Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2D6 may increase the plasma concentrations of topical sofpironium, which has been shown to be partially metabolized by the isoenzyme. In a pharmacokinetic study in patients with primary axillary hyperhidrosis, sofpironium systemic exposure (AUC) and peak plasma concentration (Cmax) increased approximately 2-fold following concomitant use with the potent CYP450 2D6 inhibitor paroxetine at a 20 mg oral dose. Clinical data for sofpironium use in combination with other less potent CYP450 2D6 inhibitors are not available.

MANAGEMENT: Caution is advised when sofpironium topical is used concurrently with CYP450 2D6 inhibitors. Patients should be more closely monitored for adverse effects such as blurred vision, urinary retention, difficulty controlling body temperature in warm environments, and dry mouth.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of sertraline. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, limited clinical data suggest that consumption of grapefruit juice during treatment with sertraline may result in increased plasma concentrations of sertraline. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism by certain compounds present in grapefruit. An in-vitro study demonstrated that grapefruit juice dose-dependently inhibits the conversion of sertraline to its metabolite, desmethylsertraline. In a study with eight Japanese subjects, mean plasma levels of sertraline increased by approximately 100% and maximum plasma concentrations increased by 66% after the ingestion of three 250 mL glasses of grapefruit juice per day for 5 days and administration of a single dose of sertraline 75 mg on the sixth day. In another small study with 5 patients, mean sertraline trough levels increased by 47% after taking sertraline for at least 6 weeks, then taking sertraline with 240 mL grapefruit juice daily for 1 week. The clinical significance is unknown; however, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients receiving sertraline should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how sertraline affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Some authorities recommend that consumption of grapefruit juice should be avoided during sertraline therapy.