`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`REVLIMID® safely and effectively. See full prescribing information for
`REVLIMID.
`
`REVLIMID (lenalidomide) capsules, for oral use
`Initial U.S. Approval: 2005
`
`
`
`
`WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC
`TOXICITY, and VENOUS and ARTERIAL
`THROMBOEMBOLISM
`See full prescribing information for complete boxed warning.
`EMBRYO-FETAL TOXICITY
`Lenalidomide, a thalidomide analogue, caused limb
`
`abnormalities in a developmental monkey study similar to birth
`defects caused by thalidomide in humans. If lenalidomide is used
`during pregnancy, it may cause birth defects or embryo-fetal
`death.
`Pregnancy must be excluded before start of treatment. Prevent
`pregnancy during treatment by the use of two reliable methods
`of contraception (5.1).
`REVLIMID is available only through a restricted distribution
`program, called the Lenalidomide REMS program (5.2, 17).
`HEMATOLOGIC TOXICITY. REVLIMID can cause significant
`neutropenia and thrombocytopenia (5.3).
`VENOUS AND ARTERIAL THROMBOEMBOLISM
`Significantly increased risk of deep vein thrombosis (DVT) and
`
`pulmonary embolism (PE), as well as risk of myocardial
`infarction and stroke in patients with multiple myeloma
`receiving REVLIMID with dexamethasone. Anti-thrombotic
`prophylaxis is recommended (5.4).
`
`
`--------------------------RECENT MAJOR CHANGES----------------------------
`Warnings and Precautions (5.1, 5.2)
`8/2021
`Warnings and Precautions (5.1, 5.11)
`5/2022
`
`---------------------------INDICATIONS AND USAGE----------------------------
`REVLIMID is a thalidomide analogue indicated for the treatment of adult
`patients with:
` Multiple myeloma (MM), in combination with dexamethasone (1.1).
` MM, as maintenance following autologous hematopoietic stem cell
`transplantation (auto-HSCT) (1.1).
`Transfusion-dependent anemia due to low- or intermediate-1-risk
`myelodysplastic syndromes (MDS) associated with a deletion 5q
`abnormality with or without additional cytogenetic abnormalities (1.2).
` Mantle cell lymphoma (MCL) whose disease has relapsed or progressed
`after two prior therapies, one of which included bortezomib (1.3).
`Previously treated follicular lymphoma (FL), in combination with a
`rituximab product (1.4).
`Previously treated marginal zone lymphoma (MZL), in combination
`with a rituximab product (1.5).
`Limitations of Use:
`
`REVLIMID is not indicated and is not recommended for the treatment
`of patients with chronic lymphocytic leukemia (CLL) outside of
`controlled clinical trials (1.4).
`
`
`
`
`
`
`
`
`-----------------------DOSAGE AND ADMINISTRATION-----------------------
` MM combination therapy: 25 mg once daily orally on Days 1-21 of
`repeated 28-day cycles. (2.1).
` MM maintenance therapy following auto-HSCT: 10 mg once daily
`continuously on Days 1-28 of repeated 28-day cycles (2.1).
` MDS: 10 mg once daily (2.2).
` MCL: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles
`(2.3).
`FL or MZL: 20 mg once daily orally on Days 1-21 of repeated 28-day
`cycles for up to 12 cycles (2.4).
