Lenalidomide
Dosing & Indications
· Adult Dose
· Revlimid(R) is only available under a restricted distribution program called
RevAssist(SM). Details are available at www. revlimid.com or at 888-423-5436
· Multiple myeloma, In combination with dexamethasone, first-line therapy: (high-
dose dexamethasone) 25 mg ORALLY daily on days 1 to 21 of a 28-day cycle; co-
administer dexamethasone 40 mg ORALLY daily on days 1 to 4, 9 to 12, and 17 to 20 of
each 28-day cycle
· Multiple myeloma, In combination with dexamethasone, first-line therapy: (low-dose
dexamethasone) 25 mg ORALLY daily on days 1 to 21 of a 28-day cycle; co-administer
dexamethasone 40 mg ORALLY on days 1, 8, 15, and 22 of each 28-day cycle
· Multiple myeloma, in combination with dexamethasone, in patients who have
received at least 1 prior therapy: initial, 25 mg ORALLY daily with water (as a single 25
mg capsule) on days 1 to 21 of a 28-day cycle; co-administer dexamethasone 40 mg/day
ORALLY on days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles,
then 40 mg/day ORALLY on days 1 to 4 every 28 days; continue therapy, with dose
adjustments for toxicities, until disease progression
· Myelodysplastic syndrome, Transfusion-dependent, deletion 5q abnormality, low or
intermediate-1 risk: 10 mg ORALLY once daily with water
· Pediatric Dose
· safety and effectiveness not established in children
· Dose Adjustments
· (multiple myeloma): if absolute neutrophil count (ANC) is < 1,000/mcL, stop
lenalidomide, add granulocyte colony-stimulating factor and resume at 25 mg daily when
ANC returns to 1,000/mcL or more and neutropenia is the only toxicity; if ANC returns
to 1,000/mcL or more and other toxicity is present, resume at 15 mg daily; for each
subsequent ANC drop to < 1,000/mcL, stop lenalidomide and resume at 5 mg less than
previous dose when ANC returns to 1,000/mcL or more; do not dose below 5 mg daily
· (multiple myeloma): if platelet count is < 30,000/mcL, stop lenalidomide and resume
at reduced dose of 15 mg daily when platelet count is 30,000/mcL or more; for each
subsequent drop to < 30,000/mcL, stop lenalidomide and resume at 5 mg less than
previous dose when platelet count is 30,000/mcL or more; do not dose below 5 mg daily
· (multiple myeloma) other grade 3/4 toxicities: stop lenalidomide and restart at the
next lower dose level when the toxicity is at or below grade 2
· (myelodysplastic syndrome) neutropenia WITHIN 4 weeks of starting 10 mg daily,
baseline absolute neutrophil count (ANC) >= 1000/mcL: stop lenalidomide for ANC <
750/mcL; resume at reduced dose of 5 mg ORALLY once daily when ANC returns to >=
1000/mcL

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· (myelodysplastic syndrome) neutropenia WITHIN 4 weeks of starting 10 mg daily,
baseline absolute neutrophil count (ANC) < 1000/mcL: stop lenalidomide for ANC <
500/mcL; resume at reduced dose of 5 mg ORALLY once daily when ANC returns to >=
500/mcL
· (myelodysplastic syndrome) neutropenia AFTER 4 weeks of starting 10 mg daily:
stop lenalidomide for ANC < 500/mcL for >= 7 days OR ANC < 500 associated with
fever (>= 38.5 degrees Celsius); resume at reduced dose of 5 mg ORALLY once daily
when ANC returns to >= 500/mcL
· (myelodysplastic syndrome) neutropenia during treatment with 5 mg daily: stop
lenalidomide for ANC < 500/mcL for >= 7 days OR ANC < 500 associated with fever
(>= 38.5 degrees Celsius); resume at reduced dose of 5 mg ORALLY once EVERY
OTHER DAY when ANC returns to>= 500/mcL
· (myelodysplastic syndrome) thrombocytopenia WITHIN 4 weeks of starting 10 mg
daily, baseline platelets >= 100,000/mcL: stop lenalidomide for platelets < 50,000/mcL;
resume at reduced dose of 5 mg ORALLY once daily when platelets return to >=
50,000/mcL
· (myelodysplastic syndrome) thrombocytopenia WITHIN 4 weeks of starting 10 mg
daily, baseline platelets >= 60,000/mcL and < 100,000/mcL: stop lenalidomide when
platelets fall to 50% of baseline value; resume at reduced dose of 5 mg ORALLY once
daily when platelets return to at least 50,000/mcL
· (myelodysplastic syndrome) thrombocytopenia WITHIN 4 weeks of starting 10 mg
daily, baseline platelets < 60,000/mcL: stop lenalidomide when platelets fall to 50% of
baseline value; resume at reduced dose of 5 mg ORALLY once daily when platelets
return to at least 30,000/mcL
· (myelodysplastic syndrome) thrombocytopenia AFTER 4 weeks of starting 10 mg
daily: stop lenalidomide for platelets < 30,000/mcL OR < 50,000/mcL associated with
platelet transfusions; resume at reduced dose of 5 mg ORALLY once daily when platelets
return to at least 30,000/mcL without hemostatic failure
· (myelodysplastic syndrome) thrombocytopenia during treatment with 5 mg daily:
stop lenalidomide for platelets < 30,000/mcL OR < 50,000/mcL associated with platelet
transfusions; resume at reduced dose of 5 mg ORALLY once EVERY OTHER DAY
when platelets return to at least 30,000/mcL without hemostatic failure
· FDA Labeled Indications
· Multiple myeloma, in combination with dexamethasone, in patients who have
received at least 1 prior therapy
FDA Approval:
Adult, yes
Pediatric, no
Efficacy:
Adult, Evidence favors efficacy
Strength of Recommendation:
Adult, Class IIa
Strength of Evidence:

