In vivo studies: Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma sildenafil concentrations when coadministered with VIAGRA (50 mg) to healthy volunteers. When a single 100 mg dose of VIAGRA was administered with erythromycin, a specific CYP3A4 inhibitor, at steady state (500 mg bid for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC). In addition, in a study performed in healthy male volunteers, coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200 mg tid) with VIAGRA (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC. VIAGRA had no effect on saquinavir pharmacokinetics. Stronger CYP3A4 inhibitors such as ketoconazole or itraconazole would be expected to have still greater effects, and population data from patients in clinical trials did indicate a reduction in sildenafil clearance when it was coadministered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine) (see DOSAGE AND ADMINISTRATION). In another study in healthy male volunteers, coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg bid) with VIAGRA (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is consistent with ritonavir's marked effects on a broad range of P450 substrates. VIAGRA had no effect on ritonavir pharmacokinetics (see DOSAGE AND ADMINISTRATION). Although the interaction between other protease inhibitors and sildenafil has not been studied, their concomitant use is expected to increase sildenafil levels. It can be expected that concomitant administration of CYP3A4 inducers, such as rifampin, will decrease plasma levels of sildenafil. Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of VIAGRA. | ||||
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