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Clinical Trials

Previously Treated MM

Two randomized studies were conducted to evaluate the efficacy and safety of REVLIMID. These multicenter, multinational, double-blind, placebo-controlled studies compared REVLIMID plus oral pulse high-dose dexamethasone (dex) therapy to dex therapy alone in patients with MM who had received at least one prior treatment.

In both studies, patients in the REVLIMID/dex group took 25 mg of REVLIMID once daily on Days 1-21 of each 28-day cycle. Patients in both treatment groups took 40 mg of dex once daily on Days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy. The dose of dex was reduced to 40 mg once daily on Days 1-4 of each 28-day cycle after the first 4 cycles of therapy. In both studies, treatment was to continue until disease progression.

The primary efficacy endpoint in both studies was time to progression (TTP). TTP was defined as the time from randomization to the first occurrence of progressive disease.

Click on the links below to review TTP and response rates for both studies.

Extended Time to Progression

The primary efficacy endpoint in both studies was time to progression (TTP). TTP was defined as the time from randomization to the first occurrence of progressive disease.

Time To Progression

Significantly superior TTP with REVLIMID/dexamethasone (REV/dex) vs placebo/dex in 2 studies (P<0.001)

  • Median TTP was:
    • Study 1: 13.9 months (95% CI, 9.5-18.5) with REV/dex vs 4.7 months (95% CI, 3.7-4.9) with placebo/dex
    • Study 2: 12.1 months (95% CI, 9.5-NE) with REV/dex vs 4.7 months (95% CI, 3.8-4.8) with placebo/dex
  • Results of 2 randomized, double-blind, placebo-controlled studies comparing REV/dex to placebo/dex in patients who had received at least 1 prior treatment. TTP, time from randomization to the first occurrence of disease progression based on the myeloma response criteria developed by Bladé, et al., treatment discontinuation due to disease progression according to the investigator (whether or not confirmed by the Bladé, et al. criteria), or death due to disease progression while on treatment. (TTP was measured to the date of last visit or to death if death occurred on or before treatment discontinuation)1,2
  • TTP was based on data up to cutoff (June 7, 2005, for Study 1; August 3, 2005, for Study 2)

Overall Response Rate

More than doubled response rates

Study 1-2 Response Rates

Overall response (OR) rates were >50% with REVLIMID/dexamethasone (REV/dex) vs ≤23% with placebo/dex

  • Complete response (CR) rates were:
    • Study 1: 13% (23/177) with REV/dex vs 1% (1/176) with placebo/dex
    • Study 2: 15% (27/176) with REV/dex vs 4% (7/175) with placebo/dex
  • Partial response (PR) rates were:
    • Study 1: 48% (84/177) with REV/dex vs 19% (33/176) with placebo/dex
    • Study 2: 44% (77/176) with REV/dex vs 19% (34/175) with placebo/dex
  • Results of 2 randomized, double-blind, placebo-controlled studies comparing REV/dex to placebo/dex in patients who had received at least 1 prior treatment.
    OR = CR + PR. CR based on EBMT/IBMTR/ABMTR criteria.1,2 PR based on modified EBMT/IBMTR/ABMTR criteria, modifications as follows1:
    • 50%-74% reduction in level of serum monoclonal paraprotein, maintained for a minimum of 6 weeks (vs ≥50% reduction in EBMT/IBMTR/ABMTR criteria)
    • If present, 50%-89% reduction from baseline in 24-hour urinary light chain excretion by electrophoresis, maintained for a minimum of 6 weeks (vs ≥90% reduction or to <200 mg, maintained for 6 weeks in EBMT/IBMTR/ABMTR criteria)
    • If present, no clear progression of evaluable soft tissue plasmacytomas or non-evaluable disease (vs ≥50% reduction in the size of soft tissue plasmacytomas in EBMT/IBMTR/ABMTR criteria)
    • No evidence of disease progression by bone marrow aspirate/biopsy findings (vs for patients with nonsecretory myeloma only, ≥50% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, for a minimum of 6 weeks in EBMT/IBMTR/ABMTR criteria)
  • Based on data up to cutoff (June 7, 2005, for Study 1; August 3, 2005, for Study 2)

