lenalidomide

Important safety information

Increased Mortality: serious and fatal cardiac adverse reactions occurred in patients with CLL treated with lenalidomide capsules ( 5.5 ). Second Primary Malignancies (SPM): Higher incidences of SPM were observed in controlled trials of patients with MM receiving lenalidomide ( 5.6 ). Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue ( 5.7 ). Hepatotoxicity: Hepatic failure including fatalities; monitor liver function. Stop lenalidomide capsules and evaluate if hepatotoxicity is suspected ( 5.8 ). Severe Cutaneous Reactions: Discontinue lenalidomide capsules for severe reactions ( 5.9 ). Tumor lysis syndrome (TLS) including fatalities: Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions ( 5.10 ). Tumor flare reaction: Serious tumor flare reactions, including fatal reactions, have occurred during investigational use of lenalidomide for chronic lymphocytic leukemia and lymphoma ( 5.11 ). Impaired Stem Cell mobilization: A decrease in the number of CD34+ cells collected after treatment (> 4 cycles) with lenalidomide has been reported. Consider early referral to transplant center ( 5.12 ). Early mortality in MCL: Higher rate of early deaths have occurred in patients with MCL ( 5.14 ). Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue lenalidomide capsules for angioedema and anaphylaxis ( 5.15 ). 5.1 Embryo-Fetal Toxicity Lenalidomide is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes life-threatening human birth defects or embryo-fetal death [see Use in Specific Populations (8.1) ] . An embryo-fetal development study in monkeys indicates that lenalidomide produced malformations in the offspring of female monkeys who received the drug during pregnancy, similar to birth defects observed in humans following exposure to thalidomide during pregnancy. Lenalidomide capsules are only available through the Lenalidomide REMS program [see Warnings and Precautions (5.2) ] . Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning lenalidomide capsules therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, beginning 4 weeks prior to initiating treatment with lenalidomide capsules, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of lenalidomide capsules therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing lenalidomide capsules therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles or every 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3) ] . Males Lenalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking lenalidomide capsules and for up to 4 weeks after discontinuing lenalidomide capsules, even if they have undergone a successful vasectomy. Male patients taking lenalidomide capsules must not donate sperm and for up to 4 weeks after discontinuing lenalidomide capsules [see Use in Specific Populations (8.3) ] . Blood Donation Patients must not donate blood during treatment with lenalidomide capsules and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to lenalidomide. 5.2 Lenalidomide REMS Program Because of the embryo-fetal risk [see Warnings and Precautions (5.1) ] , lenalidomide capsules are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the Lenalidomide REMS program. Required components of the Lenalidomide REMS program include the following: Prescribers must be certified with the Lenalidomide REMS program by enrolling and complying with the REMS requirements. Patients must sign a Patient-Physician agreement form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ] and males must comply with contraception requirements [see Use in Specific Populations (8.3) ] . Pharmacies must be certified with the Lenalidomide REMS program, must only dispense to patients who are authorized to receive lenalidomide capsules and comply with REMS requirements. Further information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by telephone at 1-866-604-3268. 5.3 Hematologic Toxicity Lenalidomide can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medication that may increase risk of bleeding. Patients taking lenalidomide capsules should have their complete blood counts assessed periodically as described below [see Dosage and Administration (2.1 , 2.2 , 2.3) ] . Monitor complete blood counts (CBC) in patients taking lenalidomide capsules in combination with dexamethasone or as lenalidomide capsule maintenance therapy for MM every 7 days (weekly) for the first 2 cycles, on Days 1 and 15 of Cycle 3, and every 28 days (4 weeks) thereafter. A dose interruption and/or dose reduction may be required [see Dosage and Administration (2.1) ] . In the MM maintenance therapy trials, Grade 3 or 4 neutropenia was reported in up to 59% of lenalidomide-treated patients and Grade 3 or 4 thrombocytopenia in up to 38% of lenalidomide-treated patients [see Adverse Reactions (6.1) ] . Monitor complete blood counts (CBC) in patients taking lenalidomide capsule for MDS weekly for the first 8 weeks and at least monthly thereafter. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the MDS study. In the 48% of patients who developed Grade 3 or 4 neutropenia, the median time to onset was 42 days (range, 14-411 days), and the median time to documented recovery was 17 days (range, 2-170 days). In the 54% of patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was 28 days (range, 8-290 days), and the median time to documented recovery was 22 days (range, 5-224 days) [see Boxed Warning and Dosage and Administration (2.2) ] . Monitor complete blood counts (CBC) in patients taking lenalidomide capsule for MCL weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction. In the MCL trial, Grade 3 or 4 neutropenia was reported in 43% of the patients. Grade 3 or 4 thrombocytopenia was reported in 28% of the patients. Monitor complete blood counts (CBC) in patients taking lenalidomide capsule for FL or MZL weekly for the first 3 weeks of Cycle 1 (28 days), every 2 weeks during Cycles 2-4, and then monthly thereafter. Patients may require dose interruption and/or dose reduction. In the AUGMENT and MAGNIFY trials, Grade 3 or 4 neutropenia was reported in 50% and 33%, respectively, of patients in the lenalidomide capsule/rituximab arm. Grade 3 or 4 thrombocytopenia was reported in 2% and 8%, respectively, of patients in the lenalidomide capsule/rituximab arm [see Adverse Reactions (6.1) ] . 5.4 Venous and Arterial Thromboembolism Venous thromboembolic events (VTE [DVT and PE]) and arterial thromboembolic events (ATE, myocardial infarction and stroke) are increased in patients…