Drug Interaction Report

ADJUST DOSE: Concomitant use of avatrombopag with moderate to potent dual inducers of CYP450 2C9 and 3A4 may decrease the systemic exposure (AUC) of avatrombopag which may lead to reduced efficacy. An open-label study evaluated the pharmacokinetic and pharmacodynamic drug-drug interactions of avatrombopag in combination with dual or selective CYP450 2C9 and 3A4 interacting drugs. Administration of a single 20 mg dose of avatrombopag to healthy subjects (n=48) who had achieved steady-state concentrations of rifampin (a moderate CYP450 2C9 and potent CYP450 3A4 inducer) resulted in a 43% reduction in avatrombopag AUC, and a shortened terminal elimination phase half-life from 20.3 hours to 9.84 hours. However, no impact on the maximum platelet count was observed.

MANAGEMENT: For the treatment of patients with chronic immune thrombocytopenia, the manufacturer recommends an increased starting dose of avatrombopag 40 mg orally once daily when used concomitantly with a moderate to potent dual CYP450 2C9 and 3A4 inducer. In patients already receiving avatrombopag therapy and starting a moderate or strong dual CYP450 2C9 and 3A4 inducer, platelet counts should be monitored and avatrombopag dose adjusted according to the manufacturer's product labeling as necessary. Dose adjustments are not recommended when prescribed for the treatment of thrombocytopenia in adult patients with chronic liver disease undergoing a procedure.

ADJUST DOSING INTERVAL: Food reduces the variability in oral absorption and bioavailability of avatrombopag. According to the product labeling, avatrombopag peak plasma concentration (Cmax) and systemic exposure (AUC) were not affected when administered with either a low-fat (500 calories; 3 g fat, 15 g proteins, 108 g carbohydrates) or high-fat (918 calories; 59 g fat, 39 g proteins, 59 g carbohydrates) meal. However, the variability of avatrombopag exposure was reduced by 40% to 60% with food, and the time to reach Cmax was delayed by 0 to 2 hours relative to the fasted state.

MANAGEMENT: To ensure consistent absorption and plasma drug levels, avatrombopag should be taken with food.