Drug Interactions between amoxicillin / clarithromycin / vonoprazan and silodosin

CONTRAINDICATED: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of silodosin, which is primarily metabolized by the isoenzyme. Severe hypotension and priapism may occur. In pharmacokinetic studies, administration of a single 8 mg dose of silodosin with the potent CYP450 3A4 inhibitor ketoconazole 400 mg/day for 4 days resulted in a 3.8-fold increase in silodosin peak plasma concentration (Cmax) and 3.2-fold increase in systemic exposure (AUC). Coadministration of a single 4 mg dose of silodosin with ketoconazole 200 mg/day for 4 days resulted in 3.7- and 2.9-fold increases in silodosin Cmax and AUC, respectively.

MANAGEMENT: Concomitant use of silodosin with potent CYP450 3A4 inhibitors is considered contraindicated. Some authorities recommend avoiding concomitant use of silodosin during and for 2 weeks after treatment with itraconazole.

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of silodosin, which is primarily metabolized by the isoenzyme. In a pharmacokinetic study, administration of a single 8 mg dose of silodosin with the potent CYP450 3A4 inhibitor ketoconazole (400 mg) resulted in a 3.8-fold increase in silodosin peak plasma concentration (Cmax) and a 3.2-fold increase in systemic exposure (AUC). The interaction has not been studied with moderate CYP450 3A4 inhibitors such as diltiazem, erythromycin, and verapamil.

MANAGEMENT: Caution is advised if silodosin is prescribed in combination with inhibitors of CYP450 3A4. Pharmacologic response to silodosin should be monitored more closely whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy, and the silodosin dosage adjusted as necessary. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Taking silodosin at bedtime may minimize the occurrence of orthostatic effects. Patients should also avoid driving or operating hazardous machinery until they know how the medication affects them.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.