Lenalidomide (Revlimid)
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Lenalidomide (Revlimid)

REVLIMID
[lenalidomide]

WARNING

FETAL RISK, HEMATOLOGIC TOXICITY, and DEEP VEIN THROMBOSIS AND PULMONARY EMBOLISM

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 death to a developing baby. In women of childbearing potential, obtain 2 negative pregnancy tests before starting REVLIMID® treatment. Women of childbearing 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, and Medication Guide]. To avoid fetal exposure to lenalidomide, REVLIMID is only available under a restricted distribution program called “RevAssist®”).

Information about the RevAssist program is available at www.REVLIMID.com or by calling the manufacturer's toll-free number 1-888423-5436.

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].

Deep Vein Thrombosis and Pulmonary Embolism

REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with multiple myeloma who were treated with REVLIMID and dexamethasone 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 REVLIMID 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

DRUG DESCRIPTION

REVLIMID, a thalidomide analogue, is an immunomodulatory agent with antiangiogenic and antineoplastic properties. The chemical name is 3(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione and it has the following chemical structure:

REVLIMID [lenalidomide] Structural Formula Illustration

3-(4-amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl) piperidine-2,6-dione

The empirical formula for lenalidomide is C13H13N3O3, and the gram molecular weight is 259.3.

Lenalidomide is an off-white to pale-yellow solid powder. It is soluble in organic solvent/water mixtures, and buffered aqueous solvents. Lenalidomide is more soluble in organic solvents and low pH solutions. Solubility was significantly lower in less acidic buffers, ranging from about 0.4 to 0.5 mg/ml. Lenalidomide has an asymmetric carbon atom and can exist as the optically active forms S(-) and R(+), and is produced as a racemic mixture with a net optical rotation of zero.

REVLIMID is available in 2.5 mg, 5 mg, 10 mg, 15 mg and 25 mg capsules for oral administration. Each capsule contains lenalidomide as the active ingredient and the following inactive ingredients: lactose anhydrous, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. The 5 mg and 25 mg capsule shell contains gelatin, titanium dioxide and black ink. The 2.5 mg and 10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink. The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide and black ink.

What are the possible side effects of lenalidomide (Revlimid)?

Stop using lenalidomide and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • chest pain, sudden shortness of breath, coughing up blood;
  • pain or swelling in your arm, thigh, or calf;
  • easy bruising, unusual bleeding or weakness;
  • fever, chills, body aches, flu symptoms;
  • lower back pain, blood in your urine;
  • urinating less than usual or not at...

Read All Potential Side Effects and See Pictures of Revlimid »

What are the precautions when taking lenalidomide (Revlimid)?

Before taking lenalidomide, tell your doctor or pharmacist if you are allergic to it; or to thalidomide; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at a greater risk for side effects while using...

Read All Potential Precautions of Revlimid »

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Multiple Myeloma

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

Myelodysplastic Syndromes

REVLIMIDis 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.

DOSAGE AND ADMINISTRATION

REVLIMIDshould be taken orally at about the same time each day, either with or without food. REVLIMID capsules should be swallowed whole with water. The capsules should not be opened, broken, or chewed.

Multiple Myeloma

The recommended starting dose of REVLIMID is 25 mg once daily on Days 1-21 of repeated 28-day cycles. 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

When Platelets Recommended Course
Fall to <30,000/mcL Interrupt REVLIMID treatment, follow CBC weekly
Return to ≥ 30,000/mcL Restart REVLIMID at 15 mg daily
For each subsequent drop <30,000/mcL Interrupt REVLIMID treatment
Return to ≥ 30,000/mcL Resume REVLIMID at 5 mg less than the previous dose. Do not dose below 5 mg daily

Absolute Neutrophil counts (ANC)

