Effects of Other Drugs on CIALIS

Cytochrome P450 Inhibitors

CIALIS is a substrate of and predominantly metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase tadalafil exposure (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Ketoconazole — Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A4, increased tadalafil 20-mg single-dose exposure (AUC) by 312% and Cmaxby 22%, relative to the values for tadalafil 20 mg alone. Ketoconazole (200 mg daily) increased tadalafil10-mg single-dose exposure (AUC) by 107% and Cmax by 15%, relative to the values for tadalafil 10 mg alone.

HIV Protease inhibitor — Ritonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A4, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20-mg single-dose exposure (AUC) by 32% with a 30% reduction in Cmax, relative to the values for tadalafil 20 mg alone. Ritonavir (200 mg twice daily), increased tadalafil 20-mg single-dose exposure (AUC) by 124% with no change in Cmax, relative to the values for tadalafil 20 mg alone. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure (see DOSAGE AND ADMINISTRATION).

Based upon these results, in patients taking concomitant potent CYP3A4 inhibitors, the dose of CIALIS should not exceed 10 mg, and CIALIS should not be taken more frequently than once in every 72 hours (see DOSAGE AND ADMINISTRATION).

Other cytochrome P450 inhibitors — Although specific interactions have not been studied, other CYP3A4 inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure.
Cytochrome P450 Inducers

Studies have shown that drugs that induce CYP3A4 can decrease tadalafil exposure.

Rifampin — Rifampin (600 mg daily), a CYP3A4 inducer, reduced tadalafil 10-mg single-dose exposure (AUC) by 88% and Cmax by 46%, relative to the values for tadalafil 10 mg alone. Although specific interactions have not been studied, other CYP3A4 inducers, such as carbamazepine, phenytoin, and phenobarbital, would likely decrease tadalafil exposure. No dose adjustment is warranted.
Gastrointestinal Drugs

H2 antagonists — An increase in gastric pH resulting from administration of nizatidine had no significant effect on tadalafil pharmacokinetics.

Antacids — Simultaneous administration of an antacid (magnesium hydroxide/aluminum hydroxide) and tadalafil reduced the apparent rate of absorption of tadalafil without altering exposure (AUC) to tadalafil.