(August 2006).
|
This
drug has been "archived" and will not be actively updated except
for a compelling reason or request (August 2006). |
SILDENAFIL
SUMMARY SHEET
PDF VERSION OF SUMMARY SHEET AVAILABLE
| TRADE NAME: Viagra® |
For the treatment of male erectile dysfunction
Licensed Indication
‘The treatment of erectile dysfunction, which is the inability to achieve or
maintain a penile erection sufficient for satisfactory sexual performance. In
order for Viagra to be effective sexual stimulation is required.
Viagra is not indicated for use by women'1
Sildenafil is contra-indicated in:
Background information
Male erectile dysfunction (ED), which is defined as the ‘inability to achieve
or maintain an erection sufficient for sexual intercourse’, affects
approximately 1 in 10 men. Incidence increases with age.
The causes of erectile dysfunction are many including; neurogenic or vasculogenic abnormalities, psychogenic (anxiety), hormonal (hypogonadism), drug induced (responsible for up to 25% cases), or anatomical (peyronies disease) factors. Additionally, certain diseases predispose patients to erectile dysfunction, for example up to 50% of men with diabetes, 40% of men with heart disease and 90% of men with severe depression, suffer with ED.2,3
Guidelines for the diagnosis and treatment of ED have emphasised the need for a thorough assessment of the problem; a detailed medical and psycho-social history, clinical examination to elucidate a cause (ED can be an early sign of a systemic condition), education of the patient and partner, and inclusion of the patient’s needs and preferences in the decision-making process.2,3
The treatment options available to manage ED include psychosexual counselling, hormonal therapy (for those with hypogonadism), prosthetic penile implants, vacuum devices, vascular surgery, and intracavernosal injection or transurethral therapy with vasodilators.2,3,4
Sildenafil, an oral phosphodiesterase 5 inhibitor is licensed for the treatment of erectile dysfunction in the UK.
Dosage and Administration
The recommended dose is 25-100mg taken orally when required approximately 1 hour
before sexual activity. The maximum recommended dosing frequency is once per
day.1
Clinical Efficacy
Sildenafil (primarily at doses of 25-100mg) has been evaluated in approximately
4,000 men with erectile dysfunction of broad-spectrum aetiology in 21 randomised,
double-blind, placebo-controlled, trials of up to 6 months duration. Of
these 21 studies only 4 have been published in full;5,6,7 11 are
available as abstract & posters supported by data in the New Drug
Application (NDA)8 filed with the FDA. Six are only available in the
FDA-NDA. Data on the remaining study are not available.
The initial phase II studies measured duration of penile rigidity, using a Rigiscan, following visual sexual stimulation. Generally an increased duration of rigidity > 60% was seen with increasing doses of sildenafil. The clinical significance of these results is difficult to quantify.8
Sixteen trials evaluated the effect of treatment with sildenafil (10-200mg) for 4 - 26 weeks on erectile function and sexual function in men (>18 years old) with ED (>6 months duration).
Nine trials evaluated fixed doses of sildenafil and 7 allowed dose titration according to response and tolerability. In the 8 dose titration studies there was a strong tendency to migrate to the highest dose available (>50% migrated to 100mg). More than 80% of patients completed these studies, data on patient withdrawals were not consistently reported. Generally, both treatment-related adverse events and insufficient response were responsible for <5% of withdrawals.
In each of the studies significant (p<0.0001) improvements were apparent with sildenafil treatment compared to placebo in relation to frequency of penetration and maintenance of erection after penetration. Sildenafil treatment, was also associated with improved erections (72% vs 18%), an increase in successful attempts at intercourse and, where measured, an improvement in the number of erections hard enough for intercourse (statistical significance was inconsistently reported for these variables).
In all cases increasing improvement was apparent over the dosage range 25-100mg.5-8
Reduced responses were seen in diabetic men with ED and men with ED post radical prostatectomy. Improved erections were only reported in 50-60% and 40-50% of these patients respectively.7,8
Patients enrolled in these randomised, double-blind, placebo-controlled trials were entered into open label extension studies. The outcome of these studies is not yet available.7
Adverse Effects
Adverse events seen in clinical trials were predominantly transient, mild or
moderate in nature and dose related. Only 2.5% of patients withdrew from
sildenafil treatment due to an adverse event compared to 2.3% on placebo. The
majority of adverse events seen with sildenafil related to its known
pharmacological properties; vasodilatation (including headache, flushing, nasal
congestion), gastrointestinal events (dyspepsia) and visual effects (abnormal
vision).1,5-8
The adverse effects on vision, reported as light sensitivity and bluish vision lasting from a few minutes to a few hours, have been recorded particularly at high doses. No effects on other objective measures of visual function, e.g. visual acuity, have been reported. Any long-term consequences of this side effect are not known.1,8,9
No clinically significant changes in blood pressure, heart rate or ECG and no increase in the development of serious cardiovascular events were seen with sildenafil in clinical trials. Sildenafil has not been shown to have a direct effect on platelet aggregation or an effect on sperm motility or morphology. Priapism has been reported in post marketing surveillance studies.1,8,9
During post-marketing surveillance, serious adverse events including MI, angina, sudden cardiac death and ventricular arrhythmia have been reported in temporal association with sildenafil.1
Costs
Sildenafil is avaliable in three tablet strenghts; 25mg, 50mg & 100mg. These
are provided in packs of 4 and 8 tablets. The current basic price per tablet is
£4.15 for 25mg, £4.84 for 50mg and £5.88 for a 100mg tablet.
Summary
ED is currently an under reported
condition. The launch of sildenafil is anticipated to increase the number of
patients presenting with ED. For each patient a careful evaluation of the
potential underlying cause of the condition should be undertaken, before
sildenafil treatment is considered.
Sildenafil has been evaluated in approximately 4,000 men with ED in 21 randomised double-blind, placebo-controlled trials over periods of up to 6 months. Sildenafil 25 - 100mg was effective in approximately 75% of patients, although lower responses were apparent in diabetic men and those with ED following a radical prostatectomy.
Adverse events seen in clinical trials were generally transient and predictable. Visual abnormalities were noted particularly at doses above 100mg. There are concerns regarding the possible long-term consequences of this adverse effect. A temporal association with serious adverse events, including MI, has been reported. Sildenafil should not be co-administered with nitrates since large and sudden drops in BP have occurred.
Careful targeting of the drug to those who require treatment will be essential since it is anticipated that there will be a broad market for the drug in men with perceived reduced sexual functioning in the hope of improving performance. The Department of Health has issued guidance advising against the prescribing of sildenafil (except in exceptional circumstances) at NHS expense.
References
THIS SUMMARY SHEET REPLACES SS99/15 WHICH SHOULD BE REMOVED AND DESTROYED
| Date: July 2000 | SS00/18 |
© MTRAC, Department of Medicines Management