Published: May 2001

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Viagra Reminder: Ask! Don't be Shy!

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Prescriber Update 21: 8-9
May 2001

Medsafe Editorial Team

Sildenafil (Viagra™) plus nitrates may result in a precipitous fall in blood pressure. Do not use nitrates to relieve an angina attack if the patient has recently taken sildenafil - use other angina treatments instead. Doctors and nurses must ask about Viagra use before administering glyceryl trinitrate (GTN) spray or any other nitrate preparation.

Sildenafil should not be prescribed if there is regular or intermittent nitrate use

Sildenafil is contraindicated in patients taking nitrates for cardiovascular disease. This includes all dose forms such as oral (e.g. GTN spray, sublingual tablets, slow release preparations), injectable (e.g. sodium nitroprusside) and topical (e.g. transdermal patches) nitrates. Remember to ask patients about nitrates used recreationally, e.g. amyl nitrate. Also remind patients who are using nitrates, that they must not take sildenafil.

Sildenafil, through inhibition of phosphodiesterase type 5, enhances the effect of local nitric oxide release in the corpus cavernosum during sexual stimulation. This results in arterial and venous dilation and inflow of blood. If exogenous nitrates are given, there will be a systemic rise in nitric oxide concentrations, which in combination with sildenafil, potentiates the vasodilatory effect of nitrates. This can cause a significant drop in blood pressure (BP) and may be life threatening.

Doctors, nurses and paramedics must ask patients (men and women²) about recent Viagra™ use before administering GTN spray or any other nitrate.

If the patient has taken sildenafil, give analgesia - NOT nitrates - to relieve angina pain

When a patient who has taken sildenafil develops acute angina, other anti-angina treatments must be used instead of nitrates, for example: aspirin, morphine, oxygen, β-adrenergic blockers (note: the potentiating effect on BP reduction is not observed with sildenafil when used in combination with non-nitrate vasodilators), and heparin. In serious or complicated cases of angina or chest pain, advice should be sought from a cardiologist, and transfer of the patient to hospital in an ambulance is recommended.

It is unknown when nitrates can be safely administered to patients who have taken sildenafil.¹ The risk of an exaggerated BP response with nitrates decreases with time from the dose of sildenafil. Based on pharmacokinetics, plasma levels of sildenafil are low at 24 hours¹ and some authors suggest that after 24 hours the administration of a nitrate may be considered². However some conditions such as age over 65 years, hepatic impairment, severe renal impairment or use of cytochrome P450 3A4 inhibitors (including erythromycin, ketoconazole, diltiazem and HIV protease inhibitors) can result in reduced clearance of sildenafil. In such patients, the time frame for withholding nitrates will be longer.¹ The advice of a cardiologist or emergency physician should be sought in situations of doubt. If the decision is made to administer nitrates, close monitoring must be provided with proper facilities available for fluid and vasopressor support², and emergency resuscitation.

Inadvertent co-administration of nitrates and sildenafil can cause severe hypotension

In the event of inadvertent co-administration of nitrates and sildenafil, close monitoring must be undertaken in an environment where fluid replacement, vasopressor support and emergency resuscitation can be provided (usually in hospital). With significant hypotension, place the patient in the Trendelenburg position, administer intravenous fluid and consider using alpha-agonists in severe cases (bearing in mind that these may exacerbate any coronary ischaemia present).

Please refer to the full data sheet¹ (available on the Medsafe website: www.medsafe.govt.nz) before prescribing Viagra™.

^a Sildenafil is approved only for use in men, but unapproved use by women may occur.

References

1. Pfizer Pty Ltd. Viagra data sheet. February 2001. www.medsafe.govt.nz/Profs/Datasheet/v/viagratab.pdf
2. Cheitlin MD, Hutter AM, Brindis RG et al. ACC/AHA Expert Consensus Document. Use of sildenafil (Viagra) in patients with cardiovascular disease. 1999. http://circ.ahajournals.org/cgi/content/full/99/1/168