Important Safety Information
WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM
Embryo-Fetal Toxicity
Do not use REVLIMID during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study.
Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may
cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment.
Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after
REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program,
the REVLIMID REMS® program (formerly known as the “RevAssist®” program).
Information about the REVLIMID REMS® program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free
number 1-888-423-5436.
Hematologic Toxicity (Neutropenia and Thrombocytopenia)
REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q myelodysplastic syndrome (MDS) had to have
a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was
seen in 80% of patients enrolled in the study. Patients on therapy for del 5q MDS should have their complete blood counts monitored weekly for the first 8 weeks of
therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support
and/or growth factors.
Venous and Arterial Thromboembolism
REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction
and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of
thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling.
Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient’s underlying risks.
CONTRAINDICATIONS
Pregnancy:
• REVLIMID can cause fetal harm when administered to a pregnant female. Lenalidomide is contraindicated in females who are pregnant. If this drug is used during
pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus
Allergic Reactions:
• REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis)
to lenalidomide
WARNINGS AND PRECAUTIONS
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Embryo-Fetal Toxicity:
• REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects or embryo-fetal death. An embryo-fetal development
study in monkeys indicated 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
• Females of Reproductive Potential: Must avoid pregnancy for at least 4 weeks before beginning REVLIMID therapy, during therapy, during dose interruptions and for at
least 4 weeks after completing therapy. 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 REVLIMID, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of REVLIMID
therapy. Must obtain 2 negative pregnancy tests prior to initiating therapy
• Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with
females of reproductive potential while taking REVLIMID and for up to 28 days after discontinuing REVLIMID, even if they have undergone a successful vasectomy.
Male patients taking REVLIMID must not donate sperm
• Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 1 month following discontinuation of the drug because the blood might be
given to a pregnant female patient whose fetus must not be exposed to REVLIMID
REVLIMID REMS Program
Because of embryo-fetal risk, REVLIMID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) the REVLIMID REMS Program
(formerly known as the “RevAssist®” Program). Prescribers and pharmacies must be certified with the program and patients must sign an agreement form and comply
with the requirements. Further information about the REVLIMID REMS program is available at www.celgeneriskmanagement.com or by telephone at 1-888-423-5436
Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Patients may require dose interruption and/or dose reduction. MCL: Patients
taking REVLIMID for MCL should have their complete blood counts monitored weekly for the first cycle (28 days), every 2 weeks during cycles 2-4, and then monthly
thereafter. 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
Venous and Arterial Thromboembolism: A significantly increased risk of DVT (7.4%) and PE (3.7%) occurred in patients with MM treated with REVLIMID and dex
compared to the placebo and dex group (3.1% and 0.9%) in clinical trials with varying use of anticoagulant therapies. Myocardial infarction (1.7%) and stroke (CVA) (2.3%)
are increased in patients with MM who were treated with REVLIMID and dex therapy compared with placebo and dex (0.6%, and 0.9%) in clinical trials. Patients with known
risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g. hyperlipidemia, hypertension, smoking).
In controlled clinical trials that did not use concomitant thromboprophylaxis, 21.5% overall thrombotic events occurred in patients with refractory and relapsed MM who were
treated with REVLIMID and dex compared to 8.3% thrombosis in the placebo and dex group. Median time to first thrombosis event was 2.7 months. ESAs and estrogens may
further increase the risk of thrombosis and their use should be based on a benefit-risk decision. See Boxed WARNINGS