Viagra

Sildenafil (Viagra®)

Pharmacology: Sildenafil facilitates erections associated with sexual stimulation. It will not act if the man is not sufficiently mentally aroused or his peripheral autonomic nerves are absent (e.g. radical prostatectomy). It acts by inhibiting phosphodiesterase isoenzyme 5 (PDE5), thus prolonging cyclic guanosine monophosphate (cGMP) activity in erectile tissue, and enhancing the vasodilating actions of nitric oxide, which is released in response to sexual stimulation.⁵ Sildenafil is rapidly absorbed from the gut peaking 30-120 min. after an oral dose. At peak effect it lowers mean systolic supine blood pressure (8 mmHg) in healthy volunteers. The drug is eliminated by liver metabolism (CYP3A4) with a half-life of 3-5 hours. Half-life is prolonged in patients > 65 years and in patients with renal or hepatic impairment.

Effectiveness: Six randomized, double-blind, clinical trials comparing sildenafil versus placebo were published prior to June, 1999.^6-10 Each trial enrolled between 12 and 532 patients over a duration of 2 to 24 weeks. In the best designed trial of 329 patients over 12 weeks, intercourse was reported successful in 59% of patients taking sildenafil as compared to 15% of patients taking placebo (absolute benefit increase 44%, NNT = 2 to achieve one success).⁶

Adverse effects: The most common adverse effects, as absolute risk increase over placebo, were headache 14%, flushing 17%, dyspepsia 4%, rhinitis 4% and visual disturbance 1%.⁷ None of the studies assessed the effects of long-term sildenafil use. Such studies are needed, particularly in patients with a history of retinal and cardiovascular disorders.

Serious rare side effects include priapism, severe hypotension, heart attack, stroke and death.

Contraindications: Patients taking or at risk of requiring nitrates in any form. Patients in whom sexual activity is inadvisable because of their cardiovascular status (e.g. MI or CVA within 6 months, heart failure, unstable angina, hypotension, uncontrolled hypertension, aortic stenosis, etc.). Patients with retinitis pigmentosa, anatomical deformities of the penis, conditions predisposing to priapism (e.g. sickle cell anemia, multiple myeloma), or receiving multiple antihypertensive drugs.

Precautions: There is no safety information on patients excluded from the trials (e.g. patients with alcoholism, active peptic ulcer, proliferative diabetic retinopathy, etc.). Inhibitors of CYP3A4 such as erythromycin, ketoconazole, grapefruit juice and others would be expected to increase the magnitude and duration of response to sildenafil.

Dosage and cost: The drug should be taken on an empty stomach 1 hour before intended sexual activity and no more than once daily. Dose range 25-100 mg. As with most drugs start with the lowest dose, 25 mg, and increase only if necessary. Since the cost of each tablet is similar ($10 - $12), prescribing the higher dose tablets and dividing them can substantially reduce the cost.