Neutropenia in MM

When Platelets Recommended Course
Fall to <1000/mcL Interrupt REVLIMID treatment, add G-CSF, follow CBC weekly
Return to ≥ 1,000/mcL and neutropenia is the only toxicity Resume REVLIMID at 25 mg daily
Return to ≥ 1,000/mcL and if other toxicity Resume REVLIMID at 15 mg daily
For each subsequent drop <1,000/mcL Interrupt REVLIMID treatment
Return to ≥ 1,000/mcL Resume REVLIMID at 5 mg less than the
previous dose. Do not dose below 5 mg daily

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:

Table 1: Starting Dose Adjustment for Renal Impairment in Multiple Myeloma (Days 1 – 21 of each 28 day cycle)

Category Renal Function (Cockcroft-Gault) Dose
Moderate Renal Impairment CLcr 30-60 mL/min 10 mg Every 24 hours
Severe Renal Impairment CLcr <30 mL/min (not requiring dialysis) 15 mg Every 48 hours
End Stage Renal Disease CLcr <30 mL/min (requiring dialysis) 5 mg Once daily. On dialysis days, administer the dose following dialysis.

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

Myelodysplastic Syndromes

The recommended starting dose of REVLIMID is 10 mg daily. 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 baseline ≥ 100,000/mcL  
When Platelets Recommended Course
Fall to <50,000/mcL Interrupt REVLIMID treatment
Return to ≥ 50,000/mcL Resume REVLIMID at 5 mg daily
If baseline <100,000/mcL
When Platelets Recommended Course
Fall to 50% of the baseline value Interrupt REVLIMID treatment
If baseline ≥ 60,000/mcL and returns to ≥ 50,000/mcL Resume REVLIMID at 5 mg daily
If baseline <60,000/mcL and returns to ≥ 30,000/mcL Resume REVLIMID at 5 mg daily

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

When Platelets Recommended Course
<30,000/mcL or <50,000/mcL with platelet transfusions Interrupt REVLIMID treatment
Return to ≥ 30,000/mcL (without hemostatic failure) Resume REVLIMID at 5 mg daily

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 Recommended Course
<30,000/mcL or <50,000/mcL with platelet transfusions Interrupt REVLIMID treatment
Return to ≥ 30,000/mcL (without hemostatic failure) Resume REVLIMID at 2.5 mg daily

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 ≥ 1,000/mcL  
When Neutrophils Recommended Course
Fall to <750/mcL Interrupt REVLIMID treatment
Return to ≥ 1,000/mcL Resume REVLIMID at 5 mg daily
If baseline ANC <1,000/mcL  
When Neutrophils Recommended Course
Fall to <500/mcL Interrupt REVLIMID treatment
Return to ≥ 500/mcL Resume REVLIMID at 5 mg daily

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

When Neutrophils Recommended Course
<500/mcL for ≥ 7 days or <500/mcL associated with fever (≥ 38.5°C) Interrupt REVLIMID treatment
Return to ≥ 500/mcL Resume REVLIMID at 5 mg daily

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 Recommended Course
<500/mcL for ≥ 7 days or <500/mcL associated with fever (≥ 38.5°C) Interrupt REVLIMID treatment
Return to ≥ 500/mcL Resume REVLIMID at 2.5 mg daily

Other Grade 3 / 4 Toxicities in MDS

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 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:

Table 2: Starting Dose Adjustment for Renal Impairment in Myelodysplastic Syndromes (Days 1 – 28 of each 28 day cycle)

Category Renal Function (Cockcroft-Gault) Dose
Moderate Renal Impairment CLcr 30-60 mL/min 5 mg Every 24 hours
Severe Renal Impairment CLcr <30 mL/min (not requiring dialysis) 2.5 mg Every 24 hours
End Stage Renal Disease CLcr <30 mL/min (requiring dialysis) 2.5 mg once daily. On dialysis days, administer the dose following dialysis.

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

HOW SUPPLIED

Dosage Forms And Strengths

REVLIMID 2.5 mg, 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:

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

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

Storage And Handling

Care should be exercised in the handling of REVLIMID. REVLIMID capsules should not be opened or crushed. If a powder from REVLIMID contacts the skin, wash the skin immediately and thoroughly with soap and water. If REVLIMID contacts the mucous membranes, flush thoroughly with water.

