Erectile dysfunction

Drug Store News, Feb 15, 1999 by Carol Dickson McKee

Amyl nitrate inhalant and related illicit recreational drugs, "poppers" (so called because the glass ampules must be popped open), are used by some to enhance sex. Since fatal interactions with sildenaffi have been reported, caution is in [order.sup.17].

Drugs which affect sildenafil's [metabolism.sup.12-20]

Sildenafil is broken down in the liver, and its metabolism is primarily mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Concomitant use of agents that inhibit these isoenzymes may, therefore, decrease sildenafil clearance and increase sildenafil serum concentrations and adverse effects. Conversely, concomitant use of CYP3A4 inducers would be expected to speed up the metabolism of sildenafil, resulting in lower sildenafil serum concentrations and possibly resulting in subtherapeutic erectile effects. [(Table 3).sup.(19)(20)]

Which patients should not take [sildenafil.sup.12-18]?

Sildenafil is absolutely contraindicated in patients taking any type of nitrates. The degree of cardiovascular risk associated with sexual activity should be considered for each patient, based upon his cardiovascular status, prior to initiating any treatment for erectile dysfunction. The American College of Cardiology, in conjunction with the American Heart Association, is developing an expert consensus document titled, "The Use of Sildenafil in Patients at Clinical Risk from Cardiovascular Effects." This was expected to be released in December 1998. (More information may be obtained by calling the AHA News Media Relations at 214-706-1135 or 214-706-1279.) Interim recommendations include:

Sildenafil is absolutely contraindicated in patients taking any type of nitrates, including "poppers."

Caution is advised when considering the use of sildenafil in patients with active coronary ischemia who are not on nitrates; patients with congestive heart failure and borderline low blood pressure and volume status; patients on complicated multi-drug antihypertensive programs and patients having conditions or taking medications which may cause increased serum sildenafil concentrations or prolong sildenafil's half-life.

The ACC and AHA also currently recommend allowing at least 24 hours to elapse before using nitrates in patients who have taken sildenafil. If a patient on sildenafil is inadvertently given a nitrate and develops severe hypotension, the ACC and AHA currently recommend they be treated with aggressive fluids and agents, such as phenylephrine or norepinephrine, to increase blood [pressure.sup.18].

As with any medication, sildenafil is contraindicated in patients with hypersensitivity to any component of the tablet. Sildenafil is not indicated for use in women.

Dosage decreases may be necessary in patient populations likely to have reduced sildenafil clearance and increased sildenafil serum concentrations. These include "seasoned citizens" over the age of 65 years, patients with decreased renal or hepatic function and those concomitantly taking medications which inhibit the hepatic metabolic CYP3A4 system. Dosage increases may be necessary in patients concomitantly taking medications that induce the hepatic metabolic CYP3A4 system.