Drug Interactions between ethinyl estradiol and lenalidomide

MONITOR CLOSELY: Concomitant treatment with agents that can cause thrombosis such as estrogens 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: The use of estrogen-containing medications including combined oral contraceptive pills should be undertaken with caution in patients receiving lenalidomide, particularly multiple myeloma patients receiving lenalidomide with dexamethasone. Patients should be apprised of the increased risk of venous thromboembolic events if a combined oral contraceptive pill is chosen as one of two effective methods of contraception that must be used simultaneously and continuously for 4 weeks before, during (even in case of dose interruption), and for 4 weeks after lenalidomide therapy. Input from a gynecologist or similar expert on adequate contraception should be sought as needed. Patients should be advised to seek medical attention if they develop potential signs and symptoms of thromboembolism such as chest pain, shortness of breath, and pain or swelling in the arms or legs. 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 an assessment of underlying risk factors. If a thromboembolic event occurs during therapy with lenalidomide, treatment must be discontinued and standard anticoagulation therapy started. 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.