`Renal impairment: Adjust starting dose based on the creatinine
`clearance value (2.6).
`For concomitant therapy doses, see Full Prescribing Information (2.1,
`2.4, 14.1, 14.4).
`
`----------------------DOSAGE FORMS AND STRENGTHS---------------------
`Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg (3).
`
`
`
`
`
`
`
`
`
`Reference ID: 4987961
`
`-------------------------------CONTRAINDICATIONS------------------------------
`
`Pregnancy (Boxed Warning, 4.1, 5.1, 8.1).
`
`Demonstrated severe hypersensitivity to lenalidomide (4.2, 5.9,5.15).
`
`-----------------------WARNINGS AND PRECAUTIONS-----------------------
`
`Increased Mortality: serious and fatal cardiac adverse reactions occurred
`in patients with CLL treated with REVLIMID (5.5).
`Second Primary Malignancies (SPM): Higher incidences of SPM were
`observed in controlled trials of patients with MM receiving REVLIMID
`(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 REVLIMID and evaluate if hepatotoxicity is suspected
`(5.8).
`Severe Cutaneous Reactions: Discontinue REVLIMID 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 REVLIMID 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 REVLIMID 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 REVLIMID for angioedema and anaphylaxis (5.15).
`
`-------------------------------ADVERSE REACTIONS------------------------------
` MM: Most common adverse reactions (≥20%) include diarrhea, fatigue,
`anemia, constipation, neutropenia, leukopenia, peripheral edema,
`insomnia, muscle cramp/spasms, abdominal pain, back pain, nausea,
`asthenia, pyrexia, upper respiratory tract infection, bronchitis,
`nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness,
`decreased appetite, thrombocytopenia, and tremor (6.1).
` MDS: Most common adverse reactions (>15%) include
`thrombocytopenia, neutropenia, diarrhea, pruritus, rash, fatigue,
`constipation, nausea, nasopharyngitis, arthralgia, pyrexia, back pain,
`peripheral edema, cough, dizziness, headache, muscle cramp, dyspnea,
`pharyngitis, and epistaxis (6.1).
`Non-Hodgkin’s Lymphoma (NHL: MCL, FL or MZL): Most common
`adverse reactions (≥15%) included neutropenia, thrombocytopenia,
`anemia, leukopenia, diarrhea, constipation, nausea, fatigue, pyrexia,
`cough, upper respiratory tract infection, and rash (6.1).
`
`To report SUSPECTED ADVERSE REACTIONS contact Celgene
`Corporation at 1-888-423-5436 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`-------------------------------DRUG INTERACTIONS------------------------------
`
`Digoxin: Monitor digoxin plasma levels periodically due to increased
`Cmax and AUC with concomitant REVLIMID therapy (7.1).
`Concomitant use of erythropoietin stimulating agents or estrogen
`containing therapies with REVLIMID may increase the risk of
`thrombosis (7.2).
`
`
`--------------------------USE IN SPECIFIC POPULATIONS---------------------
`
`Lactation: Advise not to breastfeed (8.2).
`
`See 17 for PATIENT COUNSELING INFORMATION and Medication
`Guide
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Revised: 5/2022
`
`