Procedures for the proper handling and disposal of anticancer drugs should be considered. Several guidelines on the subject have been published.1-4

White and blue-green opaque hard capsules imprinted “REV” on one half and “2.5 mg” on the other half in black ink:

2.5 mg bottles of 28 (NDC 59572-402-28)
2.5 mg bottles of 100 (NDC 59572-402-00)

White opaque capsules imprinted “REV” on one half and “5 mg” on the other half in black ink:

5 mg bottles of 28 (NDC 59572-405-28)
5 mg bottles of 100 (NDC 59572-405-00)

Blue/green and pale yellow opaque capsules imprinted “REV” on one half and “10 mg” on the other half in black ink:

10 mg bottles of 28 (NDC 59572-410-28)
10 mg bottles of 100 (NDC 59572-410-00)

Powder blue and white opaque capsules imprinted “REV” on one half and “15 mg” on the other half in black ink:

15 mg bottles of 21 (NDC 59572-415-21)
15 mg bottles of 100 (NDC 59572-415-00)

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

25 mg bottles of 21 (NDC 59572-425-21)
25 mg bottles of 100 (NDC 59572-425-00)

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature].

Dispense no more than a 28-day supply.

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http: //www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. American Society of Health-System Pharmacists. ASHP Guidelines on Handling Hazardous Drugs: Am J Health-Syst Pharm. 2006;63: 1172-1193.

4. Polovich M., White JM, Kelleher LO (eds). Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed.) 2005. Pittsburgh, PA: Oncology Nursing Society.

Manufactured for: Celgene Corporation Summit, NJ 07901. Revised: 03/12

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following adverse reactions are described in detail in other labeling sections:

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trials Experience in Multiple Myeloma

Data were evaluated from 703 patients in two studies who received at least one dose of REVLIMID/dexamethasone (353 patients) or placebo/dexamethasone (350 patients).

In the REVLIMID/dexamethasone treatment group, 269 patients (76%) underwent at least one dose interruption with or without a dose reduction of REVLIMID compared to 199 patients (57%) in the placebo/dexamethasone treatment group. Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID/dexamethasone treatment group underwent at least one additional dose interruption with or without a dose reduction compared to 21% in the placebo/dexamethasone treatment group. Most adverse events and Grade 3/4 adverse events were more frequent in patients who received the combination of REVLIMID/dexamethasone compared to placebo/dexamethasone.

Tables 3, 4, and 5 summarize the adverse reactions reported for REVLIMID/dexamethasone and placebo/dexamethasone groups.

Table 3: Adverse Reactions Reported in ≥ 5% of Patients and with a ≥ 2% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups

System Organ Class/ Preferred Term REVLIMID/Dex*
(n=353)
n (%)
Placebo/Dex *
(n=350)
n (%)
Blood and lymphatic system disorders
Neutropenia % 149 (42.2) 22 (6.3)
Anemia @ 111 (31.4) 83 (23.7)
Thrombocytopenia @ 76 (21.5) 37 (10.6)
Leukopenia 28 (7.9) 4 (1.1)
Lymphopenia 19 (5.4) 5 (1.4)
General disorders and administration site conditions
Fatigue 155 (43.9) 146 (41.7)
Pyrexia 97 (27.5) 82 (23.4)
Peripheral edema 93 (26.3) 74 (21.1)
Chest Pain 29 ( 8.2) 20 (5.7)
Lethargy 24 ( 6.8) 8 (2.3)
Gastrointestinal disorders
Constipation 143 (40.5) 74 (21.1)
Diarrhea@ 136 (38.5) 96 (27.4)
Nausea @ 92 (26.1) 75 (21.4)
Vomiting @ 43 (12.2) 33 (9.4)
Abdominal Pain @ 35 (9.9) 22 (6.3)
Dry Mouth 25 (7.1) 13 (3.7)
Musculoskeletal and connective tissue disorders
Muscle cramp 118 (33.4) 74 (21.1)
Back pain 91 (25.8) 65 (18.6)
Bone Pain 48 (13.6) 39 (11.1)
Pain in Limb 42 (11.9) 32 (9.1)
Nervous system disorders
Dizziness 82 (23.2) 59 (16.9)
Tremor 75 (21.2) 26 (7.4)
Dysgeusia 54 (15.3) 34 (9.7)
Hypoaesthesia 36 (10.2) 25 (7.1)
Neuropathya 23 (6.5) 13 (3.7)
Respiratory, Thoracic and Mediastinal Disorders
Dyspnea 83 (23.5) 60 (17.1)
Nasopharyngitis 62 (17.6) 31 (8.9)
Pharyngitis 48 (13.6) 33 (9.4)
Bronchitis 40 (11.3) 30 (8.6)
Infectionsb and infestations
Upper respiratory tract infection 87 (24.6) 55 (15.7)
Pneumonia @ 48 (13.6) 29 (8.3)
Urinary Tract Infection 30 (8.5) 19 (5.4)
Sinusitis 26 (7.4) 16 (4.6)
Skin and subcutaneous system disorders
Rashc 75 (21.2) 33 (9.4)
Sweating Increased 35 (9.9) 25 (7.1)
Dry Skin 33 (9.3) 14 (4.0)
Pruritus 27 (7.6) 18 (5.1)
Metabolism and nutrition disorders
Anorexia 55 (15.6) 34 (9.7)
Hypokalemia 48 (13.6) 21 (6.0)
Hypocalcemia 31 (8.8) 10 (2.9)
Appetite Decreased 24 (6.8) 14 (4.0)
Dehydration 23 (6.5) 15 (4.3)
Hypomagnesaemia 24 (6.8) 10 (2.9)
Investigations
Weight Decreased 69 (19.5) 52 (14.9)
Eye disorders
Blurred vision 61 (17.3) 40 (11.4)
Vascular disorders
Deep vein thrombosis % 33 (9.3) 15 (4.3)
Hypertension 28 (7.9) 20 (5.7)
Hypotension 25 (7.1) 15 (4.3)
For all tables above:
n – Number of Patients
* - All Treatment Emergent AEs with ≥ 5% of Patients in REVLIMID/ Dex and at Least 2% Difference in Proportion between the Two Arms -(Safety population)
# - All Treatment Emergent Grades 3 and 4 AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms - (Safety population)
& - All Treatment Emergent Serious AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms -(Safety population)
@ - ADRs with Death as an outcome
% - ADRs which were considered to be life threatening (if the outcome of the event was death, it is included with death cases)
a- All PTs under the MedDRA SMQ of Neuropathy of a peripheral sensory nature will be considered listed
b- All PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
c-All PTs under HLT of Rash will be considered listed
Dex=dexamethasone
Median duration of exposure among patients treated with REVLIMID/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse events between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone.

Table 4: Grade 3/4 Adverse Reactions Reported in ≥ 2% Patients and With a ≥ 1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone groups

