Sildenafil - A review of its use in erectile dysfunction

Sildenafil is an oral therapy for erectile dysfunction of a broad range of causes. By selectively inhibiting phosphodiesterase type 5, it allows corpu s' cavernosum smooth muscle to relax, potentiating erections during sexual stimulation. Blood pressure is reduced transiently by sildenafil, but more marked hypotension may occur during concurrent administration of sildenafil and organic nitrates; this combination is contraindicated. Sildenafil is rapidly absorbed, with dose-proportional peak plasma concentr ations within 1 hour of administration, The elimination half-life is 3 to 5 hours. Dosages usually begin at 50mg taken when needed approximate to 1 ho ur before sexual activity no more than once daily. The maximum dose is 100m g when needed once daily and lower doses (e,g, 25mg) may be used in elderly patients and those with hepatic or renal impairment or receiving cytochrom e P450 enzyme CYP3A4 inhibitors, such as ritonavir, saquinavir, ketoconazol e, erythromycin or cimetidine. More than 3000 patients with erectile dysfunction of organic (e,g, diabetes or spinal cord injury), psychogenic or mixed origin received sildenafil 5 to 100mg or placebo in fixed- or titrated-dose trials, Sildenafil was assoc iated with dose-related improvements in the frequency, hardness and duratio n of erections and in patients' abilities to achieve and maintain erections adequate for successful sexual intercourse. In titrated-dose trials, the m ost commonly effective doses were 50 or 100mg, although lower doses were ef fective in some patients, Sildenafil was significantly more effective than placebo in erectile dysfunction of all tested causes, The efficacy of sildenafil was not affected by patient age (> or less than or equal to 65 years) or by antihypertensive or antidepressant medications, The drug was effective in patients with severe erectile dysfunction, Effic acy was maintained in long term (l-year) studies, Sildenafil also appears t o improve the quality of life of both patients and their sexual partners. C ommon adverse events associated with sildenafil were transient and mild or moderate and included headache, flushing, dyspepsia, nasal congestion and a bnormal vision. Tolerability was maintained in long term (II year) studies. No serious sildenafil-related adverse events occurred in clinical trials; cardiovascular events seen in postmarketing surveillance generally occurred in patients with other known risk factors. Conclusions: Sildenafil is an effective oral treatment in men with erectile dysfunction. It was significantly superior to placebo in improving erectio ns and allowing successful penetrative sexual intercourse. Although its pla ce in disease management is still emerging and there are contraindications to its use, if preliminary positive reports are confirmed, sildenafil will be the pre-eminent first-line therapy for erectile dysfunction.