`

`
`
`
`
` 6
`
`7
`
`8
`
`10
`11
`12
`
`13
`
`14
`
`15
`16
`
`
`
`ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2 Postmarketing Experience
`DRUG INTERACTIONS
`7.1 Digoxin
`7.2 Concomitant Therapies That May Increase the Risk of Thrombosis
`7.3 Warfarin
`USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`8.2 Lactation
`8.3 Females and Males of Reproductive Potential
`8.4 Pediatric Use
`8.5 Geriatric Use
`8.6 Renal Impairment
`OVERDOSAGE
`DESCRIPTION
`CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`CLINICAL STUDIES
`14.1 Multiple Myeloma
`14.2 Myelodysplastic Syndromes (MDS) with a Deletion 5q
`Cytogenetic Abnormality
`14.3 Mantle Cell Lymphoma
`14.4 Follicular and Marginal Zone Lymphoma
`REFERENCES
`HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Storage
`16.3 Handling and Disposal
`PATIENT COUNSELING INFORMATION
`
`17
`
`*Sections or subsections omitted from the full prescribing information are not
`listed.
`
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC
`TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM
`1
`INDICATIONS AND USAGE
`
`1.1 Multiple Myeloma
`
`1.2 Myelodysplastic Syndromes
`
`1.3 Mantle Cell Lymphoma
`
`1.4 Follicular Lymphoma
`
`1.5 Marginal Zone Lymphoma
`
`1.6 Limitations of Use
`2
`DOSAGE AND ADMINISTRATION
`2.1 Recommended Dosage for Multiple Myeloma
`2.2 Recommended Dosage for Myelodysplastic Syndromes
`2.3 Recommended Dosage for Mantle Cell Lymphoma
`2.4 Recommended Dosage for Follicular Lymphoma or Marginal Zone
`Lymphoma
`2.5 Dosage Modifications for Non-Hematologic Adverse Reactions
`2.6 Recommended Dosage for Patients with Renal Impairment
`2.7 Administration
`DOSAGE FORMS AND STRENGTHS
`CONTRAINDICATIONS
`4.1 Pregnancy
`4.2 Severe Hypersensitivity Reactions
`WARNINGS AND PRECAUTIONS
`5.1 Embryo-Fetal Toxicity
`5.2 Lenalidomide REMS Program
`5.3 Hematologic Toxicity
`5.4 Venous and Arterial Thromboembolism
`5.5
`Increased Mortality in Patients with CLL
`5.6 Second Primary Malignancies
`5.7
`Increased Mortality in Patients with MM When Pembrolizumab Is
`Added to a Thalidomide Analogue and Dexamethasone
`5.8 Hepatotoxicity
`5.9 Severe Cutaneous Reactions
`5.10 Tumor Lysis Syndrome
`5.11 Tumor Flare Reaction
`5.12 Impaired Stem Cell Mobilization
`5.13 Thyroid Disorders
`5.14 Early Mortality in Patients with MCL
`5.15 Hypersensitivity
`
`3
`4
`
`5
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4987961
`
`2
`
`

`

`FULL PRESCRIBING 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 [see Warnings and Precautions (5.1), and Medication
`Guide (17)]. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program,
`the Lenalidomide REMS program (5.2).
`
`Information about the Lenalidomide REMS program is available at www.lenalidomiderems.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 syndromes
`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 myelodysplastic
`syndromes 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 (2.2)].
`
`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 multiple myeloma 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 [see Warnings and Precautions (5.4)].
`
`
` 1
`
`
`INDICATIONS AND USAGE
`1.1
`Multiple Myeloma
`REVLIMID in combination with dexamethasone is indicated for the treatment of adult patients with multiple myeloma (MM).
`
`REVLIMID is indicated as maintenance therapy in adult patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT).
`1.2
`Myelodysplastic Syndromes
`REVLIMID is indicated for the treatment of adult 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.
`1.3
`Mantle Cell Lymphoma
`REVLIMID is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of
`which included bortezomib.
`1.4
`Follicular Lymphoma
`REVLIMID in combination with a rituximab product, is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL).
`1.5
`Marginal Zone Lymphoma
`REVLIMID in combination with a rituximab product, is indicated for the treatment of adult patients with previously treated marginal zone lymphoma (MZL).
`1.6
`Limitations of Use
`REVLIMID is not indicated and is not recommended for the treatment of patients with CLL outside of controlled clinical trials [see Warnings and Precautions (5.5)].
`
` 2
`
`
`DOSAGE AND ADMINISTRATION
`Recommended Dosage for Multiple Myeloma
`2.1
`REVLIMID Combination Therapy
`The recommended starting dose of REVLIMID is 25 mg orally once daily on Days 1-21 of repeated 28-day cycles in combination with dexamethasone. Refer to
`Section 14.1 for specific dexamethasone dosing. For patients greater than 75 years old, the starting dose of dexamethasone may be reduced [see Clinical Studies
`(14.1)]. Treatment should be continued until disease progression or unacceptable toxicity.
`
`In patients who are not eligible for auto-HSCT, treatment should continue until disease progression or unacceptable toxicity. For patients who are auto-HSCT-eligible,
`hematopoietic stem cell mobilization should occur within 4 cycles of a REVLIMID-containing therapy [see Warnings and Precautions (5.12)].
`Dose Adjustments for Hematologic Toxicities During MM Treatment
`Dose modification guidelines, as summarized in Table 1 below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4
`toxicity judged to be related to REVLIMID.
`
`Reference ID: 4987961
`
`3
`
`