System Organ Class/ Preferred Term REVLIMID/Dex#
(n=353)
n (%)
Placebo/Dex#
(n=350)
n (%)
Blood and lymphatic system disorders
Neutropenia % 118 (33.4) 12 (3.4)
Thrombocytopenia @ 43 (12.2) 22 (6.3)
Anemia @ 35 (9.9) 20 (5.7)
Leukopenia 14 (4.0) 1 (0.3)
Lymphopenia 10 (2.8) 4 (1.1)
Febrile Neutropenia % 8 (2.3) 0 (0.0)
General disorders and administration site conditions
Fatigue 23 (6.5) 17 (4.9)
Vascular disorders
Deep vein thrombosis % 29 (8.2) 12 (3.4)
Infectionsb and infestations
Pneumonia @ 30 (8.5) 19 (5.4)
Urinary Tract Infection 5 (1.4) 1 (0.3)
Metabolism and nutrition disorders
Hypokalemia 17 (4.8) 5 (1.4)
Hypocalcemia 13 (3.7) 6 (1.7)
Hypophosphatemia 9 (2.5) 0 (0.0)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism@ 14 (4.0) 3 (0.9)
Respiratory Distress @ 4 (1.1) 0 (0.0)
Musculoskeletal and connective tissue disorders
Muscle weakness 20 (5.7) 10 (2.9)
Gastrointestinal disorders
Diarrhea @ 11 (3.1) 4 (1.1)
Constipation 7 (2.0) 1 (0.3)
Nausea @ 6 (1.7) 2 (0.6)
Cardiac disorders
Atrial fibrillation @ 13 (3.7) 4 (1.1)
Tachycardia 6 (1.7) 1 (0.3)
Cardiac Failure Congestive @ 5 (1.4) 1 (0.3)
Nervous System disorders
Syncope 10 (2.8) 3 (0.9)
Dizziness 7 (2.0) 3 (0.9)
Eye Disorders
Cataract 6 (1.7) 1 (0.3)
Cataract Unilateral 5 (1.4) 0 (0.0)
Psychiatric Disorder
Depression 10 (2.8) 6 (1.7)
For all tables above:
n – Number of Patients
* - All Treatment Emergent AEs with ≥ 5% of Patients in REVLIMID/ Dex and at Least 2% Difference in Proportion between the Two Arms -(Safety population)
# - All Treatment Emergent Grades 3 and 4 AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms - (Safety population)
& - All Treatment Emergent Serious AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms -(Safety population)
@ - ADRs with Death as an outcome
% - ADRs which were considered to be life threatening (if the outcome of the event was death, it is included with death cases)
a- All PTs under the MedDRA SMQ of Neuropathy of a peripheral sensory nature will be considered listed
b- All PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
c-All PTs under HLT of Rash will be considered listed
Dex=dexamethasone
Median duration of exposure among patients treated with REVLIMID/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse events between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone.

Table 5: Serious Adverse Reactions Reported in ≥ 1% Patients and With a ≥ 1% Difference in Proportion of Patients Between the REVLIMID/dexamethasone and Placebo/dexamethasone Groups

System Organ Class/ Preferred Term REVLIMID/Dex&
(n=353)
n (%)
Placebo/Dex&
(n=350)
n (%)
Blood and lymphatic system disorders
Febrile Neutropenia% 6 (1.7) 0 (0.0)
Vascular disorders
Deep vein thrombosis% 26 (7.4) 11 (3.1)
Infectionsb and infestations
Pneumonia @ 33 (9.3) 21 (6.0)
Respiratory, thoracic, and mediastinal disorders
Pulmonary embolism@ 13 (3.7) 3 (0.9)
Cardiac disorders
Atrial fibrillation @ 11 (3.1) 2 (0.6)
Cardiac Failure Congestive @ 5 (1.4) 0 (0.0)
Nervous system disorders
Cerebrovascular accident @ 7 (2.0) 3 (0.9)
Gastrointestinal disorders
Diarrhea @ 6 (1.7) 2 (0.6)
Musculoskeletal and connective tissue disorders
Bone Pain 4 (1.1) 0 (0.0)
For all tables above:
n – Number of Patients
* - All Treatment Emergent AEs with ≥ 5% of Patients in REVLIMID/ Dex and at Least 2% Difference in Proportion between the Two Arms -(Safety population)
# - All Treatment Emergent Grades 3 and 4 AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms - (Safety population)
& - All Treatment Emergent Serious AEs with ≥ 1% Patients in REVLIMID/ Dex and at Least 1% Difference in Proportion between the Two Arms -(Safety population)
@ - ADRs with Death as an outcome
% - ADRs which were considered to be life threatening (if the outcome of the event was death, it is included with death cases)
a- All PTs under the MedDRA SMQ of Neuropathy of a peripheral sensory nature will be considered listed
b- All PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
c-All PTs under HLT of Rash will be considered listed
Dex=dexamethasone
Median duration of exposure among patients treated with REVLIMID/dexamethasone was 44 weeks while median duration of exposure among patients treated with placebo/dexamethasone was 23 weeks. This should be taken into consideration when comparing frequency of adverse events between two treatment groups REVLIMID/dexamethasone vs. placebo/dexamethasone.

