Drug Interaction Report

MONITOR CLOSELY: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), have occurred during treatment with carfilzomib, and concurrent use of other agents also associated with this adverse effect can potentiate the risk. In clinical trials, the reported incidence of venous thromboembolic events was up to 15.3% with carfilzomib plus lenalidomide and dexamethasone versus 9% with lenalidomide and dexamethasone. In addition, the reported incidence of venous thromboembolic events was up to 10.6% with carfilzomib plus dexamethasone versus 3.1% with bortezomib plus dexamethasone. The incidence of thromboembolic events was 2% with carfilzomib monotherapy.

MANAGEMENT: Caution is advised when carfilzomib is used with other drugs that can increase the risk of thrombosis. Thromboprophylaxis should be considered according to local treatment protocols. Close monitoring for thromboembolic events is recommended in patients with known risk factors (e.g., prior thrombosis, hyperlipidemia, hypertension, smoking) for thromboembolism. Patients should be advised to seek immediate medical attention if they develop symptoms of thromboembolism, such as shortness of breath, chest pain, hemoptysis, or arm or leg swelling or pain.

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.