`

`
`
`Table 1: Dose Adjustments for Hematologic Toxicities for MM
`Platelet counts
`Thrombocytopenia in MM
`
`
`When Platelets
`
`Fall below 30,000/mcL
`Return to at least 30,000/mcL
`
`For each subsequent drop below 30,000/mcL
`Return to at least 30,000/mcL
`
`Absolute Neutrophil counts (ANC)
`Neutropenia in MM
`When Neutrophils
`
`Fall below 1,000/mcL
`
`Return to at least 1,000/mcL and neutropenia is the only toxicity
`
`Return to at least 1,000/mcL and if other toxicity
`
`For each subsequent drop below 1,000/mcL
`Return to at least 1,000/mcL
`
`If at the 5 mg daily dose,
`For a subsequent drop below 30,000/mcL
`
`Return to at least 30,000/mcL
`
`Absolute Neutrophil counts (ANC)
`Neutropenia in MM
`When Neutrophils
`Fall below 500/mcL
`Return to at least 500/mcL
`
`If at 5 mg daily dose,
`For a subsequent drop below 500/mcL
`
`Return to at least 500/mcL
`
`Recommended Course
`Days 1-21 of repeated 28-day cycle
`Interrupt REVLIMID treatment, follow CBC weekly
`Resume REVLIMID at next lower dose. Do not dose
`below 2.5 mg daily
`Interrupt REVLIMID treatment
`Resume REVLIMID at next lower dose. Do not dose
`below 2.5 mg daily
`
`Recommended Course
`Days 1-21 of repeated 28-day cycle
`Interrupt REVLIMID treatment, follow CBC
`weekly
`Resume REVLIMID at 25 mg daily or initial
`starting dose
`Resume REVLIMID at next lower dose. Do not
`dose below 2.5 mg daily
`Interrupt REVLIMID treatment
`Resume REVLIMID at next lower dose. Do not
`dose below 2.5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment, follow CBC weekly
`Resume REVLIMID at next lower dose, continuously
`for Days 1-28 of repeated 28-day cycle
`Interrupt REVLIMID treatment. Do not dose below 5
`mg daily for Day 1 to 21 of 28 day cycle
`
`Resume REVLIMID at 5 mg daily for Days 1 to 21of
`28-day cycle. Do not dose below 5 mg daily for Day 1
`to 21 of 28 day cycle
`
`
`REVLIMID Maintenance Therapy Following Auto-HSCT
`Following auto-HSCT, initiate REVLIMID maintenance therapy after adequate hematologic recovery (ANC at least 1,000/mcL and/or platelet counts at least
`75,000/mcL). The recommended starting dose of REVLIMID is 10 mg once daily continuously (Days 1-28 of repeated 28-day cycles) until disease progression or
`unacceptable toxicity. After 3 cycles of maintenance therapy, the dose can be increased to 15 mg once daily if tolerated.
`
`Dose Adjustments for Hematologic Toxicities During MM Treatment
`Dose modification guidelines, as summarized in Table 2 below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4
`toxicity judged to be related to REVLIMID.
`Table 2: Dose Adjustments for Hematologic Toxicities for MM
`Platelet counts
`Thrombocytopenia in MM
`When Platelets
`Fall below 30,000/mcL
`Return to at least 30,000/mcL
`
`Recommended Course
`Interrupt REVLIMID treatment, follow CBC weekly
`Resume REVLIMID at next lower dose,
`continuously for Days 1-28 of repeated 28-day cycle
`Interrupt REVLIMID treatment. Do not dose below 5
`mg daily for Days 1 to 21 of 28-day cycle
`
`Resume REVLIMID at 5 mg daily for Days 1 to 21 of
`28-day cycle. Do not dose below 5 mg daily for Days
`1 to 21 of 28-day cycle
`
`
`Recommended Dosage for Myelodysplastic Syndromes
`2.2
`The recommended starting dose of REVLIMID is 10 mg daily. Treatment is continued or modified based upon clinical and laboratory findings. Continue treatment
`until disease progression or unacceptable toxicity.
`Dose Adjustments for Hematologic Toxicities During MDS Treatment
`Patients who are dosed initially at 10 mg and who experience thrombocytopenia should have their dosage adjusted as follows:
`
`Reference ID: 4987961
`
`4
`
`

