Sildenafil citrate (Viagra ®)

The results of treatment with Viagra ® were reported recently in a comprehensive paper that gave an account of two studies (9). The first, which was double-blind, described the results in men who were randomly assigned to treatment with placebo (216 men), or 25 mg (96), 50 mg (105), or 100 mg (101) of Viagra ®, taken one hour before they planned to have sex (and not more than once daily). The men who were studied had impotence of organic, psychological, or mixed origin. Men with anatomical defects of the penis, another sexual disorder, spinal cord injury, major psychiatric disorder, poorly controlled diabetes, or stroke, or a heart attack within six months, or treatment with organic nitrates, were excluded.

The mean age was 58 years. About 80% of the subjects had organic causes for an average of 3 years, and about 28% had hypertension, 18% hyperlipidaemia, 14% diabetes, 11% radical prostatectomy and 8% ischaemic heart disease. Efficacy of treatment was assessed from the answers to the questions "When you attempted sexual intercourse, how often were you able to penetrate your partner?" and "During sexual intercourse, how often were you able to maintain an erection after you had penetrated your partner?"

With doses of 50 and 100 mg there was a change from erections that were rarely adequate for penetration and rarely maintained to erections that were both adequate and maintained about 75% of the time. Effectiveness was broadly similar for men whose impotence had an organic, psychological or mixed cause.

The second study, which was also double blind, involved 329 different men who were randomly assigned to treatment with placebo (160 men) or 50 mg of Viagra® (163 men) for 12 weeks. At follow-up visits the dose was doubled, or reduced by 50%, on the basis of effectiveness and adverse effects. The mean number of successful attempts at sexual intercourse during the last four weeks of treatment was 5.9 with Viagra®, compared with 1.5 with placebo. Successful sexual intercourse occurred in 69% of attempts with Viagra ® and 22% with placebo. Improved erections were reported by 101 of 136 men taking Viagra ® and 23 of 118 taking placebo. There was no change reported in the level of sexual desire.

In the UK, the recommended dose is 50 mg. In older men, or those with cardiovascular or renal disease, the recommended starting dose is 25 mg.

Adverse effects

The main adverse effects reported in the paper were flushing, headache, dyspepsia, visual disturbance (changes in perception of color hue or brightness) and rhinitis. These were mild, and the number of discontinuations because of adverse effects was small at 5 of 479 patients (<1%). There were no cases of priapism (painful or uncomfortable erection persisting for several hours after ejaculation) in these studies.

A more complete picture of adverse events comes from an analysis of all randomized and double blind placebo-controlled studies, together with open-label extensions (10). The Table below, taken from reference 10, provides information on the 1500 men given Viagra ® or placebo in flexible-dose studies, those most likely to reflect drug use in clinical practice. Over 90% of adverse effects were mild or moderate, and discontinuations of treatment because of adverse effects in these studies were just over 2% for both placebo and Viagra ®. Though there were no cases of priapism in this study, there have recently been six cases of priapism recorded. It is likely that the risk of this is dose-related.

Because men prescribed Viagra ® may well have cardiovascular risk factors, such as hypertension, hyperlipidaemia and diabetes, any effect of the drug on cardiovascular events is very important. An analysis of all 18 placebo-controlled trials detected no difference in the incidence of myocardial infarction, angina or coronary artery disorders between men treated with Viagra ® and those taking placebo (4274 men), nor was the incidence higher in the 2199 men taking part in open-label extensions. Blood pressure and heart rate were unaffected.

The overall incidence of abnormal vision was 6.5% for Viagra ® versus 0.4% for placebo. Abnormal vision was commonly described as a transient color tinge to vision, an increased perception of light, or blurred vision. Most cases were mild or moderate. Patients with untreated proliferative diabetic retinopathy or macular degeneration have not been included in significant numbers. Two patients with retinal detachment have been reported.

It is a truism of drug regulation that, at the time of introduction, we expect to have a pretty clear idea of efficacy, but that the full safety profile of a medication is only learnt when many patients have used it over a reasonable period of time. The evidence thus far is that Viagra® is effective and safe. Most of the men studied had medical conditions associated with impotence, although men with spinal injuries were excluded. While more experience is required, the picture that is emerging is an optimistic one that this medication will bring relief to a substantial proportion of men suffering from a condition that has hitherto eluded safe, effective and acceptable treatment.

Treatment efficacy for Viagra ® is about the same as for intracavernosal injection or intraurethral application of alprostadil (see below). Adverse effects are, however, different. Because of the mode of action of Viagra ®, potentiation of the blood pressure-lowering effects of nitrates is expected, and indeed was demonstrated in early studies. Its use in men treated with organic nitrates is therefore contraindicated.

Viagra is a registered trademark of Pfizer Corp.