Vardenafil An oral selective phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction

Erectile dysfunction (ED) is defined as the inability to attain and/or maintain penile erection sufficient for satisfactory sexual performance.1 The Massachusetts Male Aging Study, a cross-sectional, community-based, random-sample survey, suggests that 10 million to 30 million men in the United States suffer from ED, with more than 900,000 estimated new cases annually.2 A higher prevalence of ED has been identified in men older than 65 years of age (5% at age 40; 25% at age 65) and in men with chronic diseases such as diabetes mellitus, hypertension, and/or vascular disease.2,3 A number of FDA-approved treatment modalities exist for the treatment of ED, including penile protheses, intrauretheral suppositories (MUSE, Vivus) or intracavernosal injection of alprostadil (Caverject, Pharmacia), vacuum devices, and, more recently, orally administered agents such as sublingual apomorphine (Uprima, Abbott) and selective phosphodiesterase (PDE) type 5 inhibitors.4 Since its release in 1998, sildenafil (Viagra, Pfizer), the first PDE5 inhibitor to reach the US market, has become the treatment of choice for ED due to its efficacy, safety, and tolerability compared to earlier ED treatments.4 Despite clinical data supporting its safety and tolerability, sildenafil is not without some troublesome adverse effects.5 Post-marketing data show that sildenafil has been associated with more than 500 deaths, many due to myocardial infarction and arrhythmia.6,7 Sildenafil has also been associated with an 11% incidence of visual disturbances, characterized as altered color-vision perception.8 Despite sildenafil’s overwhelming marketing success,9 the occurrence of cardiac and ocular adverse effects has prompted the ongoing development of new PDE5 inhibitors, which are hoped to have similar efficacy and a lower incidence of adverse effects. Another PDE5 inhibitor, tadalafil (Cialis, Lilly/ICOS) received FDA approval for marketing in the US and should be available sometime in 2003 (see June 2002 “Focus on,” page 289). In September 2001, Bayer AG submitted a new drug application for vardenafil (Levitra) to the FDA.10 If approved, vardenafil will be the third PDE5 inhibitor to reach the US market and the fourth oral agent to gain FDA approval for treatment of ED. ■Abstract Vardenafil (Levitra, Bayer AG/GlaxoSmithKline) is a selective inhibitor of phosphodiesterase 5 (PDE5) currently under review by FDA for the treatment of erectile dysfunction (ED). If approved, vardenafil will become the third PDE5 inhibitor to be marketed in the United States and the fourth oral agent approved for the treatment of ED. Vardenafil has been studied in subjects of various ages (<45 and >65 years of age), with different etiologies and different baseline severity of ED. Studies evaluating vardenafil have determined it to be safe and effective at doses of 5 mg to 40 mg, including subjects with diabetes mellitus and subjects who have undergone radical prostatectomy. Vardenafil has a pharmacokinetic profile similar to that of sildenafil (Viagra, Pfizer), with an onset of action and half-life of 0.7 hours and 5 hours, respectively. Vardenafil, like other PDE5 inhibitors, is metabolized hepatically via the cytochrome P-450 system. The drug appears to be well tolerated. In clinical trials, headache, dyspepsia, and flushing were the most common adverse effects reported by subjects taking vardenafil. No adverse hemodynamic or visual effects have been reported during clinical trials of vardenafil; however, further investigation, including post-marketing surveillance, will be required to determine whether vardenafil will cause these adverse effects. In vivo, vardenafil has been found not to interact with nifedipine, nitroglycerin, digoxin, magnesium hydroxide/aluminum oxide, or ranitidine. Only a small, clinically insignificant interaction was observed when vardenafil was given concurrently with cimetidine. Further research and clinical experience with the newer PDE5 inhibitors (vardenafil and tadalafil [Cialis, Lilly/ICOS]) will be needed before their roles in the treatment of ED can be determined. (Formulary 2003;38:131–48.)