Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
25 mg, 50 mg and 100 mg tablets
Indication: erectile dysfunction
AMH Section 13.3
A normal erection results from vasodilatation in the penis. The mechanism involves the release of nitric oxide in the corpus cavernosum. This activates the enzyme which produces cyclic guanosine monophosphate (cGMP). By inhibiting the degradation of cGMP, sildenafil maintains the relaxation of smooth muscle in the corpus cavernosum. The drug has no direct action, but enhances the effect of nitric oxide. As the release of nitric oxide depends on sexual arousal, sildenafil will only be effective when there is sexual stimulation.
The peak plasma concentration is reached within two hours of a dose. An oral dose of 50 mg one hour before intercourse is recommended. The dose may be adjusted up or down depending on response, but should not exceed 100 mg. Sildenafil has a half-life of 3-5 hours. It is metabolised to an active metabolite which is mainly excreted in the faeces. The metabolism involves cytochrome P450 3A4 so clearance is reduced by cimetidine, erythromycin and ketoconazole.
Two trials in the U.S.A. studied 861 men with erectile dysfunction. Sildenafil was more effective than placebo for men with organic or psychogenic causes of their impotence.1 One of these studies was a 12-week dose escalation study. In the last month of the study, 69% of the attempts at sexual intercourse were successful in men taking sildenafil compared to 22% of men in the placebo group. In the 21 randomised trials of sildenafil, it has improved erectile function in 59% of patients with diabetes, 83% of patients with spinal cord injury and 43% of patients with a history of radical prostatectomy.
The drug was launched in the U.S.A. in March 1998. By July, 3.6 million prescriptions had been dispensed, but 123 deaths had been reported. Many of these deaths were due to cardiovascular events. Sildenafil reduces the blood pressure and this may be severe if the patient is also taking nitrates. Before sildenafil is prescribed, the patient's cardiovascular status should be assessed. The drug is contraindicated if the patient is using nitrates.
Adverse effects which occur more frequently in patients taking sildenafil, compared to placebo, are headache, flushing and dyspepsia. Some patients report changes in vision; a colour tinge is most commonly reported.
Until the approval of sildenafil, the most effective treatment for impotence was injectable prostaglandin E1.2 As sildenafil is easier to administer, and appears not to cause priapism, more impotent men are likely to seek treatment. While sildenafil does not work in every case and has mainly been assessed subjectively, it seems likely to become the treatment of choice. Prescribers should still continue to assess patients with erectile dysfunction so that other disorders are not overlooked. Similarly, the patient's problem may be due to other drugs they are taking.
Sildenafil is expensive and, if approved for subsidy, will put a strain on the drug budget. Insurers will have to decide the frequency of sexual activity they will fund. How much is enough?
- Sildenafil Study Group. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998;338:1397-404.
- Handelsman DJ, Conway AJ. The management of erectile dysfunction. Aust Prescr 1998;21:46-8.