Sildenafil 2.pdf

For the treatment of male erectile Licensed Indication
Sildenafil, an oral phosphodiesterase 5 inhibitor is ‘The treatment of erectile dysfunction, which is the licensed for the treatment of erectile dysfunction in the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance. In order for Viagra to be effective sexual stimulation is Dosage and Administration
The recommended dose is 25-100mg taken orally Viagra is not indicated for use by women' 1 when required approximately 1 hour before sexualactivity. The maximum recommended dosing Patients who are taking organic nitrates (or othernitric oxide donors such as amyl nitrite) in any Clinical Efficacy
form, regardless of the frequency, due to a Sildenafil (primarily at doses of 25-100mg) has been potentiation of hypotensive effects.
evaluated in approximately 4,000 men with erectile Men for whom sexual activity is inadvisable.
dysfunction of broad-spectrum aetiology in 21 randomised, double-blind, placebo-controlled, trials of hypotension (BP < 90/50mmHg), recent history of up to 6 months duration. Of these 21 studies only 4 stroke or myocardial infarction (MI) and known have been published in full;5,6,7 11 are available as hereditary degenerative retinal disorders such as abstract & posters supported by data in the New Drug Application (NDA)8 filed with the FDA. Six are only Patients with a known hypersensitivity to any available in the FDA-NDA. Data on the remaining Background information
The initial phase II studies measured duration of Male erectile dysfunction (ED), which is defined as the penile rigidity, using a Rigiscan, following visual ‘inability to achieve or maintain an erection sufficient sexual stimulation. Generally an increased duration of for sexual intercourse’, affects approximately 1 in 10 rigidity > 60% was seen with increasing doses of sildenafil. The clinical significance of these results isdifficult to quantify.8 The causes of erectile dysfunction are many including;neurogenic or Sixteen trials evaluated the effect of treatment with psychogenic (anxiety), hormonal (hypogonadism), sildenafil (10-200mg) for 4 - 26 weeks on erectile drug induced (responsible for up to 25% cases), or function and sexual function in men (>18 years old) anatomical (peyronies disease) factors. Additionally, certain diseases predispose patients to erectile dysfunction, for example up to 50% of men with Nine trials evaluated fixed doses of sildenafil and 7 diabetes, 40% of men with heart disease and 90% of allowed dose titration according to response and men with severe depression, suffer with ED.2,3 tolerability. In the 8 dose titration studies there was a strong tendency to migrate to the highest dose Guidelines for the diagnosis and treatment of ED have available (>50% migrated to 100mg). More than 80% emphasised the need for a thorough assessment of of patients completed these studies, data on patient the problem; a detailed medical and psycho-social withdrawals were not consistently reported. Generally, history, clinical examination to elucidate a cause (ED both treatment-related adverse events and insufficient can be an early sign of a systemic condition), response were responsible for <5% of withdrawals.
education of the patient and partner, and inclusion ofthe patient’s needs and preferences in the decision- In each of the studies significant (p<0.0001) improvements were apparent with sildenafil treatment compared to placebo in relation to frequency of The treatment options available to manage ED penetration and maintenance of erection after include psychosexual counselling, hormonal therapy penetration. Sildenafil treatment, was also associated (for those with hypogonadism), prosthetic penile with improved erections (72% vs 18%), an increase in implants, vacuum devices, vascular surgery, and successful attempts at intercourse and, where intracavernosal injection or transurethral therapy with 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 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 Reduced responses were seen in diabetic men with ED with ED in 21 randomised double-blind, placebo-controlled and men with ED post radical prostatectomy. Improved trials over periods of up to 6 months. Sildenafil 25 - 100mg erections were only reported in 50-60% and 40-50% of was effective in approximately 75% of patients, although lower responses were apparent in diabetic men and those with ED following a radical prostatectomy.
Patients enrolled in these randomised, double-blind,placebo-controlled trials were entered into open label Adverse events seen in clinical trials were generally extension studies. The outcome of these studies is not yet transient and predictable. Visual abnormalities were noted particularly at doses above 100mg. There are concerns Adverse Effects
regarding the possible long-term consequences of this Adverse events seen in clinical trials were predominantly adverse effect. A temporal association with serious transient, mild or moderate in nature and dose related. Only adverse events, including MI, has been reported. Sildenafil 2.5% of patients withdrew from sildenafil treatment due to should not be co-administered with nitrates since large and an adverse event compared to 2.3% on placebo. The majority of adverse events seen with sildenafil related to itsknown pharmacological properties; vasodilatation Careful targeting of the drug to those who require treatment (including headache, flushing, nasal congestion), will be essential since it is anticipated that there will be a gastrointestinal events (dyspepsia) and visual effects 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 The adverse effects on vision, reported as light sensitivity against the prescribing of sildenafil (except in exceptional and bluish vision lasting from a few minutes to a few hours, have been recorded particularly at high doses. No effects References
on other objective measures of visual function, e.g. visual 1. Anon. Viagra. Summary of Product Characteristics.
acuity, have been reported. Any long-term consequences of 2. Wagner G, de Tejada IS. Update on male erectile dysfunction. BMJ 1998; 316: 678-682.
No clinically significant changes in blood pressure, heart 3. Holmes S, Kirby R & Carson C. Fast Facts – Male rate or ECG and no increase in the development of serious Erectile Dysfunction. Health Press. Oxford 1997.
cardiovascular events were seen with sildenafil in clinical 4. Von Heyden B, Intracavernous Pharmacotherapy for trials. Sildenafil has not been shown to have a direct effect Impotence: Selection of Appropriate Agent and Dose.
on platelet aggregation or an effect on sperm motility or morphology. Priapism has been reported in post marketing 5. Boolell M et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction. Br.J.Urol. 1996; 37: 257- During post-marketing surveillance, serious adverse events including MI, angina, sudden cardiac death and ventricular 6. Goldstein I et al for the Sildenafil Study Group. Oral arrhythmia have been reported in temporal association with sildenafil in the treatment of erectile dysfunction.
N.Engl.J.Med 1998; 338: 1397-1404.
7. Rendell MS, Rajfer J, Wicker PA et al. Sildenafil for Treatment of Erectile Dysfunction in Men With Sildenafil is avaliable in three tablet strenghts; 25mg, 50mg Diabetes. A Randomized Controlled Trial. JAMA & 100mg. These are provided in packs of 4 and 8 tablets.
The current basic price per tablet is £4.15 for 25mg, £4.84 8. FDA Centre for Drug Evaluation and Research. Joint for 50mg and £5.88 for a 100mg tablet.
clinical review for NDA-20-895. January 1998.
9. Morales A et al. Clinical safety of oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction.
ED is currently an under reported condition. The launch of Int.J.Impot.Res. 1998; 10: 69-74.
sildenafil is anticipated to increase the number of patientspresenting with ED. For each patient a careful evaluation Date: July 2000
THIS SUMMARY SHEET REPLACES SS99/15 WHICH SHOULD BE REMOVED AND DESTROYED
MTRAC, Department of Medicines Management, Keele University

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