FULL PRESCRIBING INFORMATION

1INDICATIONS AND USAGE

1.1Multiple Myeloma

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

1.2Myelodysplastic Syndromes

REVLIMID 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.

2DOSAGE AND ADMINISTRATION

2.1 Multiple Myeloma

The recommended starting dose of REVLIMID is 25 mg once daily orally with water on Days 1-21 of repeated 28-day cycles. Patients should not break, chew or open the capsules. The recommended dose of dexamethasone is 40 mg once daily on Days 1-4, 9-12, and 17-20 of each 28-day cycle for the first 4 cycles of therapy and then 40 mg once daily orally on Days 1-4 every 28 days. Treatment is continued or modified based upon clinical and laboratory findings.

Dose Adjustments for Hematologic Toxicities During Multiple Myeloma 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 lenalidomide.

Platelet counts

Thrombocytopenia in MM

Absolute Neutrophil counts (ANC)

Neutropenia in MM

Other Grade 3 / 4 Toxicities in MM

For other Grade 3/4 toxicities judged to be related to REVLIMID, hold treatment and restart at next lower dose level when toxicity has resolved to ≤ Grade 2.

Starting Dose Adjustment for Renal Impairment in MM

Since REVLIMD 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 and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to nonmalignant conditions, REVLIMID starting dose adjustment is recommended for patients with CLcr < 60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 7 mL/min have not been studied. The recommendations for initial starting doses for patients with multiple myeloma (MM) are as follows:

After initiation of REVLIMID therapy, subsequent REVLIMID dose modification should be based on individual patient treatment tolerance, as described elsewhere in this section.

2.2Myelodysplastic Syndromes

The recommended starting dose of REVLIMID is 10 mg daily with water. Patients should not break, chew or open the capsules. Treatment is continued or modified based upon clinical and laboratory findings.

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:

Platelet counts

If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS

If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS

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

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 neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS

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

Starting Dose Adjustment for Renal Impairment in MDS:
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 and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to nonmalignant conditions, REVLIMID starting dose adjustment is recommended for patients with CLcr < 60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 7 mL/min have not been studied. The recommendations for initial starting doses for patients with myelodysplastic syndromes (MDS) are as follows:

After initiation of REVLIMID therapy, subsequent REVLIMID dose modification should be based on individual patient treatment tolerance, as described elsewhere in this section.

3DOSAGE FORMS AND STRENGTHS

REVLIMID 5 mg, 10 mg, 15 mg and 25 mg capsules will be supplied through the RevAssist program

REVLIMID is available in the following capsule strengths:

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
25 mg: White opaque capsules imprinted “REV” on one half and “25 mg” on the other half in black ink

4CONTRAINDICATIONS

4.1Pregnancy

REVLIMID may cause fetal harm when administered to a pregnant woman. 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 pregnant women and women capable of becoming pregnant [see Boxed Warning]. Females of childbearing potential may be treated with lenalidomide provided adequate precautions are taken to avoid pregnancy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods of reliable birth control, including at least one highly effective method (e.g., hormonal contraception, tubal ligation, IUD or partner’s vasectomy) and one additional effective method (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to initiating treatment with REVLIMID, during therapy, during therapy delay, and continuing for 4 weeks following discontinuation of REVLIMID therapy. If hormonal or IUD contraception is medically contraindicated, two other effective or highly effective methods may be used.

Females of childbearing potential being treated with REVLIMID must have pregnancy testing (sensitivity of at least 50 mIU/mL). The first test should be performed within 10-14 days and the second test within 24 hours prior to beginning REVLIMID therapy and then weekly during the first month, then monthly thereafter in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles. Pregnancy testing and counseling must be performed if a patient misses her period or if there is any abnormality in menstrual bleeding. If pregnancy occurs, REVLIMID must be immediately discontinued. Under these conditions, the patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further eva luation and counseling.

4.2Allergic Reactions

REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide [see Warnings and precautions (5.5)}.

5WARNINGS AND PRECAUTIONS

5.1Fetal Risk

REVLIMID is a thalidomide analogue. Thalidomide is 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.

There are no adequate and well-controlled studies in pregnant females.

5.2 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.

Please see the following information for prescribers, female patients, and male patients about this restricted distribution program.

RevAssist Program Description

Prescribers

REVLIMID can be prescribed only by licensed prescribers who are registered in the RevAssist program and understand the potential risk of teratogenicity if lenalidomide is used during pregnancy.

Effective contraception must be used by female patients of childbearing potential for at least 4 weeks before beginning REVLIMID therapy, during therapy, during dose interruptions and for 4 weeks following discontinuation of REVLIMID therapy. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or because the patient has been postmenopausal naturally for at least 24 consecutive months. Females of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed. Sexually mature females who have not undergone a hysterectomy, have not had a bilateral oophorectomy or who have not been postmenopausal naturally for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months) are considered to be females of childbearing potential. Two reliable forms of contraception must be used simultaneously unless continuous abstinence from heterosexual sexual contact is the chosen method.

Females of childbearing potential must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL). The first test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing REVLIMID. A prescription for REVLIMID for a female of childbearing potential must not be issued by the prescriber until negative pregnancy tests have been verified by the prescriber.

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.

Once treatment has started and during dose interruptions, pregnancy testing for females of childbearing potential should occur weekly during the first 4 weeks of use, then pregnancy testing should be repeated every 4 weeks in females with regular menstrual cycles. If menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her pregnancy test or in her menstrual bleeding. REVLIMID treatment must be discontinued during this eva luation.

Pregnancy test results should be verified by the prescriber and the pharmacist prior to dispensing any prescription.

If pregnancy does occur during treatment, REVLIMID must be discontinued immediately.

Any suspected fetal exposure to REVLIMID must be reported to the FDA via the MedWatch number at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436. The patient should be referred to an obstetrician/gynecologist experienced in reproductive toxicity for further eva luation and counseling.

Female Patients

REVLIMID may be used in females of childbearing potential only when the PATIENT MEETS ALL OF THE FOLLOWING CONDITIONS (i.e., she is unable to become pregnant while on REVLIMID therapy):

• she is capable of complying with the mandatory contraceptive measures, pregnancy testing, patient registration, and patient survey as described in the RevAssist program.
• she has received and understands both oral and written warnings of the potential risks of taking REVLIMID during pregnancy and of exposing a fetus to the drug.
• she has received both oral and written warnings of the risk of possible contraception failure and of the need to use two reliable forms of contraception simultaneously (one highly effective form of contraception – tubal ligation, IUD, hormonal (birth control pills, injections, patch or implants) or partner’s vasectomy and one additional effective contraceptive method - latex condom, diaphragm or cervical cap, unless continuous abstinence from heterosexual sexual contact is the chosen method. Sexually mature females who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months (i.e., who have had menses at some time in the preceding 24 consecutive months), or had a bilateral oophorectomy are considered to be females of childbearing potential.
• she acknowledges, in writing, her understanding of these warnings and of the need for using two reliable methods of contraception for 4 weeks prior to beginning REVLIMID therapy, during therapy, during dose interruptions and for 4 weeks after discontinuation of therapy.
• she has had two negative pregnancy tests with a sensitivity of at least 50 mIU/mL, within 10-14 days and 24 hours prior to beginning therapy.
• if the patient is between 12 and 18 years of age, her parent or legal guardian must have read the educational materials and agreed to ensure compliance with the above.

Male Patients

REVLIMID may be used in sexually active males when the PATIENT MEETS ALL OF THE FOLLOWING CONDITIONS: