Sildenafil Glyceryl trinitrate

Patients suffering from angina pectoris should also use glyceryl trinitrate or isosorbide dinitrate as usual for pre-exertional prophylaxis 10 min before intercourse. They should be aware of the potentially fatal interaction of sildenafil (Viagra) with nitrates (see above, p. 545). 

The pressure-lowering effect of a step-wise intravenous infusion of glyceryl trinitrate was significantly increased in 12 healthy volunteers treated for 4 days with sildenafil (Viagra) 25 mg tds episodes of symptomatic hjrpotension were also more frequent with sildenafil (113). When sublingual glyceryl trinitrate was used, the reduction in systolic blood pressure was four-fold greater in association with sildenafil. 

An elderly man with anginal pain died after treatment with glyceryl trinitrate (114). The family physician discovered that the man had also taken sildenafil, and he suggested suicidal intent, since he claimed that the patient was aware of the adverse cardiac events of the association of these two drugs. 

Hypertensive patients taking amlodipine, in contrast to glyceryl trinitrate, had only a minor supplementary fall in blood pressure when challenged with a single dose of sildenafil, and a few had a mild to moderate headache (46). 

Diltiazem is metabolized by CYP3A4 and was held responsible for unanticipated prolonged hypotension after sublingual glyceryl trinitrate in a patient who underwent coronary angiography 2 days after last using sildenafil (47). 

Potentiation by sildenafil of the hypotensive effects of glyceryl trinitrate and amlodipine has been investigated. The fall in systolic blood pressure with glyceryl trinitrate was amplified four-fold by sildenafil in healthy subjects. 

The phosphodiesterase type-5 inhibitors potentiate the hypotensive effects of nitrates in a proportion of patients, which might re-suit in potentiaiiy serious hypotension or even precipitate myocardiai infarction. Therefore, the concurrent use of sildenafil, tadalafil or vardenafil with organic nitrates (glyceryl trinitrate (nitroglycerin), isosorbide dinitrate, isosorbide mononitrate, etc.) is contraindicated. The concurrent use of nicorandil and all phosphodiesterase type-5 inhibitors is also contraindicated. 

A postmarketing report from the FDA in the US for the period late March to July 1998 briefly lists 69 fatalities after taking sildenafil. These were mostly in middle-aged and elderly men (average age 64), 12 of whom had also taken glyceryl trinitrate (nitroglycerin) or a nitrate medication, but it is not clear what part (if any) the nitrates played in the deaths. ... 

In a limited and preliminary study it was reported that no blood pressure alteration was seen when a small dose of glyceryl trinitrate (amount not specified) was given as a dermal patch while subjects were taking 50 mg of sildenafil. In addition, the beneficial effects of the glyceryl trinitrate on the radial artery pressure waveform were approximately doubled, and persisted for up to 8 hours. ... 

---