Interactions between tadalafil and Isordil (isosorbide dinitrate)
isosorbide dinitrate and tadalafil (Major Drug-Drug)
CONTRAINDICATED: Phosphodiesterase-5 (PDE5) inhibitors may potentiate the hypotensive effect of organic nitrates. Significant hypotension may result from use of the combination. The mechanism involves peripheral vasodilation secondary to enhanced levels of cyclic guanosine monophosphate (cGMP) in vascular smooth muscle cells, as PDE5 inhibitors prevent degradation of cGMP while nitrates promote its synthesis. Single oral doses of the PDE5 inhibitors sildenafil (100 mg) and vardenafil (20 mg) have produced mean maximum decreases in supine blood pressure (systolic/diastolic) of approximately 8.4/5.5 and 7/8 mmHg, respectively, compared to placebo. The decrease in blood pressure was most notable approximately 1 to 2 hours after sildenafil dosing and 1 to 4 hours after vardenafil dosing and was additive with that produced by nitrates. Tadalafil 20 mg administered to healthy male subjects produced no significant difference in supine or standing blood pressure compared to placebo, although the drug did potentiate the hypotensive effect of nitrates at a dosage of 5 to 20 mg.
MANAGEMENT: The use of PDE5 inhibitors by patients receiving organic nitrates or other nitric oxide donors, either regularly or intermittently, is considered contraindicated. A suitable time interval following administration of sildenafil or vardenafil for the safe administration of nitrates has not been determined. For tadalafil, data from a clinical pharmacology study suggest that at least 48 hours should elapse after the last dose of tadalafil before nitrate administration is considered should it be deemed medically necessary in a life-threatening situation. Even then, nitrates should still only be administered under close medical supervision with appropriate hemodynamic monitoring.
