Drug Interactions between mibefradil and tadalafil

Consumer information for this interaction is not currently available.

ADJUST DOSE: Coadministration with drugs that are potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of tadalafil, which is primarily metabolized by the isoenzyme. According to the product labeling for tadalafil, ketoconazole (400 mg daily), a selective and potent inhibitor of CYP450 3A4, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of a single 20 mg dose of tadalafil by 22% and 312%, respectively, compared to administration of tadalafil alone. Ketoconazole (200 mg daily) increased the Cmax and AUC of a single 10 mg dose of tadalafil by 15% and 107%, respectively. Ritonavir (200 mg twice a day), another potent inhibitor of CYP450 3A4, increased the AUC of a single 20 mg dose of tadalafil by 124% with no change in Cmax.

MANAGEMENT: Concomitant use of tadalafil with potent 3A4 inhibitors is not recommended in patients being treated for pulmonary arterial hypertension or for benign prostatic hyperplasia (BPH). In addition, some authorities recommend avoiding concomitant use of tadalafil during and for 2 weeks after treatment with itraconazole in patients with pulmonary arterial hypertension. For erectile dysfunction, tadalafil labeling recommends that the dosage not exceed 10 mg once every 72 hours when taken on an as needed basis in patients treated concomitantly with a potent CYP450 3A4 inhibitor. When taken on a daily basis, the dose should not exceed 2.5 mg per day. Patients should be advised to promptly notify their physician if they experience pain or tightness in the chest or jaw, irregular heartbeat, nausea, shortness of breath, visual disturbances, syncope, or prolonged erection (greater than 4 hours).