitors in CHF patients. In a retrospective analysis, 755 stable patients with left ventricular systolic dysfunction were followed for nearly 5.5 years. Most patients were on an ACE inhibitor and 317 were on aspirin, the majority on low-dose aspirin (< 200 mg/d). End points included cardiac-related deaths, version transplants, nonurgent transplants, and noncardiac deaths. The analysis revealed no relationship between the use of aspirin and survival among patients taking ACE inhibitors. Brunner-La Rocca and colleagues conclude that aspirin is not harmful for heart failure patients who are taking ACE inhibitors (Chest. 2003; 124:1192-1194, editorial 1250-1258).
HIV Treatment Shows High Failure Rate
A once-daily, triple nucleoside reverse transcriptase inhibitor (NRTI) HIV treatment regimen has seen a high number of treatment failures and HIV resistance. The rate of virologic failure reached 91% along with a high rate of HIV resistance to NRTIs in treatment-naive patients. Gilead Sciences has taken the step of notifying health-care professionals to discontinue the regimen in a "Dear Doctor" letter. The treatment failures were seen with a regimen containing didanosine enteric-coated beadlets (Videx EC, Bristol-Myers Squibb), lamivudine (Epivir, GlaxoSmithKline), and tenofovir disoproxil fumarate (Viread, Gilead) in HIV-infected treatment-naive patients. Tenovir DF is no longer recommended for use in combination with didanosine and lamivudine in treatment-naive or experienced patients with HIV infections. The FDA is also recommending that patients currently on this regimen should be considered for treatment modification (www.fda.gov/medwatch/SAFETY/2003/safety03.htm#viread [Accessed Nov. 5, 2003]).
New Psoriasis Treatment Approved
The FDA has approved the second biologic for the treatment of psoriasis. Genentech’s efalizumab (Raptiva) was approved for the treatment of moderate-to-severe psoriasis in October. It joins Biogen’s alefacept (Amevive), which was approved in January 2003 and will probably soon be joined by Amgen’s rheumatoid arthritis drug etanercept (Enbrel), which is also seeking approval for the treatment of psoriasis. Efalizumab is a humanized therapeutic antibody that blocks the activation, reactivation, and trafficking of T-cells that lead to the development of psoriasis symptoms. The drug requires a once-a-week self-injection and will cost $14,000 a year.
THG Controversy Gains Steam
The FDA has issued a warning regarding tetrahydrogestrinone (THG), a synthetic "designer" steroid, which is derived by simple chemical modifications from another anabolic steroid. Little is known about the safety of the drug or its structure, but its relationship to better-known products suggests that it may represent a considerable health risk. THG has been marketed as a dietary supplement; however, the FDA has determined that it is an unapproved drug and as such cannot be legally marketed. Urine assays have recently been developed for THG, and testing of athletes has revealed some disturbing findings. Four US Olympic athletes, as well as Britain’s leading sprinter, have tested positive in the initial assay—further tests are to follow. A San Francisco grand jury is looking into a California nutritional supplement manufacturer that may be the source of the drug. The FDA statement is available at www.fda.gov/bbs/topics/NEWS/2003/NEW00967.html (accessed Nov. 5, 2003).
New Study Examines Sulfonamide Nonantibiotics
Is it safe to use a sulfonamide-based nonantibiotic in patients who have an allergy to sulfonamide antibiotics? A large retrospective cohort study from the United Kingdom looked at this issue and suggests that penicillin allergy is as likely or more likely to be associated with nonantibiotic sulfonamide reactions as a history of sulfonamide antibiotics allergy. Nearly 10% of patients with a history of allergy to a sulfonamide antibiotic had an allergic reaction after receiving a sulfonamide nonantibiotic compared to only 1.6% of patients who have no history of allergy to sulfonamide antibiotics. Patients who had a history of hypersensitivity to penicillin were most likely to have an allergic reaction to a sulfonamide nonantibiotic (adjusted odds ratio, 0.6; 95% CI, 0.5-0.8). Strom and associates conclude that there is a relationship between hypersensitivity to sulfonamide antibiotics and subsequent allergic reaction with sulfonamide nonantibiotics such as thiazide diuretics; however, this risk seems to be due to a predisposition to allergic reactions rather than a cross reactivity between sulfonamide-based drugs (N Engl J Med. 2003;349:1628-1635).
FDA Actions
Novavax Inc has received FDA approval to market a new topical estrogen therapy for the treatment of hot flashes in menopausal women. The white lotion is an emulsion of estradiol topical that women apply only to their legs, thighs or calves on a daily basis. The topical preparation is absorbed through the skin allowing estradiol to bypass enterohepatic circulation. Estradiol topical emulsion will be marketed under the trade name Estrasorb.
The FDA has issued an approvable letter to Cephalon, Inc. regarding expanded indications for modafinil (Provigil). The drug is currently approved for excessive daytime sleepiness associated with narcolepsy. The letter states that modafinil is approvable for improving wakefulness in patients with excessive sleepiness associated with shiftwork and in patients with obstructive sleep apnea/hypopnea syndrome. Cephalon had also sought approval for other causes of excessive sleepiness including jet lag; however, the FDA panel could not come to agreement on that recommendation.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Telephone: (404) 262-5517. E-mail: [email protected]. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.
The FDA has approved Pfizer's eplerenone (Inspra) for the treatment of congestive heart failure (CHF) in patients who have sustained a myocardial infarction.
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