`

`Platelet counts
`If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS
`
`
`
`
`Recommended Course
`Interrupt REVLIMID treatment
`Resume REVLIMID at 5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment
`Resume REVLIMID at 5 mg daily
`
`Resume REVLIMID at 5 mg daily
`
`Resume REVLIMID at 5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment
`
`Resume REVLIMID at 2.5 mg daily
`
`If baseline is at least 100,000/mcL
`When Platelets
`Fall below 50,000/mcL
`Return to at least 50,000/mcL
`If baseline is below 100,000/mcL
`When Platelets
`Fall to 50% of the baseline value
`If baseline is at least 60,000/mcL and
`returns to at least 50,000/mcL
`If baseline is below 60,000/mcL and
`returns to at least 30,000/mcL
`
` If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS
`When Platelets
`Recommended Course
`Fall below 30,000/mcL or below 50,000/mcL
`Interrupt REVLIMID treatment
`with platelet transfusions
`Return to at least 30,000/mcL
`(without hemostatic failure)
`Patients who experience thrombocytopenia at 5 mg daily should have their dosage adjusted as follows:
`If thrombocytopenia develops during treatment at 5 mg daily in MDS
`When Platelets
`Fall below 30,000/mcL or below 50,000/mcL
`with platelet transfusions
`Return to at least 30,000/mcL
`(without hemostatic failure)
`
`Patients who are dosed initially at 10 mg and experience neutropenia should have their dosage adjusted as follows:
`Absolute Neutrophil counts (ANC)
`If neutropenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS
`
`
`If baseline ANC is at least 1,000/mcL
`When Neutrophils
`Fall below 750/mcL
`Return to at least 1,000/mcL
`If baseline ANC is below 1,000/mcL
`When Neutrophils
`Fall below 500/mcL
`Return to at least 500/mcL
`
`Recommended Course
`Interrupt REVLIMID treatment
`Resume REVLIMID at 5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment
`Resume REVLIMID at 5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment
`
`
`If neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS
`
`
`When Neutrophils
`Fall below 500/mcL for at least 7 days or below 500/mcL
`associated with fever (at least 38.5°C)
`Resume REVLIMID at 5 mg daily
`Return to at least 500/mcL
`Patients who experience neutropenia at 5 mg daily should have their dosage adjusted as follows:
`If neutropenia develops during treatment at 5 mg daily in MDS
`
`
`When Neutrophils
`Fall below 500/mcL for at least 7 days or below 500/mcL
`associated with fever (at least 38.5°C)
`Return to at least 500/mcL
`
`Recommended Course
`Interrupt REVLIMID treatment
`
`Resume REVLIMID at 2.5 mg daily
`
`
`
`
`
`
`
`Reference ID: 4987961
`
`5
`
`

