Drug Interaction Report

MONITOR CLOSELY: Concomitant treatment with agents that can cause thrombosis such as erythropoiesis- or thrombopoiesis-stimulating agents, estrogens, selective estrogen receptor modulators, or C1 esterase inhibitors may potentiate the risk of venous thromboembolic events associated with the use of lenalidomide. Deep vein thrombosis (DVT) and pulmonary embolism (PE) have been observed at significantly increased rates when lenalidomide was coadministered with dexamethasone for the treatment of multiple myeloma. In two clinical trials consisting of a total of 703 multiple myeloma patients, DVT was reported as a serious or Grade 3/4 adverse drug reaction in 7.4% and 8.2% of patients in the lenalidomide/dexamethasone group (n=353), respectively, compared to 3.1% and 3.4% of patients in the placebo/dexamethasone group (n=350), respectively. Likewise, PE was reported as a serious or Grade 3/4 adverse drug reaction in 3.7% of patients in the lenalidomide/dexamethasone group versus 0.9% of patients in the placebo/dexamethasone group. Venous thromboembolic events have also been reported during lenalidomide monotherapy for the treatment of myelodysplastic syndromes.

MANAGEMENT: Agents that are known to cause thrombosis should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone. Patients should be advised to seek medical attention if they develop potential signs and symptoms of thromboembolism such as chest pain; shortness of breath; rapid pulse; pain, swelling, and/or discoloration in an arm or leg; and numbness or weakness on one side of the body. It is not known whether prophylactic anticoagulation or antiplatelet therapy may lessen the risk of venous thromboembolic events. The decision to take prophylactic measures should be done carefully after a thorough assessment of underlying risk factors. If a thromboembolic event occurs during therapy with lenalidomide, treatment must be discontinued and standard anticoagulation therapy initiated. Once anticoagulation is stabilized and complications of the thromboembolic event under control, lenalidomide may be restarted at the original dose if benefit is deemed to outweigh the risks. Anticoagulation therapy should be continued during the remaining course of lenalidomide treatment.

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.