Sildenafil is the first oral drug approved by the U.S. Food and Drug Administration for treatment of erectile dysfunction. Although other drugs have been on the market for some time, they have met with mixed success because of the need for injection or insertion into the urethra. Sildenafil enhances the physiologic response that causes penile erection after sexual arousal. It inhibits the enzyme conversion that produces the contraction of the smooth muscle of the corpus cavernosum, allowing engorgement to be maintained. Medical Letter consultants reviewed the data on this drug.
Plasma concentrations of sildenafil reach a peak in about one hour. A fatty meal delays the peak by about one hour and decreases the peak concentration without affecting total absorption. The drug is actively metabolized in the liver and is excreted largely as metabolites in the stool. Both the parent drug and the active metabolite have a half-life of about four hours. In men older than 65 years and in men with hepatic or severe renal insufficiency, clearance is slower.
Only one published study of sildenafil using objective measurements has been conducted. Plethysmographic measurements were obtained in 12 men with erectile dysfunction in a randomized, controlled crossover study. The mean duration of erections was about one minute with placebo, four minutes with 10 mg of sildenafil, about eight minutes with 25 mg and eight to 11 minutes with 50 mg of active drug. The men were instructed to record erectile activity after taking 25 mg of sildenafil or placebo once daily for seven days. The number of erections within two hours after taking sildenafil was about five times greater with the active drug than with placebo.
Other unpublished studies evaluated men with erectile dysfunction who took 25, 50 or 100 mg of sildenafil or placebo at home for up to six months. The drug did not affect the frequency of attempted intercourse. However, in four fixed-dose trials, improvement in erections was reported by 63 percent of the 214 men taking 25 mg of sildenafil, 74 percent of the 391 men taking 50 mg and 82 percent of the 380 men taking 100 mg of the drug. Twenty-four percent of the 463 men taking placebo experienced improvement in erectile functioning. The effect was detectable as soon as 30 minutes after taking the drug and lasted up to four hours. Some men also reported increased erectile functioning the next day. Forty-three percent of men with radical prostatectomy reported improvement in erections after taking sildenafil compared with 15 percent after taking placebo.
Sildenafil lowers blood pressure slightly in normal patients and substantially in patients who are undergoing nitrate therapy for angina. The most common side effects are headache, flushing and dyspepsia. Transient abnormal vision, usually a color tinge or increased sensitivity to light, is uncommon and is usually dose-related. No incidence of priapism has been reported. Sildenafil should be used cautiously in patients taking cimetidine, erythromycin, rifampin and ketoconazole.
Sildenafil is available in 25-, 50- and 100-mg tablets. The manufacturer recommends an initial dosage of 50 mg (which can be increased to 100 mg if necessary) taken one hour before intercourse. Patients older than 65 years of age, those with hepatic or renal dysfunction and those who are taking a CYP3A4 inhibitor should start with a 25-mg dosage. Sildenafil should not be taken more than once a day. The cost to the pharmacist for 30 tablets of any size is about $263.
Medical Letter consultants conclude that sildenafil appears to be an effective oral drug for treatment of erectile dysfunction, although not all patients respond, and long-term safety has not been established. The hypotensive effects may be troublesome in some patients; persons using nitrates for treatment of angina should not take sildenafil.