Tadalafil and Nitrate Contraindications

Introduction to Contraindications

The American College of Cardiology states that the concurrent use of tadalafil with isosorbide mononitrate is absolutely contraindicated due to the risk of life-threatening hypotension 1

Both tadalafil and isosorbide mononitrate work through the nitric oxide pathway, causing profound and potentially fatal blood pressure drops when combined, as noted by the American College of Cardiology 2, 3, 4
Tadalafil inhibits phosphodiesterase-5, which degrades cyclic guanosine monophosphate (cGMP), while nitrates like isosorbide mononitrate increase cGMP production through nitric oxide release, according to the American College of Cardiology 2, 3
This dual mechanism creates markedly exaggerated and prolonged vasodilation that can result in profound hypotension, myocardial infarction, stroke, or death, as reported by the American College of Cardiology 2, 3, 4

Patients must wait at least 48 hours after the last dose of tadalafil before any nitrate can be safely administered, as recommended by the American Academy of Family Physicians and the American College of Cardiology 5, 6, 1
Tadalafil has a half-life of 17.5 hours, meaning the active ingredient remains in the body for more than 2 days, according to the American College of Cardiology 6, 1

Patients taking long-acting nitrate therapy such as isosorbide mononitrate should not use tadalafil, as stated by the American College of Cardiology 6, 1
If a patient desires to use a phosphodiesterase-5 inhibitor, the decision must be guided by whether continued nitrate therapy is medically necessary versus available alternative treatments for their cardiac condition, according to the American College of Cardiology 6, 1

Patients with chronic coronary disease requiring long-acting nitrate therapy must use non-pharmacologic approaches or alternative treatments for erectile dysfunction that do not interact with nitrates, as recommended by the American College of Cardiology 6, 1
Consider transitioning from nitrate therapy to alternative antianginal agents such as beta-blockers, calcium channel blockers, or ranolazine if clinically appropriate, as suggested by the American College of Cardiology 6, 1