Comment
Author: Admin | 2025-04-28
C) [see Dosage and Administration (2.2) and Warnings and Precautions (5.4)]. Patients with diabetes mellitus In male patients with diabetes mellitus after a 10 mg tadalafil dose, exposure (AUC) was reduced approximately 19% and C max was 5% lower than that observed in healthy subjects. No dose adjustment is warranted. Race Pharmacokinetic studies have included subjects from different ethnic groups, and no differences in the typical exposure to tadalafil have been identified. No dose adjustment is warranted. Gender In healthy female and male subjects following single and multiple-doses of tadalafil, no clinically relevant differences in exposure (AUC and C max) were observed. No dose adjustment is warranted. Drug interaction studies Tadalafil is a substrate of and predominantly metabolized by CYP3A. Drugs that inhibit CYP3A can increase tadalafil exposure. Ritonavir Ritonavir (500 mg or 600 mg twice daily at steady state), an inhibitor of CYP3A, CYP2C9, CYP2C19, and CYP2D6, increased tadalafil 20–mg single-dose exposure (AUC) by 32% with a 30% reduction in C max, 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 C max, relative to the values for tadalafil 20 mg alone. Ritonavir inhibits and induces CYP3A, the enzyme involved in the metabolism of tadalafil, in a time-dependent manner. The results suggest the initial inhibitory effect of ritonavir on CYP3A may be mitigated by a more slowly evolving induction effect so that after about 1 week of ritonavir twice daily, the exposure of tadalafil is similar in the presence of and absence of ritonavir [see Dosage and Administration (2.2), Warnings and Precautions (5.2), and Drug Interactions (7.2)]. Although specific interactions have not been studied, other HIV protease inhibitors would likely increase tadalafil exposure. Other Cytochrome P450 inhibitors CYP3A (e.g., ketoconazole) — Ketoconazole (400 mg daily), a selective and potent inhibitor of CYP3A, increased tadalafil 20 mg single-dose exposure (AUC) by 312% and C max by 22%, relative to the values for tadalafil 20 mg alone. Ketoconazole (200 mg daily) increased tadalafil 10–mg single-dose exposure (AUC) by 107% and C max by 15%, relative to the values for tadalafil 10 mg alone. Although specific interactions have not been studied, other CYP3A inhibitors, such as erythromycin, itraconazole, and grapefruit juice, would likely increase tadalafil exposure. Cytochrome P450 inducers CYP3A (e.g., rifampin, bosentan) — Rifampin (600 mg daily), a CYP3A inducer, reduced tadalafil 10 mg single-dose exposure (AUC) by 88% and C max by 46%, relative to the values for tadalafil 10 mg alone. Bosentan (125 mg twice daily), a substrate of CYP2C9 and CYP3A and a moderate inducer of CYP3A, CYP2C9 and possibly CYP2C19, reduced tadalafil (40 mg once per day) systemic exposure by
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