See Full Prescribing Information

This site is
intended for
US audiences only.

REVLIMID® (lenalidomide) capsules for the treatment of multiple myeloma

Hematologic adverse events should be expected with REVLIMID in del 5q MDS

Incidence of hematologic adverse events occurring in ≥5% of all patients who received at least 1 dose of REVLIMID (N=148)

Adverse events All grades
n (%)
Grade 3/4
n (%)
Neutropenia 87 (59) 79 (53)
Febrile neutropenia 8 (5) 6 (4)
Thrombocytopenia 91 (62) 74 (50)
Anemia 17 (12) 9 (6)
Leukopenia 12 (8) 8 (5)
  • Grade 3 and 4 adverse events reported in ≥5% of patients with del 5q MDS, regardless of causality to drug, were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
  • Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study
  • Thrombocytopenia (61.5%; 91/148) and neutropenia (58.5%; 87/148) were the most frequently reported adverse events
  • 80% (118/148) of patients with del 5q MDS had to have a dose interruption/reduction
  • 34% (50/148) of patients had to have a second dose interruption/reduction
  • 54% of patients developed Grade 3 or 4 thrombocytopenia
  • Median time to onset was 28 days (range: 8-290 days)
  • Median time to recovery was 22 days (range: 5-224 days)
  • 48% of patients developed Grade 3 or 4 neutropenia
  • Median time to onset was 42 days (range: 14-411 days)
  • Median time to recovery was 17 days (range: 2-170 days)
  • Febrile neutropenia (all grades) was reported in 5% (8/148) of all patients; Grade 3/4 febrile neutropenia was reported in 4% (6/148) of all patients
  • G-CSF was permitted for patients who developed neutropenia or fever associated with neutropenia
  • Dose modification guidelines are recommended to manage Grade 3/4 neutropenia or thrombocytopenia, or other Grade 3/4 toxicity judged to be related to lenalidomide
  • Venous thromboembolic events (predominantly DVT and PE) have occurred in patients with MDS treated with lenalidomide monotherapy
  • Allergic reactions including hypersensitivity, angioedema, Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) were reported and may in some cases be fatal
  • Fatal instances of Tumor Lysis Syndrome (TLS) have been reported during lenalidomide treatment. Patients at risk of TLS (ie, those with high tumor burden before treatment) should be monitored closely and appropriate precautions taken

Summary of Adverse Events Reported in ≥5% of the REVLIMID Treated Patients in Del 5q MDS Clinical Study

Adverse events 10 mg (N=148)
n (%)
Patients with ≥1 adverse event 148 (100.0)
Thrombocytopenia 91 (61.5)
Neutropenia 87 (58.8)
Diarrhea 72 (48.6)
Pruritus 62 (41.9)
Rash 53 (35.8)
Fatigue 46 (31.1)
Nausea 35 (23.6)
Constipation 35 (23.6)
Nasopharyngitis 34 (23.0)
Arthralgia 32 (21.6)
Pyrexia 31 (20.9)
Back Pain 31 (20.9)
Edema Peripheral 30 (20.3)
Headache 29 (19.6)
Dizziness 29 (19.6)
Cough 29 (19.6)
Muscle Cramp 27 (18.2)
Dyspnea 25 (16.9)
Pharyngitis 23 (15.5)
Upper Respiratory Tract Infection 22 (14.9)
Epistaxis 22 (14.9)
Asthenia 22 (14.9)
Dry Skin 21 (14.2)
Abdominal Pain 18 (12.2)
Pneumonia 17 (11.5)
Anemia 17 (11.5)
Urinary Tract Infection 16 (10.8)
Pain in Limb 16 (10.8)
Hypokalemia 16 (10.8)
Vomiting 15 (10.1)
Insomnia 15 (10.1)
Edema 15 (10.1)
Anorexia 15 (10.1)
Myalgia 13 (8.8)
Sinusitis 12 (8.1)
Peripheral Swelling 12 (8.1)
Night Sweats 12 (8.1)
Leukopenia 12 (8.1)
Contusion 12 (8.1)
Alanine Aminotransferase Increased 12 (8.1)
Abdominal Pain Upper 12 (8.1)
Sweating Increased 10 (6.8)
Rhinitis 10 (6.8)
Pain 10 (6.8)
Hypoesthesia 10 (6.8)
Dysuria 10 (6.8)
Dyspnea Exertional 10 (6.8)
Dry Mouth 10 (6.8)
Acquired Hypothyroidism 10 (6.8)
Rigors 9 (6.1)
Loose Stools 9 (6.1)
Hypomagnesemia 9 (6.1)
Hypertension 9 (6.1)
Dysgeusia 9 (6.1)
Bronchitis 9 (6.1)
Peripheral Neuropathy 8 (5.4)
Palpitations 8 (5.4)
Febrile Neutropenia 8 (5.4)
Erythema 8 (5.4)
Ecchymosis 8 (5.4)
Depression 8 (5.4)
Chest Pain 8 (5.4)
Cellulitis 8 (5.4)

Most Frequently Observed Grade 3 and 4 Adverse Events Regardless of Relationship to Study Drug Treatment in Del 5q MDS Clinical Trial

Adverse events 10 mg (N=148)
n (%)
Patients with ≥1 Grade 3 or 4 adverse event 131 (88.5)
Neutropenia 79 (53.4)
Thrombocytopenia 74 (50.0)
Pneumonia 11 (7.4)
Rash 10 (6.8)
Anemia 9 (6.1)
Leukopenia 8 (5.4)
Fatigue 7 (4.7)
Dyspnea 7 (4.7)
Back Pain 7 (4.7)
Febrile Neutropenia 6 (4.1)
Nausea 6 (4.1)
Diarrhea 5 (3.4)
Pyrexia 5 (3.4)
Sepsis 4 (2.7)
Dizziness 4 (2.7)
Granulocytopenia 3 (2.0)
Chest Pain 3 (2.0)
Pulmonary Embolism 3 (2.0)
Respiratory Distress 3 (2.0)
Pruritus 3 (2.0)
Pancytopenia 3 (2.0)
Muscle Cramp 3 (2.0)
Respiratory Tract Infection 2 (1.4)
Upper Respiratory Tract Infection 2 (1.4)
Asthenia 2 (1.4)
Multi-organ Failure 2 (1.4)
Epistaxis 2 (1.4)
Hypoxia 2 (1.4)
Pleural Effusion 2 (1.4)
Pneumonitis 2 (1.4)
Pulmonary Hypertension 2 (1.4)
Vomiting 2 (1.4)
Sweating Increased 2 (1.4)
Arthralgia 2 (1.4)
Pain in Limb 2 (1.4)
Headache 2 (1.4)
Syncope 2 (1.4)

WARNINGS AND PRECAUTIONS (cont’d)

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose; risk-benefit of treatment should be evaluated in patients with lactose intolerance

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤ Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

NEXT: Dosing of REVLIMID

Indication

REVLIMID® (lenalidomide) is indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1–risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

Back to top  

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.

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 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 risk 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: See Boxed WARNINGS

  • Females of Reproductive Potential: See Boxed WARNINGS
  • 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 4 weeks 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 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 REVLIMID

REVLIMID REMS® Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

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. MDS: 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 dose reduction. Please see the Black Box WARNINGS for further information

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. 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). Thromboprophylaxis is recommended and the regimen should be based on patient’s underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

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. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

Allergic Reactions: Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions. REVLIMID capsules contain lactose; risk-benefit of treatment should be evaluated in patients with lactose intolerance

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤ Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician’s discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

ADVERSE REACTIONS

Myelodysplastic Syndromes

  • Grade 3 and 4 adverse events reported in ≥5% of patients with del 5q MDS were neutropenia (53%), thrombocytopenia (50%), pneumonia (7%), rash (7%), anemia (6%), leukopenia (5%), fatigue (5%), dyspnea (5%), and back pain (5%)
  • Adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): thrombocytopenia (61.5%), neutropenia (58.8%), diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), pharyngitis (16%), epistaxis (15%), asthenia (15%), upper respiratory tract infection (15%)

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

  • PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
  • LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID
  • PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
  • RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on creatinine clearance value and in patients on dialysis

Please see full Prescribing Information, including Boxed WARNINGS.

Back to top



Indication

REVLIMID® (lenalidomide) is indicated for the treatment of patients with transfusion-dependent anemia due to

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.