Important Risk Information

  • Most adverse events and Grade 3/4 adverse events were more frequent in patients who received the combination of REVLIMID/dexamethasone (REV/dex) compared to placebo/dex
  • In the pooled multiple myeloma studies, Grade 3/4 hematologic toxicities were more frequent in patients treated with the combination of REV/dex than in patients treated with placebo/dex
  • Grade 3/4 neutropenia occurred in 33.4% of patients treated with REV/dex vs 3.4% of patients treated with placebo/dex; 2.3% of patients treated with REV/dex experienced Grade 3/4 febrile neutropenia vs 0% with placebo/dex
  • Deep vein thrombosis (DVT) was reported as a serious adverse drug reaction (7.4%) or Grade 3/4 (8.2%) at a higher rate in the REV/dex group compared to 3.1% and 3.4% in the placebo/dex group, respectively. Discontinuations due to DVT adverse reactions were reported at comparable rates between groups
  • Pulmonary embolism (PE) was reported as a serious adverse drug reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the REV/dex group compared to 0.9% and 0.9% in the placebo/dex group, respectively. Discontinuations due to PE adverse reactions were reported at comparable rates between groups
  • Grade 3/4 adverse events reported in ≥5% of patients: neutropenia (33.4%/3.4%), thrombocytopenia (12.2%/6.3%), anemia (9.9%/5.7%), pneumonia (8.5%/5.4%), DVT (8.2%/3.4%), fatigue (6.5%/4.9%), and muscle weakness (5.7%/2.9%)
  • 76% (269/353) of patients in the REV/dex arm required at least 1 dose interruption/reduction vs 57% (199/350) in the placebo/dex arm. Of these patients, 50% of patients in the REV/dex arm required at least 1 additional dose interruption/reduction vs 21% in the placebo/dex arm

Learn more about adverse reactions in patients with previously treated multiple myeloma.

CBCs, complete blood counts.

Important dosing information

  • Lenalidomide is primarily excreted unchanged by the kidney. Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function
  • Monitor CBCs every 2 weeks for the first 12 weeks, then monthly thereafter
  • Treatment is continued or modified based on clinical and laboratory findings
  • 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
    • Patients may require dose interruption and/or reduction
    • Patients may require the use of blood product support and/or growth factors

Important risk information

  • Most adverse events and Grade 3/4 adverse events were more frequent in patients who received the combination of REV/dex compared to placebo/dex
  • In the pooled multiple myeloma studies, Grade 3/4 hematologic toxicities were more frequent in patients treated with the combination of REV/dex than in patients treated with placebo/dex
  • Grade 3/4 neutropenia occurred in 33.4% of patients treated with REV/dex vs 3.4% of patients treated with placebo/dex; 2.3% of patients treated with REV/dex experienced Grade 3/4 febrile neutropenia vs 0% with placebo/dex
  • Deep vein thrombosis (DVT) was reported as a serious adverse drug reaction (7.4%) or Grade 3/4 (8.2%) at a higher rate in the REV/dex group compared to 3.1% and 3.4% in the placebo/dex group, respectively. Discontinuations due to DVT adverse reactions were reported at comparable rates between groups
  • Pulmonary embolism (PE) was reported as a serious adverse drug reaction (3.7%) or Grade 3/4 (4.0%) at a higher rate in the REV/dex group compared to 0.9% and 0.9% in the placebo/dex group, respectively. Discontinuations due to PE adverse reactions were reported at comparable rates between groups
  • Grade 3/4 adverse events reported in ≥5% of patients: neutropenia (33.4%/3.4%), thrombocytopenia (12.2%/6.3%), anemia (9.9%/5.7%), pneumonia (8.5%/5.4%), DVT (8.2%/3.4%), fatigue (6.5%/4.9%), and muscle weakness (5.7%/2.9%)
  • 76% (269/353) of patients in the REV/dex arm required at least 1 dose interruption/reduction vs 57% (199/350) in the placebo/dex arm. Of these patients, 50% of patients in the REV/dex arm required at least 1 additional dose interruption/reduction vs 21% in the placebo/dex arm

Learn more about adverse reactions in patients with previously treated multiple myeloma.

