Time-dependent interactions of the hypotensive effects of sildenafil citrate and sublingual glyceryl trinitrate

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT center dot Co-administration of inhibitors of phosphodiesterase type 5 with organic nitrates can cause profound hypotension. center dot For this reason, it is recommended that sildenafil and organic nitrates are not administered within 24 h of one another. center dot However, the time course of the interaction between sildenafil and sublingual glyceryl trinitrate (GTN) has not previously been investigated. WHAT THIS STUDY ADDS center dot In men with angina there is an interaction between oral sildenafil and sublingual GTN for >= 8 h, but from 6 h this interaction is not more than additive. center dot These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h. To investigate the time course of the hypotensive interaction between sildenafil and glyceryl trinitrate (GTN). Two double-blind, placebo-controlled, randomized, crossover studies were performed. Subjects were challenged with sublingual GTN 400 mu g at different times after oral sildenafil 100 mg. After each GTN challenge frequent measures of blood pressure (BP) were made. In the first study GTN was given 1-48 h after sildenafil/placebo to 33 healthy men. In the second study GTN was given 1-8 h after sildenafil/placebo to 20 men with stable angina. In healthy men there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN only at 1 h. In angina patients, there was a greater mean maximum reduction in BP with sildenafil/GTN than with placebo/GTN for up to 8 h. The mean (95% confidence interval) differences in maximum systolic BP reduction (mmHg) at 1, 4, 6 and 8 h were -16 (-12, -21), -12 (-4, -20), -6 (1, -12) and -9 (-3, -15), all P < 0.05 except at 6 h (NS). At 6 and 8 h the interaction was not more than additive, and hypotensive symptoms did not occur. In men with angina there is an interaction on BP reduction between sildenafil and GTN for >= 8 h after sildenafil administration, but this is no more than additive from 6 h. These data may be helpful to clinicians who are considering the use of GTN in patients presenting with angina who have received sildenafil within 24 h.