REVLIMID® (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM)
REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of
controlled clinical trials
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 1-888423-5436.
Hematologic Toxicity (Neutropenia and Thrombocytopenia)
REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q 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 and 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
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 indicates that lenalidomide produced
malformations in offspring of female monkeys who received 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. 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
f orm 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. Monitor patients with neutropenia for signs of infection. Advise
patients to observe for bleeding or bruising, especially with use of concomitant
medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex
should have their complete blood counts (CBC) assessed every 7 days for the first 2
cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter.
Venous and Arterial Thromboembolism: Venous thromboembolic events (DVT
and PE) and arterial thromboses are increased in patients treated with REVLIMID. A
significantly increased risk of DVT (7.4%) and PE (3.7%) occurred in patients with MM
after at least one prior therapy, treated with REVLIMID/dex compared to placebo/dex
(3.1% and 0.9%) in clinical trials with varying use of anticoagulant therapies. In NDMM
study, in which nearly all patients received antithrombotic prophylaxis, DVT (3.6%) and
PE (3.8%) were reported in the Rd continuous arm. Myocardial infarction (MI, 1.7%)
and stroke (CVA, 2.3%) are increased in patients with MM after at least 1 prior therapy
who were treated with REVLIMID/dex therapy compared with placebo/dex (0.6%, and
0.9%) in clinical trials. In NDMM study, MI (including acute) was reported (2.3%) in the
Rd Continuous arm. Frequency of serious adverse reactions of CVA was (0.8%) in the
Rd Continuous arm. 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/dex compared to
8.3% thrombosis in the placebo/dex group. Median time to first thrombosis event
was 2.8 months. In NDMM study, which nearly all patients received antithrombotic
prophylaxis, overall frequency of thrombotic events was 17.4% in combined Rd
Continuous and Rd18 arms. Median time to first thrombosis event was 4.37 months.
Thromboprophylaxis is recommended and regimen is based on patients underlying
risks. ESAs and estrogens may further increase the risk of thrombosis and their use
should be based on a benefit-risk decision. See Boxed WARNINGS
Increased Mortality in Patients With CLL: In a clinical trial in the first line
treatment of patients with CLL, single agent REVLIMID therapy increased the risk of
death as compared to single agent chlorambucil. In an interim analysis, there were
34 deaths among 210 patients on the REVLIMID treatment arm compared to 18
deaths among 211 patients in the chlorambucil treatment arm, and hazard ratio for
overall survival was 1.92 [95% CI: 1.08-3.41] consistent with a 92% increase in
risk of death. Serious adverse cardiovascular reactions, including atrial fibrillation,
myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID