Clinical Monograph for Drug Formulary Review: Erectile Dysfunction Agents

BACKGROUND: Significant advances in the pharmacologic treatment of erectile dysfunction (ERD) have occurred in recent years, most notably the introduction of sildenafil, the first oral selective phosphodiesterase type 5 (PDE5) inhibitor, in 1998. Sildenafil quickly gained acceptance by the medical community and the public because of its broad efficacy for different types of ERD and its ease of use. Two PDE5 inhibitors, vardenafil and tadalafil, have since joined sildenafil to compete in the ERD market. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used ERD drugs as part of drug formulary management process and decision making by the Pharmacy and Therapeutics (P&T) committee. OBJECTIVES: To provide readers with a comprehensive clinical monograph on ERD drugs written from a managed care perspective. METHODS: The PBM clinical monograph is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (Up-to-Date online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs prepared by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: Despite the lack of head-to-head comparative studies, all 3 PDE5 inhibitors appear to have equivalent efficacy in the treatment of general ERD and ERD associated with diabetes and post-prostatectomy. Sildenafil has additional efficacy data in the management of ERD associated with spinal cord injury and antidepressant medications. Tadalafil has the longest duration of action (up to 36 hours); this feature can be both beneficial (greater sexual spontaneity) or possibly detrimental (greater exposure to drug, delayed adverse events). All 3 PDE5 inhibitors appear to be generally well tolerated and have similar contraindications and warnings. However, vardenafil is the only PDE5 inhibitor with a cardiac conduction precaution. Alprostadil products are recommended in current ERD guidelines as second-line therapy for those who have not responded or cannot take the oral PDE5 inhibitors. Overall, higher clinical efficacy rates are achieved with intracavernous than with transurethral administration. CONCLUSIONS: A large amount of clinical efficacy and safety data has been published since the market launch of sildenafil in 1998. Sildenafil has the greatest body of efficacy and safety evidence. No comparative studies have been conducted with any of the PDE5 inhibitors. Differences in study populations, primary end points, and measurement tools make comparisons difficult. However, all PDE5 inhibitors appear to be roughly equivalent in efficacy, with minor differences in adverse event profiles. Until more comparative data are available, economic considerations will be a significant factor in choosing ERD products for formulary inclusion.