Interactions: Tadalafil is a substrate of and predominantly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase tadalafil exposure. So drugs like ketoconazole, ritonavir, erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure and rifampin, carbamazepine, phenytoin, and phenobarbitol, would likely decrease tadalafil exposure. Alcohol and PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. When mild vasodilators are taken in combination, blood-pressure-lowering effects of each individual compound may be increased. Administration of tadalafil to patients, who are using any form of organic nitrate, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates. In a patient who has taken tadalafil, where nitrate administration is deemed medically necessary in a life-threatening situation, at least 48 hours should elapse after the last dose of tadalafil before nitrate administration is considered.