Venous Thromboembolism

Deep Vein Thrombosis and Pulmonary Embolism

[see WARNINGS AND PRECAUTIONS]

Deep vein thrombosis (DVT) was reported as a serious adverse drug reaction (7.4%) or Grade 3/4 (8.2%) at a higher rate in the REVLIMID/dexamethasone group compared to 3.1 % and 3.4% in the placebo/dexamethasone group, respectively. Discontinuations due to DVT adverse reactions were reported at comparable rates between groups.

Pulmonary embolism (PE) was reported as a serious adverse drug reaction including Grade 3/4 (3.7%) at a higher rate in the REVLIMID/dexamethasone group compared to 0.9% in the placebo/dexamethasone group. Discontinuations due to PE adverse reactions were reported at comparable rates between groups.

Other Adverse Reactions

In these clinical studies of REVLIMID in patients with multiple myeloma, the following adverse drug reactions (ADRs) not described above that occurred at ≥ % rate and of at least twice of the placebo percentage rate were reported:

Blood and lymphatic system disorders: pancytopenia, autoimmune hemolytic anemia

Cardiac disorders: bradycardia, myocardial infarction, angina pectoris

Endocrine disorders: hirsutism

Eye disorders: blindness, ocular hypertension

Gastrointestinal disorders: gastrointestinal hemorrhage, glossodynia

General disorders and administration site conditions: malaise

Investigations: liver function tests abnormal, alanine aminotransferase increased

Nervous system disorders: cerebral ischemia

Psychiatric disorders: mood swings, hallucination, loss of libido

Reproductive system and breast disorders: erectile dysfunction

Respiratory, thoracic and mediastinal disorders: cough, hoarseness

Skin and subcutaneous tissue disorders: exanthem, skin hyperpigmentation

Clinical Trials Experience in Myelodysplastic Syndromes

A total of 148 patients received at least 1 dose of 10 mg REVLIMID in the del 5q MDS clinical study. At least one adverse event was reported in all of the 148 patients who were treated with the 10 mg starting dose of REVLIMID. The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.

Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events. The next most common adverse events observed were diarrhea (48.6%; 72/148), pruritus (41.9%; 62/148), rash (35.8%; 53/148) and fatigue (31.1%; 46/148). Table 6 summarizes the adverse events that were reported in ≥ 5% of the REVLIMID treated patients in the del 5q MDS clinical study. Table 7 summarizes the most frequently observed Grade 3 and Grade 4 adverse reactions regardless of relationship to treatment with REVLIMID. In the single-arm studies conducted, it is often not possible to distinguish adverse events that are drug-related and those that reflect the patient's underlying disease.

Table 6: Summary of Adverse Events Reported in ≥ 5% of the REVLIMID Treated Patients in del 5q MDS Clinical Study