CBCs, complete blood counts.

References:
  1. Data on file, Celgene Corporation.
  2. Bladé J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Br J Haematol. 1998;102(5):1115-1123.
Important Safety Information Prescribing Information FDA Contact REV Assist

REVLIMID® (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy.

REVLIMID® (lenalidomide) is indicated for 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.

Important Safety Information

WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

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 death to a developing baby. In women of childbearing potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Women of childbearing potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid fetal exposure to lenalidomide, REVLIMID is only available under a restricted distribution program called "RevAssist®."

Information about the RevAssist program is available at www.REVLIMID.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. (see DOSAGE and ADMINISTRATION)

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who were treated with REVLIMID and dexamethasone therapy. Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID may lessen the potential for venous thromboembolic events. The decision to take prophylactic measures should be done carefully after an assessment of an individual patient’s underlying risk factors.

CONTRAINDICATIONS:

Pregnancy Category X:

  • Lenalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy

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:

Fetal Risk:

  • REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects. An embryofetal development study in non-human primates 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. If REVLIMID is used during pregnancy, it may cause birth defects or death to a developing baby
  • Females of childbearing potential must be advised to avoid pregnancy while on REVLIMID. Two effective contraceptive methods should be used during therapy, during therapy interruptions, and for at least 4 weeks after completing therapy
  • Male Patients: It is not known whether lenalidomide is present in the semen of patients receiving the drug. Therefore, males receiving REVLIMID must always use a latex condom during any sexual contact with females of childbearing potential, even if they have undergone a successful vasectomy

Reproductive Risk and Special Prescribing Requirements (RevAssist® Program):

  • Because of this potential toxicity and to avoid fetal exposure, REVLIMID is only available under a special restricted distribution program called "RevAssist." Prescribers and pharmacists registered with the program can prescribe and dispense the product to patients who are registered and meet all the conditions of the RevAssist® program

Hematologic Toxicity—Multiple Myeloma:

  • REVLIMID can cause significant neutropenia and thrombocytopenia
  • Patients taking REVLIMID for MM should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafter
  • In the pooled MM studies Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID and dexamethasone than in patients treated with dexamethasone alone
  • Patients may require dose interruption and/or dose reduction

Deep Vein Thrombosis:

  • Venous thromboembolic events (predominantly deep venous thrombosis and pulmonary embolism) have occurred in patients with MM treated with lenalidomide combination therapy and patients with MDS treated with lenalidomide monotherapy

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

Tumor Lysis Syndrome:

  • Fatal instances of tumor lysis syndrome have been reported during treatment with lenalidomide. The patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction:

  • Tumor flare reaction has occurred during investigational use of lenalidomide for chronic lymphocytic leukemia (CLL) and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash. Treatment of CLL or lymphoma with lenalidomide outside of a well-monitored clinical trial is discouraged

DRUG INTERACTIONS:

  • Erythropoietic agents, or other agents, that may increase the risk of thrombosis, such as estrogen containing therapies, should be used with caution in MM patients receiving lenalidomide with dexamethasone

USE IN SPECIAL POPULATIONS:

Nursing Mothers:

  • It is not known whether REVLIMID is excreted in human milk
  • Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother

Geriatric Use:

  • Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function

Renal Impairment:

  • Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment (CLcr < 60 mL/min) and in patients on dialysis

ADVERSE REACTIONS:

