Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of tadalafil, which is primarily metabolized by the isoenzyme. Rifampin (600 mg daily), a potent CYP450 3A4 inducer, has been reported to decrease tadalafil peak plasma concentration (Cmax) and systemic exposure (AUC) from a single 10 mg dose by 46% and 88%, respectively, compared to administration of the drug alone.

MANAGEMENT: Caution is advised if tadalafil is prescribed with CYP450 3A4 inducers. For the treatment of benign prostatic hyperplasia and erectile dysfunction, no dosage adjustment of tadalafil is warranted during coadministration with CYP450 3A4 inducers. However, the possibility of diminished pharmacologic effects of tadalafil should be considered. For the treatment of pulmonary arterial hypertension, concomitant use of tadalafil with patients on chronic potent CYP450 3A4 inducer therapy is not recommended. The manufacturer of the combination therapy macitentan-tadalafil (Opsynvi), also advises against their concomitant use.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MONITOR: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

MANAGEMENT: Caution is recommended with concurrent consumption of large amounts of alcohol in patients taking tadalafil as it may increase the potential for orthostatic signs and symptoms, such as increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.