`

`
`Recommended Dosage for Mantle Cell Lymphoma
`2.3
`The recommended starting dose of REVLIMID is 25 mg/day orally on Days 1-21 of repeated 28-day cycles for relapsed or refractory mantle cell lymphoma.
`Treatment should be continued until disease progression or unacceptable toxicity.
`
`Treatment is continued, modified or discontinued based upon clinical and laboratory findings.
`Dose Adjustments for Hematologic Toxicities During MCL Treatment
`Dose modification guidelines as summarized below are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicities
`considered to be related to REVLIMID.
`Platelet counts
`Thrombocytopenia during treatment in MCL
`
`
`
`
`Recommended Course
`Interrupt REVLIMID treatment and follow CBC weekly
`
`Resume REVLIMID at 5 mg less than the previous dose. Do
`not dose below 5 mg daily
`
`
`Recommended Course
`Interrupt REVLIMID treatment and follow CBC weekly
`
`When Platelets
`Fall below 50,000/mcL
`
`Return to at least 50,000/mcL
`
`
`Absolute Neutrophil counts (ANC)
`Neutropenia during treatment in MCL
`When Neutrophils
`Fall below 1,000/mcL for at least 7 days
`OR
`Falls below 1,000/mcL with an associated temperature at least
`38.5°C
`OR
`Falls below 500/mcL
`
`Return to at least 1,000/mcL
`
`
`Recommended Dosage for Follicular Lymphoma or Marginal Zone Lymphoma
`2.4
`The recommended starting dose of REVLIMID is 20 mg orally once daily on Days 1-21 of repeated 28-day cycles for up to 12 cycles of treatment in combination with
`a rituximab-product. Refer to Section 14.4 for specific rituximab dosing from the AUGMENT trial. For dose adjustments due to toxicity with rituximab, refer to the
`product prescribing information.
`
`Dose Adjustments for Hematologic Toxicities during FL or MZL Treatment
`
`Dose modification guidelines, as summarized below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged
`to be related to REVLIMID.
`Platelet counts
`Thrombocytopenia during treatment in FL or MZL
`When Platelets
`Fall below 50,000/mcL
`
`Return to at least 50,000/mcL
`
`
`Resume REVLIMID at 5 mg less than the previous dose. Do
`not dose below 5 mg daily
`
`Recommended Course
`Interrupt REVLIMID treatment and follow CBC weekly.
`
`If patient starting dose was 20 mg daily, resume REVLIMID
`at 5 mg less than the previous dose. Do not dose below 5 mg
`daily.
`
`If patient starting dose was 10 mg daily, resume at 5 mg less
`than previous dose. Do not dose below 2.5 mg daily.
`
`
`Recommended Course
`Interrupt REVLIMID treatment and follow CBC weekly.
`
`
`If patient starting dose was 20 mg daily, resume REVLIMID
`at 5 mg less than the previous dose. Do not dose below 5 mg
`daily.
`
`
`
`
`
`Absolute Neutrophil counts (ANC)
`Neutropenia during treatment in FL or MZL
`When Neutrophils
`Fall below 1,000/mcL for at least 7 days
`OR
`Falls below 1,000/mcL with an associated temperature at least
`38.5°C
`OR
`Falls below 500 /mcL
`
`Return to at least 1,000/mcL
`
`Reference ID: 4987961
`
`6
`
`

