Which medications interact with nitroglycerin?

Medications That Interact with Nitroglycerin

Phosphodiesterase-5 (PDE-5) inhibitors are absolutely contraindicated with nitroglycerin and must not be administered within 24 hours of sildenafil or vardenafil, or within 48 hours of tadalafil, due to risk of life-threatening hypotension. 1, 2

Absolute Contraindications

PDE-5 Inhibitors (Most Critical Interaction)

• Sildenafil (Viagra): Withhold nitroglycerin for at least 24 hours after last dose 1, 2
• Vardenafil (Levitra): Withhold nitroglycerin for at least 24 hours after last dose 1, 2
• Tadalafil (Cialis): Withhold nitroglycerin for at least 48 hours after last dose due to longer half-life (17.5 hours) 1, 3
• The combination can cause profound hypotension, large and protracted decreases in systemic blood pressure, decreased coronary blood flow in stenotic vessels, and even death 2, 3, 4
• The hemodynamic interaction between tadalafil and nitroglycerin lasts 24 hours but resolves by 48 hours 3

Soluble Guanylate Cyclase Stimulators

• Concomitant use is absolutely contraindicated 2
• These drugs potentiate the vasodilatory effects through the same nitric oxide pathway

Significant Drug Interactions Requiring Monitoring

Heparin

• Intravenous nitroglycerin reduces the anticoagulant effect of heparin 2
• Activated partial thromboplastin times (APTT) must be monitored in patients receiving both medications 2
• It is unknown if this effect occurs with sublingual nitroglycerin 2

Alteplase (tPA)

• Intravenous nitroglycerin decreases the thrombolytic effect of alteplase 2
• Exercise caution in patients receiving sublingual nitroglycerin during alteplase therapy 2

Ergotamine and Related Drugs

• Oral nitroglycerin markedly decreases first-pass metabolism of dihydroergotamine, increasing its bioavailability 2
• Ergotamine is known to precipitate angina pectoris 2
• Patients receiving sublingual nitroglycerin should avoid ergotamine and related drugs, or be monitored for symptoms of ergotism 2

Aspirin

• The vasodilatory and hemodynamic effects of nitroglycerin may be enhanced by concomitant aspirin administration 2
• This is generally a beneficial interaction in acute coronary syndromes, but requires awareness of potentially greater blood pressure reduction 2

Interactions Affecting Nitroglycerin Efficacy

Tricyclic Antidepressants and Anticholinergic Drugs

• Amitriptyline, desipramine, doxepin, and other tricyclics cause dry mouth and diminished salivary secretions 2
• This may impair dissolution of sublingual nitroglycerin tablets 2
• Consider increasing salivation with chewing gum or artificial saliva products to aid dissolution 2

Alcohol

• Concomitant use of nitrates and alcohol may cause hypotension 2
• This interaction can be clinically significant and patients should be counseled accordingly 2

Clinical Context and Monitoring

Hypotension Risk

• Nitroglycerin is contraindicated when systolic BP <90 mmHg or ≥30 mmHg below baseline 5, 2
• Rare instances of severe nitrate-induced hypotension accompanied by marked bradycardia and syncope have been reported 2, 6
• Seven episodes of simultaneous severe hypotension and bradycardia were observed in patients with acute MI receiving nitroglycerin, with no initial tachycardia preceding the bradycardia 6

Common Pitfalls

• Nearly 10% of patients cannot tolerate nitrates due to disabling headaches or dizziness 7
• Headache is reported by up to 82% of patients in placebo-controlled trials 7
• Nitrate-induced hypotension is common but often asymptomatic 7
• Use of nitrates in patients who experience syncope after nitroglycerin administration is contraindicated 7

Laboratory Test Interference

• Nitrates may interfere with the Zlatkis-Zak color reaction, causing falsely decreased serum cholesterol readings 2