System organ class/Preferred terma 10 mg Overall
(N=148)
Patients with at least one adverse event 148 (100.0)
Blood and Lymphatic System Disorders
  Thrombocytopenia 91 (61.5)
  Neutropenia 87 (58.8)
  Anemia 17 (11.5)
  Leukopenia 12 (8.1)
  Febrile Neutropenia 8 (5.4)
Skin and Subcutaneous Tissue Disorders 
  Pruritus 62 (41.9)
  Rash 53 (35.8)
  Dry Skin 21 (14.2)
  Contusion 12 (8.1)
  Night Sweats 12 (8.1)
  Sweating Increased 10 (6.8)
  Ecchymosis 8 (5.4)
  Erythema 8 (5.4)
Gastrointestinal Disorders
  Diarrhea 72 (48.6)
  Constipation 35 (23.6)
  Nausea 35 (23.6)
  Abdominal Pain 18 (12.2)
  Vomiting 15 (10.1)
  Abdominal Pain Upper 12 (8.1)
  Dry Mouth 10 (6.8)
  Loose Stools 9 (6.1)
Respiratory, Thoracic and Mediastinal Disorders
  Nasopharyngitis 34 (23.0)
  Cough 29 (19.6)
  Dyspnea 25 (16.9)
  Pharyngitis 23 (15.5)
  Epistaxis 22 (14.9)
  Dyspnea Exertional 10 (6.8)
  Rhinitis 10 (6.8)
  Bronchitis 9 (6.1)
General Disorders and Administration Site Conditions
  Fatigue 46 (31.1)
  Pyrexia  31 (20.9)
  Edema Peripheral 30 (20.3)
  Asthenia 22 (14.9)
  Edema 15 (10.1)
  Pain 10 (6.8)
  Rigors 9 (6.1)
  Chest Pain 8 (5.4)
Musculoskeletal and Connective Tissue Disorders
  Arthralgia 32 (21.6)
  Back Pain 31 (20.9)
  Muscle Cramp 27 (18.2)
  Pain in Limb 16 (10.8)
  Myalgia 13 (8.8)
  Peripheral Swelling 12 (8.1)
Nervous System Disorders 
  Dizziness 29 (19.6)
  Headache 29 (19.6)
  Hypoesthesia 10 (6.8)
  Dysgeusia 9 (6.1)
  Peripheral Neuropathy 8 (5.4)
Infections and Infestations
  Upper Respiratory Tract Infection 22 (14.9)
  Pneumonia 17 (11.5)
  Urinary Tract Infection 16 (10.8)
  Sinusitis 12 (8.1)
  Cellulitis 8 (5.4)
Metabolism and Nutrition Disorders
  Hypokalemia 16 (10.8)
  Anorexia 15 (10.1)
  Hypomagnesemia 9 (6.1)
Investigations
  Alanine Aminotransferase Increased 12 (8.1)
Psychiatric Disorders
  Insomnia 15 (10.1)
  Depression 8 (5.4)
Renal and Urinary Disorders
  Dysuria 10 (6.8)
Vascular Disorders
  Hypertension 9 ( 6.1)
Endocrine Disorders
  Acquired Hypothyroidism 10 (6.8)
Cardiac Disorders
  Palpitations 8 (5.4)
a System organ classes and preferred terms are coded using the MedDRA dictionary. System organ classes and preferred terms are listed in descending order of frequency for the Overall column. A patient with multiple occurrences of an AE is counted only once in the AE category.

Table 7: Most Frequently Observed Grade 3 and 4 Adverse Events1 Regardless of Relationship to Study Drug Treatment

Preferred term2 10 mg (N=148)
Patients with at least one Grade 3/4 AE 131 (88.5)
  Neutropenia 79 (53.4)
  Thrombocytopenia 74 (50.0)
  Pneumonia 11 (7.4)
  Rash 10 (6.8)
  Anemia 9 (6.1)
  Leukopenia 8 (5.4)
  Fatigue 7 (4.7)
  Dyspnea 7 (4.7)
  Back Pain 7 (4.7)
  Febrile Neutropenia 6 (4.1)
  Nausea 6 (4.1)
  Diarrhea 5 (3.4)
  Pyrexia 5 (3.4)
  Sepsis 4 (2.7)
  Dizziness 4 (2.7)
  Granulocytopenia 3 (2.0)
  Chest Pain 3 (2.0)
  Pulmonary Embolism 3 (2.0)
  Respiratory Distress 3 (2.0)
  Pruritus 3 (2.0)
  Pancytopenia 3 (2.0)
  Muscle Cramp 3 (2.0)
  Respiratory Tract Infection 2 (1.4)
  Upper Respiratory Tract Infection 2 (1.4)
  Asthenia 2 (1.4)
  Multi-organ Failure 2 (1.4)
  Epistaxis 2 (1.4)
  Hypoxia 2 (1.4)
  Pleural Effusion 2 (1.4)
  Pneumonitis 2 (1.4)
  Pulmonary Hypertension 2 (1.4)
  Vomiting 2 (1.4)
  Sweating Increased 2 (1.4)
  Arthralgia 2 (1.4)
  Pain in Limb 2 (1.4)
  Headache 2 (1.4)
  Syncope 2 (1.4)
1Adverse events with frequency ≥ 1% in the 10 mg Overall group. Grade 3 and 4 are based on National Cancer Institute Common Toxicity Criteria version 2.
2 Preferred Terms are coded using the MedDRA dictionary. A patient with multiple occurrences of an AE is counted only once in the Preferred Term category.

