Digoxin: Periodic monitoring of digoxin plasma levels is recommended 

due to increased Cmax and AUC with concomitant REVLIMID therapy 

.

Patients taking concomitant therapies such as erythropoietin stimulating 

agents or estrogen containing therapies may have an increased risk of 

venous thromboembolism (VTE) .

 

 

 

MM: Most common adverse reactions (.20%) include fatigue, neutropenia, 

constipation, diarrhea, muscle cramp, anemia, pyrexia, peripheral edema, 

nausea, back pain, upper respiratory tract infection, dyspnea, dizziness,

 thrombocytopenia, tremor and rash 

.

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 .

.

MCL: Most common adverse reactions (.15%) include neutropenia, 

thrombocytopenia, fatigue, diarrhea, anemia, nausea, cough, pyrexia, rash, 

dyspnea, pruritus, constipation, peripheral edema and leukopenia 

CONTRAINDICATIONS

Pregnancy (Boxed Warnings, 

.

Demonstrated hypersensitivity to lenalidomide .

 

 WARNINGS AND PRECAUTIONS.

 

Increased mortality: serious and fatal cardiac adverse reactions were observed

 in patients with CLL .

.

Second Primary Malignancies (SPM): Higher incidences of SPM were observed

 in controlled trials of patients with multiple myeloma receiving REVLIMID .

.

Hepatotoxicity: Hepatic failure including fatalities; monitor liver function. 

Stop REVLIMID and evaluate if hepatotoxicity is suspected 

.

Allergic Reactions, including fatalities: Hypersensitivity, angioedema, 

Stevens-Johnson syndrome, toxic epidermal necrolysis; discontinue 

REVLIMID if reactions are suspected. Do not resume REVLIMID if these

 reactions are verified 

.

Tumor lysis syndrome (TLS) including fatalities: Monitor patients at

 risk of TLS  (i.e., those with high tumor burden) and take appropriate

 precautions .

.

Tumor flare reaction: Serious tumor flare reactions have occurred during 

investigational use of REVLIMID for chronic lymphocytic leukemia 

and lymphoma 

 

INDICATIONS AND USAGE

 

 REVLIMID is a thalidomide analogue indicated for the treatment of patients with:

Multiple myeloma (MM), in combination with dexamethasone, in patients 

who have received at least one prior therapy 

 

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 

 

Mantle cell lymphoma (MCL) whose disease has relapsed or progressed 

after two prior therapies, one of which included bortezomib 

 

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 

 

 DOSAGE AND ADMINISTRATION

 

MM: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles. 

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/day orally on Days 1-4 every 28 days 

 

MDS: 10 mg once daily .

MCL: 25 mg once daily orally on Days 1-21 of repeated 28-day cycles 

Continue or modify dosing based on clinical and laboratory findings 

 

Renal impairment: Adjust starting dose in patients with moderate or severe 

renal impairment and on dialysis (CLcr<60 mL/min) 

 

 DOSAGE FORMS AND STRENGTHS

Capsules: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg 

 PATIENT COUNSELING INFORMATION

 

See FDA-approved Patient labeling (Medication Guide)

 

1.Embryo-Fetal Toxicity Advise patients that REVLIMID is contraindicated in 

pregnancy 

 

2. REVLIMID is a thalidomide analog and can cause serious birth defects or deat

 to a developing baby. .

 

3.Advise females of reproductive potential that they must avoid pregnancy while taking 

REVLIMID and for at least 4 weeks after completing therapy.

 

4.Initiate REVLIMID treatment in females of reproductive potential only following a

 negative pregnancy test.

 

5.Advise females of reproductive potential of the importance of monthly pregnancy tests

 and the need to use two different forms of contraception including at least one

 highly effective form simultaneously during REVLIMID therapy, during dose 

 interruption and for 4 weeks after she has completely finished taking REVLIMID.

 

6. 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.

 

7. Additional effective contraceptive methods include latex or synthetic condom,

  diaphragm and cervical cap.

 

8.Instruct patient to immediately stop taking REVLIMID and contact her doctor 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.

 

9.Advise patient that if her doctor is not available, she can call 1-888-668-2528

  for information on emergency contraception .

 

10.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 28 days after discontinuing REVLIMID, even if they have undergone 

  a successful vasectomy.

 

11.Advise male patients taking REVLIMID that they must not donate sperm .

 

12.All patients must be instructed to not donate blood while taking REVLIMID,

  during dose interruptions and for 1 month following discontinuation of REVLIMID 

 

13.REVLIMID REMS program- Because of the risk of embryo-fetal toxicity, REVLIMID

  is only available through a restricted program called the REVLIMID REMS

  program (formerly known as the RevAssist® program) .

 

 14.Patients must sign a Patient-Prescriber 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 

 

15.REVLIMID is available only from pharmacies that are certified in REVLIMID

  REMS program. Provide patients with the telephone number and website for

  information on how to obtain the product.

 

16.Hematologic Toxicity

 Inform patients that REVLIMID is associated with significant neutropenia and 

 thrombocytopenia 

 

17.Venous Thromboembolism

Inform patients that REVLIMID/dexamethasone has demonstrated significant increased 

 risk of DVT and PE in patients with multiple myeloma .

 

18.Increased Mortality in Patients with CLL

 Inform patients that REVLIMID had increased mortality in patients with CLL and serious 

 adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction,

  and cardiac failure 

 

19.Second Primary Malignancies

 Inform patients of the potential risk of developing second primary malignancies during 

 treatment with REVLIMID.

 

20.Hepatotoxicity

  Inform patients of the risk of hepatotoxicity, including hepatic failure and death, and

 to report any signs and symptoms associated with this event to their healthcare 

 provider for evaluation.

 

21.Allergic Reactions

 Inform patients of the potential for allergic reactions including hypersensitivity, 

  angioedema, Stevens Johnsons Syndrome, or toxic epidermal necrolysis if they

  had such a reaction to THALOMID and report symptoms associated with these

  events to their healthcare provider for evaluation.

 

22.Tumor Lysis Syndrome

 Inform patients of the potential risk of tumor lysis syndrome and to report any signs 

 and symptoms associated with this event to their healthcare provider for evaluation.

 

23.Tumor Flare Reaction

 Inform patients of the potential risk of tumor flare reaction and to report any signs and

 symptoms associated with this event to their healthcare provider for evaluation.

 

24.Dosing Instructions

 Inform patients to take REVLIMID once daily at about the same time each day, 

 either with or without food. The capsules should not be opened, broken, or chewed.

 REVLIMID should be swallowed whole with water.

 

25.Instruct patients that if they miss a dose of REVLIMID, they may still take it up to

  12 hours after the time they would normally take it. If more than 12 hours have

  elapsed, they should be instructed to skip the dose for that day. 

  The next day, they should take REVLIMID at the usual time. Warn patients to not

   take 2 doses to make up for the one that they missed.

 

Manufactured for: Celgene Corporation Summit, NJ 07901

 

 

 USE IN SPECIFIC POPULATIONS

 

1.Pregnancy

 Pregnancy Category X 

 Risk Summary

 REVLIMID can cause embryo-fetal harm when administered to a pregnant female and

 is contraindicated during pregnancy. REVLIMID is a thalidomide analogue.

 

Thalidomide is a human teratogen, inducing a high frequency of severe and 

life-threatening birth defects such as amelia (absence of limbs), phocomelia 

(short limbs), hypoplasticity of the bones, absence of bones, external ear 

abnormalities (including anotia, micropinna, small or absent external auditory canals),

 facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital 

heart defects. Alimentary tract, urinary tract, and genital malformations 

have also been documented and mortality at or shortly after birth has been 

reported in about 40% of infants.

 

2. Nursing mothers

 It is not known whether this drug is excreted in human milk. Because many drugs are

 excreted in human milk and because of the potential for adverse reactions in nursing

 infants from lenalidomide, a decision should be made whether to discontinue 

 nursing or to discontinue the drug, taking into account the importance of the drug

 to the mother.

 

3. Pediatric use

 Safety and effectiveness in pediatric patients below the age of 18 have not been established.

 

8.5 Geriatric use

REVLIMID has been used in multiple myeloma (MM) clinical trials in patients up to

 86 years of age.

Of the 703 MM patients who received study treatment in Studies 1 and 2, 45% were age 65 or over while 12% of patients were age 75 and over. The percentage of patients age 65 or over was not significantly different between the REVLIMID/dexamethasone and placebo/dexamethasone groups. Of the 353 patients who received REVLIMID/dexamethasone, 46% were age 65 and over. In both studies, patients > 65 years of age were more likely than patients . 65 years of age to experience DVT, pulmonary embolism, atrial fibrillation, and renal failure following use of REVLIMID. No differences in efficacy were observed between patients over 65 years of age and younger patients

.