FDA has approved sildenafil, the first oral tablet to treat erectile dysfunction (ED). Taken about an hour before anticipated sexual activity, sildenafil enhances the response to sexual stimulation. It led to at least some improvement in 7 out of 10 men with ED compared with 2 out of 10 who improved on placebo. In clinical studies, sildenafil was assessed for its effect on the ability of men with ED to engage in sexual activity and in many cases specifically on their ability to achieve and maintain an erection sufficient for satisfactory sexual activity. It was evaluated primarily at doses of 25 mg, 50 mg, and 100 mg in 21 randomized, double-blind, placebo-controlled trials of up to 6 months in duration. Sildenafil was administered to more than 3,000 patients aged 19 to 87 years, with ED of various etiologies (organic, psychogenic, mixed) with a mean duration of 5 years. The drug demonstrated statistically significant improvement compared with placebo in all 21 studies.
The first in a new class of medications, sildenafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Physiologically, sexual stimulation causes local release of nitric oxide (NO) in the corpus caver-nosum. NO then activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil enhances the effect of NO by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum.
Sildenafil was effective in a broad range of ED patients, including those whose ED arose from diabetes mellitus, spinal cord injury, transurethral resection of the prostate, or no known physical cause. It was used in patients with a history of coronary artery disease, hypertension, peripheral vascular disease, depression, or coronary artery bypass graft, and in patients taking various drugs, including antidepressants/antipsychotics and antihypertensives/diuretics.
For most patients, the recommended dose is 50 mg, taken as needed approximately 1 hour before sexual activity. However, the drug may be taken anywhere from one-half hour to 4 hours before sexual activity. Based on effectiveness and toleration, the dose may be increased to a maximum recommended dose of 100 mg or decreased to 25 mg. The maximum recommended dosing frequency is once a day. Sildenafil was shown to potentiate the hypotensive effects of nitrates, and its administration in patients who use various nitrates in any form is therefore contraindicated.
Sildenafil’s side effects, when they occur, are usually mild and temporary. The most common side effects reported in clinical trials included headache, flushing, and upset stomach. Visual changes, such as mild and temporary changes in blue/green color perception or increased sensitivity to light, can occur.
A thorough medical history and physical examination should be undertaken to diagnose ED, determine potential underlying causes, and identify appropriate treatment.There is a degree of cardiac risk associated with sexual activity; therefore, physicians may wish to consider the cardiovascular status of their patients prior to initiating any treatment for ED.
Sildenafil is manufactured by Pfizer Pharmaceuticals, New York, NY, and marketed under the trade name Viagra. The company reported to FDA on May 21, 1998, that it learned of the deaths of six people who had taken sildenafil. FDA is investigating these reports and will continue to monitor any other serious adverse event reports to determine if any changes exist in this drug’s safety profile. The label states that Viagra and the concomitant administration of nitroglycerin or other organic nitrates is contraindicated.