Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina

J Am Coll Cardiol. 2000 Jul;36(1):25-31. doi: 10.1016/s0735-1097(00)00705-1.


Objective: We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina.

Background: Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs.

Methods: Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 microg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug.

Results: The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, -52/-29 mm Hg) were greater than the effects of placebo plus ISMN on BP (-25/-15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (-36/-21 mm Hg) compared with placebo plus GTN (-26/-12 mm Hg; p < 0.01).

Conclusions: Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism
  • Administration, Oral
  • Aged
  • Angina Pectoris / drug therapy*
  • Angina Pectoris / enzymology
  • Angina Pectoris / physiopathology
  • Blood Pressure / drug effects*
  • Contraindications
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Drug Interactions
  • Drug Synergism
  • Drug Therapy, Combination
  • Humans
  • Isosorbide Dinitrate / analogs & derivatives
  • Isosorbide Dinitrate / therapeutic use
  • Male
  • Middle Aged
  • Nitric Oxide Donors / therapeutic use*
  • Nitroglycerin / therapeutic use
  • Phosphodiesterase Inhibitors / pharmacology*
  • Piperazines / pharmacology*
  • Purines
  • Sildenafil Citrate
  • Sulfones


  • Delayed-Action Preparations
  • Nitric Oxide Donors
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Sulfones
  • Sildenafil Citrate
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Nitroglycerin
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate