Isosorbide dinitrate × Vardenafil

Vardenafil and isosorbide dinitrate drive the same NO–cGMP signalling pathway from opposite ends. The dinitrate releases nitric oxide in the body and boosts cGMP synthesis in vascular smooth muscle; vardenafil blocks phosphodiesterase-5 and slows the breakdown of that same cGMP. Cyclic GMP accumulates from both directions at once, vascular tone collapses, and additive vasodilation progresses up to refractory hypotension that responds poorly to fluids and vasopressors while both drugs remain active. Unlike sublingual nitroglycerin with its minutes of action, isosorbide dinitrate works for hours and its extended-release forms for most of the day, so the window of danger is stretched out. The Levitra SmPC lists nitrates and other nitric oxide donors as absolute contraindications.

A sharp drop in blood pressure: dizziness, visual greying, reflex tachycardia, cold sweat, syncope. In patients with ischaemic heart disease the collapse of coronary perfusion pressure threatens myocardial infarction. Because the dinitrate is long-acting, hypotension can be prolonged and return in waves as the extended-release form keeps releasing nitrate.

The combination is not prescribed in any form. In a patient on maintenance isosorbide dinitrate, extended-release forms included, vardenafil is contraindicated; the labels give no safe interval for that scenario, and after stopping an extended-release form the nitrate keeps working for hours. After the last dose of vardenafil, wait at least 24 hours before any nitrate, the same as for sildenafil and half the 48 hours required for tadalafil. If angina strikes before that window closes, withhold the dinitrate: use morphine, oxygen and urgent angiography, with furosemide an option for preload reduction. When choosing an alternative, remember vardenafil's second quirk, QT prolongation: it is not combined with class IA and III antiarrhythmics (quinidine, procainamide, amiodarone, sotalol).