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Adult, Category B
· Myelodysplastic syndrome, Transfusion-dependent, deletion 5q abnormality, low or
intermediate-1 risk
FDA Approval:
Adult, yes
Pediatric, no
Efficacy:
Adult, Evidence favors efficacy
Strength of Recommendation:
Adult, Class IIa
Strength of Evidence:
Adult, Category B
· Non-FDA Labeled Indications
· Multiple myeloma, In combination with dexamethasone, first-line therapy
FDA Approval:
Adult, no
Pediatric, no
Efficacy:
Adult, Evidence favors efficacy
Strength of Recommendation:
Adult, Class IIa
Strength of Evidence:
Adult, Category B
Black Box WARNING
· POTENTIAL FOR HUMAN BIRTH DEFECTS
Lenalidomide is an analogue of thalidomide. Thalidomide is a known human
teratogen that causes severe life-threatening human birth defects. If lenalidomide is taken
during pregnancy, it may cause birth defects or death to an unborn baby. Females should
be advised to avoid pregnancy while taking lenalidomide.
SPECIAL PRESCRIBING REQUIREMENTS: Because of this potential toxicity
and to avoid fetal exposure to lenalidomide, lenalidomide is only available under a
special restricted distribution program. This program is called RevAssist(SM). Under this
program, only prescribers and pharmacists registered with the program are able to
prescribe and dispense the product. In addition, lenalidomide must only be dispensed to
patients who are registered and meet all the conditions of the the RevAssist(SM)
program. Please see the following information for prescribers, female patients, and male
patients about this restricted distribution program.
REVASSIST(SM) PROGRAM DESCRIPTION
PRESCRIBERS: Lenalidomide can be prescribed only by licensed prescribers who
are registered in the RevAssist(SM) program and understand the potential risk of

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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
lenalidomide therapy, during lenalidomide therapy, during dose interruptions and for 4
weeks following discontinuation of lenalidomide 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.
Two reliable forms of contraception must be used simultaneously unless continuous
abstinence from heterosexual sexual contact is the chosen method. 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 (ie, who have had menses at some time in the
preceding 24 consecutive months) are considered to be females of childbearing potential.
Before prescribing lenalidomide, FEMALES of childbearing potential should have
2 negative pregnancy tests (sensitivity of at least 50 mIU/mL). The first test should be
performed within 10 to 14 days, and the second test within 24 hours prior to prescribing
lenalidomide. A prescription for lenalidomide for a female of childbearing potential must
not be issued by the prescriber until negative pregnancy tests have been verified by the
prescriber.
For MALE patients, it is not known whether lenalidomide is present in the semen of
patients receiving the drug. Therefore, males receiving lenalidomide 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 ther pregnancy test or in her menstrual
bleeding. Lenalidomide treatment must be discontinued during this evaluation.
Pregnancy test results should be verified by the prescriber and the pharmacist prior
to dispensing any prescription.
If pregnancy does occur during lenalidomide treatment, lenalidomide must be
discontinued immediately.
Any suspected fetal exposure to lenalidomide should be reported to the FDA via the
MedWatch number at 1-800-FDA-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 evaluation and counseling.
FEMALE PATIENTS: Lenalidomide should be used in females of childbearing
potential only when the patient meets all of the following conditions (ie, she is unable to
become pregnant while on lenalidomide therapy):
she understands and can reliably carry out instructions.
she is capable of complying with the mandatory contraceptive measures, pregnancy
testing, patient registration, and patient survey as described in the RevAssist(SM)
program.

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she has received and understands both oral and written warnings of the potential
risks of taking lenalidomide 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, 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 (ie, who have had menses at some
time in the preceding 24 consecutive months) 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
lenalidomide therapy, during lenalidomide therapy, during dose interruptions and for 4
weeks after discontinuation of lenalidomide therapy.
she has had two negative pregnancy tests with a sensitivity of at least 50 mIU/mL,
within 10 to 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: Lenalidomide should be used in sexually active males when
the PATIENT MEETS ALL OF THE FOLLOWING CONDITIONS:
he understands and can reliably carry out instructions.
he is capable of complying with the mandatory contraceptive measures that are
appropriate for men, patient registration, and patient survey as described in the
RevAssist(SM) program.
he has received and understands both oral and written warnings of the potential
risks of taking lenalidomide and exposing a fetus to the drug.
he has received both oral and written warnings of the risk of possible contraception
failure and that it is unknown whether lenalidomide is present in semen. He has been
instructed that he must always use a latex condom during any sexual contact with females
of childbearing potential, even if he has undergone a successful vasectomy.
he acknowledges, in writing, his understanding of these warnings and of the need to
use a latex condom during any sexual contact with females of childbearing potential,
even if he has undergone a successful vasectomy. Females of childbearing potential are
considered to be sexually mature females who have not undergone a hysterectomy, have
not had a bilateral oophorectomy, or who have not been postmenopausal for at least 24
consecutive months (ie, who have had menses at any time in the preceding 24
consecutive months).
if the patient is between 12 and 18 years of age, his parent or legal guardian must
have read the educational material and agreed to ensure compliance with the above.
· HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA)
This drug is associated with 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

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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.
· DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM
This drug has demonstrated a significantly increased risk of deep venous
thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma who
were treated with lenalidomide combination 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 lenalidomide 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
· You can get the information about lenalidomide and the RevAssist(SM) program on
the internet at www. revlimid.com or by calling the manufacturer's toll free number 1-
888-423-5436 .
Contraindications/Warnings
· Contraindications
· pregnancy; category X, high potential for birth defects
· women of childbearing potential; unless adequate precautions taken to prevent
pregnancy, potential for birth defects
· hypersensitivity to lenalidomide or any of its components
· Precautions
· deep vein thrombosis; increased risk
· males, sexually active; must comply with mandatory contraception to prevent
pregnancy, potential for birth defects
· neutropenia; increased risk
· pulmonary embolism; increased risk
· thrombocytopenia; increased risk
· renal impairment; potential increased risk of toxicity
· Pregnancy Category
· X (FDA)
· Breast Feeding
· Thomson Lactation Rating: Infant risk cannot be ruled out.

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Drug Interactions
· Moderate
Digoxin (probable)
Adverse Effects
· COMMON
Cardiovascular: Peripheral edema (21.1%)
Dermatologic: Pruritus (41.9%), Rash (35.8%)
Endocrine metabolic: Hyperglycemia (15%), Hypokalemia (11.3%)
Gastrointestinal: Abdominal pain (12.2%), Constipation (38.7%), Diarrhea (48.6%),
Indigestion (13.9%), Loss of appetite (13.6%), Nausea (23.6%), Vomiting (10.1%),
Weight decreased (18.2%)
Hematologic: Leukopenia (8.1%)
Musculoskeletal: Arthralgia (21.6%), Backache (20.9%), Cramp (30.1%), Muscle
weakness (15%)
Neurologic: Dizziness (20.8%), Headache (19.6%), Insomnia (32.1%), Peripheral
neuropathy (8.1%), Tremor (19.7%)
Ophthalmic: Blurred vision (14.7%)
Psychiatric: Asthenia (23.4%), Fatigue (31.1%)
Renal: Dysuria (6.8% .)
Respiratory: Upper respiratory infection (14.9%)
Other: Fatigue (38.4%), Fever (23.1%)
· SERIOUS
Cardiovascular: Deep venous thrombosis (7.8)
Hematologic: Anemia (24.3 %), Febrile neutropenia (5.4%), Neutropenia,
Thrombocytopenia (16% to 61.5%)
Respiratory: Dyspnea (20.2%), Pneumonia (11.5%), Pulmonary embolism (3.2%)
Name Info
· US Trade Names
· Revlimid
· Class
· Immune Modulator
· Regulatory Status
· RX
· Generic Availability

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· No
Mechanism of Action/Pharmacokinetics
· Mechanism of Action
· Lenalidomide possesses immunomodulatory and antiangiogenic properties. Its exact
mechanism of action is unknown but it has been shown in vitro to affect inflammatory
cytokines and inhibit cell proliferation of various cell lines.
· Pharmacokinetics
· Absorption
Effect of food: no change in AUC, Cmax reduced by 36%
· Distribution
Protein binding: approximately 30%
· Excretion
Renal: approximately 67% unchanged
· Elimination Half Life
3 hours
Administration/Monitoring
· Administration
· Oral
Oral: do not break, chew, or open the capsules
Oral: take with water
· Monitoring
· Complete blood counts weekly for 8 weeks, then periodically thereafter
· Pregnancy tests in women of childbearing potential
· Renal function
· Signs and symptoms of thromboembolism (shortness of breath, chest pain, arm or leg
swelling)
· Trend in red blood cell transfusion requirement
How Supplied
· Revlimid
Oral Capsule: 5 MG, 10 MG, 15 MG, 25 MG
Toxicology

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· Clinical Effects
· LENALIDOMIDE
OVERDOSE: Data is limited. Toxic effects are likely an extension of adverse
effects. ADVERSE EFFECTS: Myelosuppression (neutropenia and thrombocytopenia)
can be severe. NEUTROPENIA: Median time to onset of grade 3 or 4 is 42 days (range:
14 to 411 days); median time to recovery is 17 days (range: 2 to 170 days).
THROMBOCYTOPENIA: Median time to onset of grade 3 or 4 is 8 days (range: 8 to
290 days); median time to recovery is 22 days (range: 5 to 224 days). OTHER: Edema,
dry skin, rash, urticaria, pruritus, hypothyroidism, hypokalemia, hypomagnesemia,
anorexia, diarrhea, constipation, nausea, vomiting, abdominal pain, dysuria, joint pain,
back pain, muscle cramps, pain in limb, insomnia, dizziness, headache, neuropathy,
fatigue, asthenia, nasopharyngitis, cough, dyspnea, epistaxis and fever.
· Treatment of Exposure
· LENALIDOMIDE
Decontamination: Activated charcoal.
Support: Treatment is symptomatic and supportive.
Myelosuppression: Filgrastim 5 mcg/kg/day subcutaneously, or sargramostim 250
mcg/m(2)/day infused over 4 hrs for severe neutropenia; platelets transfusion, protective
isolation as indicated.
Monitoring of patient: Monitor serial CBC with differential and platelets, fluid and
electrolytes (including magnesium), renal function and hepatic enzymes, signs and
symptoms of thromboembolism.
· Range of Toxicity
· LENALIDOMIDE
TOXICITY: Overdose data is limited. No lethal human dose has been established.
Doses of 30 mg/day were used in clinical studies. THERAPEUTIC DOSE: 10 mg/day
orally.
Clinical Teaching
· Adverse effects to a fetus may be caused by either male or female patients receiving
treatment with this drug. Emphasize the use of reliable contraception to patient. This
applies during treatment and up to 4 wks post-therapy.
· Advise patients to not donate sperm or blood during therapy and for 4 wks following
discontinuation of drug.
· This drug may cause peripheral edema, abdominal pain, constipation, diarrhea,
dyspepsia, loss of appetite, nausea, vomiting, weight loss, arthralgia, back pain, cramps,
muscle weakness, dizziness, headache, insomnia, tremor, blurred vision, asthenia,
fatigue, dysuria, fatigue, or fever.
· Patients are at an increased risk for deep venous thrombosis and pulmonary
embolism. Advise patient to report signs/symptoms of these adverse effects.

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· Instruct patients to report signs/symptoms of myelosuppression or peripheral
neuropathy.
· Patient should take drug with water.
Warranty and Disclaimer
The information above is for use only by healthcare professionals in conjunction with
clinical data and their professional judgment.
Copyright© THOMSON MICROMEDEX HEALTHCARE 1974-2007. All Rights
Reserved.
Copyright© THOMSON MICROMEDEX HEALTHCARE 1974-2007. All Rights
Reserved.

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