Multiple Myeloma

  • In the REVLIMID/dexamethasone treatment group, 269 patients (76%) underwent at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group
  • Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group underwent at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group
  • Most adverse events and Grade 3/4 adverse events were more frequent in MM patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone
  • Adverse reactions reported in ≥15% of MM patients (REVLIMID/dexamethasone vs dexamethasone/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), weight decreased (20% vs 15%), nasopharyngitis (18% vs 9%), blurred vision (17% vs 11%), anorexia (16% vs 10%), and dysgeusia (15% vs 10%)

Myelodysplastic Syndromes

  • Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events observed in the del 5q MDS population
  • Other adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): 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%)

DOSAGE AND ADMINISTRATION:

  • Treatment is continued or modified based upon clinical and laboratory findings. Dosing modifications are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID
  • For other Grade 3 or 4 toxicities judged to be related to REVLIMID, hold treatment and restart at next lower dose level when toxicity has resolved to ≤Grade 2

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

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Full Prescribing Information: Contents*

WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

Highlights of Prescribing Information

Boxed Warning

1 Indication and Usage 1.1 Multiple Myeloma 1.2 Myelodysplastic Syndromes

2 Dosage and Administration 2.1 Multiple Myeloma 2.2 Myelodysplastic Syndromes

3 Dosage Forms and Strength

4 Contraindications 4.1 Pregnancy 4.2 Allergic Reactions

5 Warnings and Precautions 5.1 Fetal Risk 5.2 Reproductive Risk and Special Prescribing Requirements 5.3 Hematologic Toxicity
5.4 Deep Vein Thrombosis and Pulmonary Embolism
5.5 Allergic Conditions
5.6 Tumor Lysis Syndrome
5.7 Tumor Flare Reaction

6 Adverse Reactions 6.1 Clinical Trials Experience in Multiple Myeloma 6.2 Clinical Trials Experience in Myelodysplastic Syndromes 6.3 Postmarketing Experience

7 Drug Interactions 7.1 Digoxin 7.2 Warfarin 7.3 Drugs that Increase the Risk of Thrombosis

8 Use in Specific Populations 8.1 Pregnancy 8.2 Nursing Mothers 8.3 Pediatric Use 8.4 Geriatric Use 8.5 Renal Impairment 8.6 Hepatic Impairment

9 Overdosage

10 Description

11 Clinical Pharmacology 11.1 Mechanism of Action 11.3 Pharmacokinetics

12 Nonclinical Toxicology 12.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 12.2 Reproductive and Developmental Toxicity

13 Clinical Studies 13.1 Multiple Myeloma 13.2 Myelodysplastic Syndromes

14 References

15 How Supplied/Storage and Handling

16 Patient Counseling Information 16.1 Importance of Preventing Pregnancy 16.2 Hematologic Toxicity 16.3 Deep Vein Thrombosis and Pulmonary Embolism 16.4 Medication Guide

*Sections or subsections omitted from the full prescribing information are not listed.

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MDS Educational Resources

Download the materials below to learn more about MDS

REVLIMID Resource Myelodysplastic Syndromes (MDS)
Questions and Answers
REVLIMID Resource Living with Myelodysplastic Syndromes
REVLIMID Resource Understanding Your Blood
REVLIMID Resource Understanding Red Blood Cell Transfusions

You must have the free Adobe® Reader® installed on your computer to view these PDF files.

If you do not have Adobe® Reader®, please click on the button below to download it.

Download Adobe Reader

REVLIMID® (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy.

REVLIMID® (lenalidomide) is indicated for 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.

Important Safety Information

WARNING: FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

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 death to a developing baby. In women of childbearing potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Women of childbearing potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid fetal exposure to lenalidomide, REVLIMID is only available under a restricted distribution program called "RevAssist®."

Information about the RevAssist program is available at www.REVLIMID.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. (see DOSAGE and ADMINISTRATION)

DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM
REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with MM who were treated with REVLIMID and dexamethasone therapy. Patients and physicians are advised to be observant for the signs and symptoms of thromboembolism. Patients should be instructed to seek medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID may lessen the potential for venous thromboembolic events. The decision to take prophylactic measures should be done carefully after an assessment of an individual patient’s underlying risk factors.

