Description
Combining sildenafil with nitrates causes profound, potentially fatal hypotension; this combination is absolutely contraindicated.
Mechanism
Nitrates increase cyclic GMP via guanylate cyclase stimulation, causing vascular smooth muscle relaxation; sildenafil inhibits PDE5, preventing cGMP degradation. The combined effect causes an uncontrolled and potentially catastrophic reduction in blood pressure.
Clinical Significance
Mean blood pressure drops of >25 mmHg have been documented; cardiovascular collapse, syncope, MI, and death have been reported with concurrent use.
Management
Absolute contraindication. Patients who use sildenafil for erectile dysfunction must be counseled to avoid ALL nitrate forms (sublingual, oral, transdermal, IV). If nitrate use is necessary after sildenafil, wait at least 24 hours (48 hours for tadalafil).