`

`
`If patient starting dose was 10 mg daily, resume at 5 mg less
`than previous dose. Do not dose below 2.5 mg daily.
`
`
`Dosage Modifications for Non-Hematologic Adverse Reactions
`2.5
`For non-hematologic Grade 3/4 toxicities judged to be related to REVLIMID, hold treatment and restart at the physician's discretion at next lower dose level when
`toxicity has resolved to Grade 2 or below.
`Permanently discontinue REVLIMID for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reactions [see Warnings and
`Precautions (5.9, 5.15)].
`2.6
`Recommended Dosage for Patients with Renal Impairment
`The recommendations for dosing patients with renal impairment are shown in the following table [see Clinical Pharmacology (12.3)].
`
`
`Renal Function
`(Cockcroft-Gault)
`
`CLcr 30 to 60 mL/min
`CLcr below 30 mL/min (not requiring
`dialysis)
`CLcr below 30 mL/min (requiring
`dialysis)
`
`Table 3: Dose Adjustments for Patients with Renal Impairment
`Dose in REVLIMID Combination
`Dose in REVLIMID Combination
`Therapy for MM and MCL
`Therapy for FL and MZL
`
`10 mg once daily
`15 mg every other day
`
`5 mg once daily. On dialysis days,
`administer the dose following
`dialysis.
`
`10 mg once daily
`5 mg once daily
`
`5 mg once daily. On dialysis days,
`administer the dose following
`dialysis.
`
`Dose in REVLIMID Maintenance
`Therapy Following Auto-HSCT for
`MM and for MDS
`5 mg once daily
`2.5 mg once daily
`
`2.5 mg once daily. On dialysis days,
`administer the dose following
`dialysis.
`
`
`REVLIMID Combination Therapy for MM: For CLcr of 30 to 60 mL/min, consider escalating the dose to 15 mg after 2 cycles if the patient tolerates the 10 mg dose of
`lenalidomide without dose-limiting toxicity.
`
`REVLIMID Maintenance Therapy Following Auto-HSCT for MM and for MCL and MDS: Base subsequent REVLIMID dose increase or decrease on individual
`patient treatment tolerance [see Dosage and Administration (2.1- 2.3)].
`
`REVLIMID Combination Therapy for FL or for MZL: For patients with CLcr of 30 to 60 mL/min, after 2 cycles, the REVLIMID dose may be increased to 15 mg
`orally if the patient has tolerated therapy.
`2.7
`Administration
`Advise patients to take REVLIMID orally at about the same time each day, either with or without food. Advise patients to swallow REVLIMID capsules whole with
`water and not to open, break, or chew them.
`
`
`
`
`DOSAGE FORMS AND STRENGTHS
`
` 3
`
`
`Capsules:
`
`
`
`
`
`
`
`
`
`2.5 mg, white and blue-green opaque hard capsules imprinted “REV” on one half and “2.5 mg” on the other half in black ink
`5 mg, white opaque capsules imprinted “REV” on one half and “5 mg” on the other half in black ink
`10 mg, blue/green and pale yellow opaque capsules imprinted “REV” on one half and “10 mg” on the other half in black ink
`15 mg, powder blue and white opaque capsules imprinted “REV” on one half and “15 mg” on the other half in black ink
`20 mg, powder blue and blue-green opaque hard capsules imprinted “REV” on one half and “20 mg” on the other half in black ink
`25 mg, white opaque capsules imprinted “REV” on one half and “25 mg” on the other half in black ink
`
`
`
` 4
`
`
`CONTRAINDICATIONS
`4.1
`Pregnancy
`REVLIMID can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with
`lenalidomide during organogenesis. This effect was seen at all doses tested. Due to the results of this developmental monkey study, and lenalidomide’s structural
`similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in females who are pregnant [see Boxed Warning]. 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 a fetus [see Warnings and Precautions (5.1,
`5.2), Use in Special Populations (8.1, 8.3)].
`4.2
`Severe Hypersensitivity Reactions
`REVLIMID is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to
`lenalidomide [see Warnings and Precautions (5.9, 5.15)].
`
` 5
`
`
`WARNINGS AND PRECAUTIONS
`5.1
`Embryo-Fetal Toxicity
`REVLIMID 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.
`
`Reference ID: 4987961
`
`7
`
`

`

`
`
`
`REVLIMID is 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 REVLIMID 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 REVLIMID, during therapy, during dose interruptions and continuing for 4 weeks following discontinuation of REVLIMID 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 REVLIMID 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 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 and for up to 4 weeks after discontinuing REVLIMID [see Use in Specific Populations (8.3)].
`
`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.
`5.2
`Lenalidomide REMS Program
`Because of the embryo-fetal risk [see Warnings and Precautions (5.1)], REVLIMID is 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 REVLIMID and comply with
`REMS requirements.
`
`
`Further information about the Lenalidomide REMS program is available at www.lenalidomiderems.com or by telephone at 1-888-423-5436.
`
`Reference ID: 4987961
`
`8
`
`

`

`
`
`5.3
`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 medication that may increase risk of bleeding. Patients taking REVLIMID 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 REVLIMID in combination with dexamethasone or as REVLIMID 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