Revlimid Lenalidomide 5 mg Capsule, 28-count — NDC 59572-405-28 (Billing 59572-0405-28)

1 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 ).

1.1Multiple 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).

1.2Myelodysplastic 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.

1.3Mantle 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.

1.4Follicular Lymphoma REVLIMID in combination with a rituximab product, is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL).

1.5Marginal Zone Lymphoma REVLIMID in combination with a rituximab product, is indicated for the treatment of adult patients with previously treated marginal zone lymphoma (MZL).

1.6Limitations 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 • 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 ).

2.1Recommended Dosage for Multiple Myeloma 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. Table 1: Dose Adjustments for Hematologic Toxicities for MM Platelet counts Thrombocytopenia in MM When Platelets Recommended Course Days 1-21 of repeated 28-day cycle Fall below 30,000/mcL Interrupt REVLIMID treatment, follow CBC weekly Return to at least 30,000/mcL Resume REVLIMID at next lower dose.

Do not dose below 2.5 mg daily For each subsequent drop below 30,000/mcL Interrupt REVLIMID treatment Return to at least 30,000/mcL Resume REVLIMID at next lower dose. Do not dose below 2.5 mg daily Absolute Neutrophil counts (ANC) Neutropenia in MM When Neutrophils Recommended Course Days 1-21 of repeated 28-day cycle Fall below 1,000/mcL Interrupt REVLIMID treatment, follow CBC weekly Return to at least 1,000/mcL and neutropenia is the only toxicity Resume REVLIMID at 25 mg daily or initial starting dose Return to at least 1,000/mcL and if other toxicity Resume REVLIMID at next lower dose.

Do not dose below 2.5 mg daily For each subsequent drop below 1,000/mcL Interrupt REVLIMID treatment Return to at least 1,000/mcL Resume REVLIMID at next lower dose. Do not dose below 2.5 mg daily 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 Recommended Course Fall below 30,000/mcL Interrupt REVLIMID treatment, follow CBC weekly Return to at least 30,000/mcL Resume REVLIMID at next lower dose, continuously for Days 1-28 of repeated 28-day cycle If at the 5 mg daily dose, For a subsequent drop below 30,000/mcL Interrupt REVLIMID treatment.

Do not dose below 5 mg daily for Day 1 to 21… [Excerpted — this section continues on DailyMed.]

3 DOSAGE FORMS AND STRENGTHS 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 Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg ( 3 ).

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved Patient labeling (Medication Guide) Embryo-Fetal Toxicity Advise patients that REVLIMID is contraindicated in pregnancy [see Boxed Warning and Contraindications (4.1) ]. REVLIMID is a thalidomide analogue and can cause serious birth defects or death to a developing baby [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . • Advise females of reproductive potential that they must avoid pregnancy while taking REVLIMID and for at least 4 weeks after completing therapy. • Initiate REVLIMID treatment in females of reproductive potential only following a negative pregnancy test. • Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception including at least 1 highly effective form, simultaneously during REVLIMID therapy, during dose interruption and for 4 weeks after she has completely finished taking REVLIMID.

Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch or implants) and a partner's vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm and cervical cap. • Instruct patient to immediately stop taking REVLIMID and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period, or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant. • Advise patient that if her healthcare provider is not available, she should call the REMS Call Center at 1-888-423-5436 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ]. • Advise males to 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. • Advise male patients taking REVLIMID that they must not donate sperm and for up to 4 weeks after discontinuation of REVLIMID [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] . • All patients must be instructed to not donate blood while taking REVLIMID, during dose interruptions and for 4 weeks following discontinuation of REVLIMID [see Warnings and Precautions (5.1) ] .

Lenalidomide REMS program Because of the risk of embryo-fetal toxicity, REVLIMID is only available through a restricted program called the Lenalidomide REMS program [see Warnings and Precautions (5.2) ] . • Patients must sign a Patient-Physician agreement form and comply with the requirements to receive REVLIMID. In particular, females of reproductive potential must comply with the pregnancy testing, contraception requirements and participate in monthly telephone surveys. Males must comply with the contraception requirements [see Use in Specific Populations (8.3) ] . • REVLIMID is available only from pharmacies that are certified in the Lenalidomide REMS program.

Provide patients with the telephone number and website for information on how to obtain the product. Pregnancy Exposure Registry Inform females there is a Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436 [see Use in Specific Populations (8.1) ] . Hematologic Toxicity Inform patients that REVLIMID is associated with significant neutropenia and thrombocytopenia [see Boxed Warning and Warnings and Precautions (5.3) ] .

Venous and Arterial Thromboembolism Inform patients of the risk of thrombosis including DVT, PE, MI, and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation [see Boxed Warning and Warnings and Precautions (5.4) ] . Increased Mortality in Patients with CLL Inform patients that RE… [Excerpted — this section continues on DailyMed.]

Medication Guide REVLIMID ® (rev-li-mid) (lenalidomide) capsules What is the most important information I should know about REVLIMID? Before you begin taking REVLIMID, you must read and agree to all of the instructions in the Lenalidomide REMS program. For more information, call 1-888-423-5436 or go to www.lenalidomiderems.com.

Before prescribing REVLIMID, your healthcare provider will explain the Lenalidomide REMS program to you and have you sign the Patient-Physician Agreement Form. REVLIMID may cause serious side effects including: • Possible birth defects (deformed babies) or death of an unborn baby . Females who are pregnant or who plan to become pregnant must not take REVLIMID.

REVLIMID is similar to the medicine thalidomide. We know thalidomide can cause severe life-threatening birth defects. REVLIMID has not been tested in pregnant females.

REVLIMID has harmed unborn animals in animal testing. Females must not get pregnant: o For at least 4 weeks before starting REVLIMID o While taking REVLIMID o During any breaks (interruptions) in your treatment with REVLIMID o For at least 4 weeks after stopping REVLIMID Females who can become pregnant: o Will have pregnancy tests weekly for 4 weeks, then every 4 weeks if your menstrual cycle is regular, or every 2 weeks if your menstrual cycle is irregular. o If you miss your period or have unusual bleeding, you will need to have a pregnancy test and receive counseling. o Must agree to use two acceptable forms of birth control at the same time, for at least 4 weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least 4 weeks after stopping REVLIMID. o Talk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with REVLIMID. o If you had unprotected sex or if you think your birth control has failed, stop taking REVLIMID immediately and call your healthcare provider right away.

If you become pregnant while taking REVLIMID, stop taking it right away and call your healthcare provider. If your healthcare provider is not available, you can call the REMS Call Center at 1-888-423-5436. Healthcare providers and patients should report all cases of pregnancy to: o FDA MedWatch at 1-800-FDA-1088, and o REMS Call Center at 1-888-423-5436 There is a pregnancy exposure registry that monitors the outcomes of females who take REVLIMID during pregnancy, or if their male partner takes REVLIMID and they are exposed during pregnancy.

You can enroll in this registry by calling the REMS Call Center at the phone number listed above. REVLIMID can pass into human semen: o Males, including those who have had a vasectomy, must always use a latex or synthetic condom during any sexual contact with a pregnant female or a female that can become pregnant while taking REVLIMID, during any breaks (interruptions) in your treatment with REVLIMID, and for up to 4 weeks after stopping REVLIMID. o Do not have unprotected sexual contact with a female who is or could become pregnant.

Tell your healthcare provider if you do have unprotected sexual contact with a female who is or could become pregnant. o Do not donate sperm while taking REVLIMID, during any breaks (interruptions) in your treatment, and for up to 4 weeks after stopping REVLIMID. If a female becomes pregnant with your sperm, the baby may be exposed to REVLIMID and may be born with birth defects. Men, if your female partner becomes pregnant, you should call your healthcare provider right away. • Low white blood cells (neutropenia) and low platelets (thrombocytopenia).

REVLIMID causes low white blood cells and low platelets in most people. You may need a blood transfusion or certain medicines if your blood counts drop too low. Your healthcare provider should check your blood counts often especially during the first several months of treatment with REVLIMID, and then at least monthly.

Tell your healthcare provide… [Excerpted — this section continues on DailyMed.]