ation of lenalidomide with other myelosuppressive agents should be undertaken with caution.
Renal impairment Lenalidomide is substantially excreted by the kidney. Therefore care should be taken in dose selection and monitoring of renal function is advised in patients with renal impairment (See Adult Dosage). Thyroid function Cases of hypothyroidism have been reported and monitoring of thyroid function should be considered.
Peripheral neuropathy Lenalidomide is structurally related to thalidomide, which is known to induce severe peripheral neuropathy.
At this time, the neurotoxic potential of lenalidomide associated with long-term use cannot be ruled out.
Tumour Lysis Syndrome Because lenalidomide has anti-neoplastic activity the complications of tumour lysis syndrome may occur. The patients at risk of tumour lysis syndrome are those with high tumour burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. Lactose intolerance Revlimid capsules contain lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Unused capsules Patients should be advised never to give this medicinal product to another person and to return any unused capsules to their pharmacist at the end of the treatment.
Interactions
Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as hormone replacement therapy, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone (See Special Precautions and Adverse Reactions). Oral contraceptives No interaction study has been performed with oral contraceptives. Dexamethasone is known to be a weak to moderate inducer of CYP3A4 and is likely to also affect other enzymes as well as transporters. It may not be excluded that the efficacy of oral contraceptives may be reduced during treatment. Effective measures to avoid pregnancy must be taken (See Special Precautions and Interactions). Results from human in vitro metabolism studies indicate that lenalidomide is not metabolised by cytochrome P450 enzymes suggesting that administration of lenalidomide with drugs that inhibit cytochrome P450 enzymes is not likely to result in metabolic drug interactions in man. In vitro studies indicate that lenalidomide has no inhibitory effect on CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A. Warfarin Co-administration of multiple doses of 10 mg of lenalidomide had no effect on the single dose pharmacokinetics of R- and S- warfarin. Co-administration of a single 25 mg dose of warfarin had no effect on the pharmacokinetics of lenalidomide. However, it is not known whether there is an interaction during clinical use (concomitant treatment with dexamethasone). Dexamethasone is a weak to moderate enzyme inducer and its effect on warfarin is unknown. Close monitoring of warfarin concentration is advised during the treatment. Digoxin Concomitant administration with lenalidomide 10 mg/day increased the plasma exposure of digoxin (0.5 mg, single dose) by 14% with a 90% CI (confidence interval) [0.52%-28.2%]. It is not known whether the effect will be different in the therapeutic situation (higher lenalidomide doses and concomitant treatment with dexamethasone). Therefore, monitoring of the digoxin concentration is advised during lenalidomide treatment. Pregnancy and lactation: Pregnancy (