CONTRAINDICATIONS:

Pregnancy Category X:

  • Lenalidomide is contraindicated in pregnant women and women capable of becoming pregnant. Females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy

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:

Fetal Risk:

  • REVLIMID is an analogue of thalidomide, a known human teratogen that causes life-threatening human birth defects. An embryofetal development study in non-human primates 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. If REVLIMID is used during pregnancy, it may cause birth defects or death to a developing baby
  • Females of childbearing potential must be advised to avoid pregnancy while on REVLIMID. Two effective contraceptive methods should be used during therapy, during therapy interruptions, and for at least 4 weeks after completing therapy
  • Male Patients: It is not known whether lenalidomide is present in the semen of patients receiving the drug. Therefore, males receiving REVLIMID must always use a latex condom during any sexual contact with females of childbearing potential, even if they have undergone a successful vasectomy

Reproductive Risk and Special Prescribing Requirements (RevAssist® Program):

  • Because of this potential toxicity and to avoid fetal exposure, REVLIMID is only available under a special restricted distribution program called "RevAssist." Prescribers and pharmacists registered with the program can prescribe and dispense the product to patients who are registered and meet all the conditions of the RevAssist® program

Hematologic Toxicity—Multiple Myeloma:

  • REVLIMID can cause significant neutropenia and thrombocytopenia
  • Patients taking REVLIMID for MM should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafter
  • In the pooled MM studies Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID and dexamethasone than in patients treated with dexamethasone alone
  • Patients may require dose interruption and/or dose reduction

Deep Vein Thrombosis:

  • Venous thromboembolic events (predominantly deep venous thrombosis and pulmonary embolism) have occurred in patients with MM treated with lenalidomide combination therapy and patients with MDS treated with lenalidomide monotherapy

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

Tumor Lysis Syndrome:

  • Fatal instances of tumor lysis syndrome have been reported during treatment with lenalidomide. The patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction:

  • Tumor flare reaction has occurred during investigational use of lenalidomide for chronic lymphocytic leukemia (CLL) and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash. Treatment of CLL or lymphoma with lenalidomide outside of a well-monitored clinical trial is discouraged

DRUG INTERACTIONS:

  • Erythropoietic agents, or other agents, that may increase the risk of thrombosis, such as estrogen containing therapies, should be used with caution in MM patients receiving lenalidomide with dexamethasone

USE IN SPECIAL POPULATIONS:

Nursing Mothers:

  • It is not known whether REVLIMID is excreted in human milk
  • Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother

Geriatric Use:

  • Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function

Renal Impairment:

  • Since REVLIMID is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment (CLcr < 60 mL/min) and in patients on dialysis

ADVERSE REACTIONS:

Multiple Myeloma

  • In the REVLIMID/dexamethasone treatment group, 269 patients (76%) underwent at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group
  • Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group underwent at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group
  • Most adverse events and Grade 3/4 adverse events were more frequent in MM patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone
  • Adverse reactions reported in ≥15% of MM patients (REVLIMID/dexamethasone vs dexamethasone/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), weight decreased (20% vs 15%), nasopharyngitis (18% vs 9%), blurred vision (17% vs 11%), anorexia (16% vs 10%), and dysgeusia (15% vs 10%)

Myelodysplastic Syndromes

  • Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events observed in the del 5q MDS population
  • Other adverse events reported in ≥15% of del 5q MDS patients (REVLIMID): 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%)

DOSAGE AND ADMINISTRATION:

  • Treatment is continued or modified based upon clinical and laboratory findings. Dosing modifications are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID
  • For other Grade 3 or 4 toxicities judged to be related to REVLIMID, hold treatment and restart at next lower dose level when toxicity has resolved to ≤Grade 2

Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.