In other clinical studies of REVLIMID in MDS patients, the following serious adverse events (regardless of relationship to study drug treatment) not described in Table 6 or 7 were reported:

Blood and lymphatic system disorders: warm type hemolytic anemia, splenic infarction, bone marrow depression, coagulopathy, hemolysis, hemolytic anemia refractory anemia

Cardiac disorders: cardiac failure congestive, atrial fibrillation, angina pectoris, cardiac arrest, cardiac failure, cardio-respiratory arrest, cardiomyopathy, myocardial infarction, myocardial ischemia, atrial fibrillation aggravated, bradycardia, cardiogenic shock, pulmonary edema supraventricular arrhythmia , tachyarrhythmia, ventricular dysfunction

Ear and labyrinth disorders: vertigo

Endocrine disorders: Basedow's disease

Gastrointestinal disorders: gastrointestinal hemorrhage, colitis ischemic, intestinal perforation, rectal hemorrhage, colonic polyp, diverticulitis, dysphagia, gastritis, gastroenteritis , gastroesophageal reflux disease, obstructive inguinal hernia, irritable bowel syndrome, melena, pancreatitisdue to biliary obstruction, pancreatitis, perirectal abscess, small intestinal obstruction, upper gastrointestinal hemorrhage

General disorders and administration site conditions: disease progression, fall, gait abnormal, intermittent pyrexia, nodule, rigors, sudden death

Hepatobiliary disorders: hyperbilirubinemia, cholecystitis, acute cholecystitis, hepatic failure

Immune system disorders: hypersensitivity

Infections and infestationsinfection bacteremia, central line infection, clostridial infection, ear infection Enterobacter sepsis, fungal infection herpes viral infection NOS, influenza, kidney infection Klebsiella sepsis, lobar pneumonia , localized infection, oral infection, Pseudomonasinfection, septic shock, sinusitis acute sinusitis, Staphylococcal infection, urosepsis

Injury, poisoning and procedural complications: femur fracture, transfusion reaction, cervical vertebral fracture, femoral neck fracture, fractured pelvis, hip fracture, overdose, post procedural hemorrhage, rib fracture, road traffic accident, spinal compression fracture

Investigations: blood creatinine increased, hemoglobin decreased, liver function tests abnormal, troponin I increased

Metabolism and nutrition disorders: dehydration, gout, hypernatremia, hypoglycemia

Musculoskeletal and connective tissue disorders: arthritis, arthritis aggravated, gouty arthritis, neck pain, chondrocalcinosis pyrophosphate

Neoplasms benign, malignant and unspecified: acute leukemia, acute myeloid leukemia, bronchoalveolar carcinoma, lung cancer metastatic, lymphoma, prostate cancer metastatic

Nervous system disorders: cerebrovascular accident, aphasia, cerebellar infarction, cerebral infarction, depressed level of consciousness, dysarthria, migraine, spinal cord compression, subarachnoid hemorrhage, transient ischemic attack

Psychiatric disorders: confusional state

Renal and urinary disorders: renal failure, hematuria, renal failure acute, azotemia, calculus ureteric, renal mass

Reproductive system and breast disorders: pelvic pain

Respiratory, thoracic and mediastinal disorders: bronchitis, chronic obstructive airways disease exacerbated, respiratory failure, dyspneaexacerbated, interstitial lung disease, lung infiltration, wheezing

Skin and subcutaneous tissue disorders: acute febrile neutrophilic dermatosis

Vascular system disorders: deep vein thrombosis, hypotension, aortic disorder, ischemia, thrombophlebitis superficial, thrombosis

Postmarketing Experience

The following adverse drug reactions have been identified from the worldwide post-marketing experience with REVLIMID. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Allergic conditions (angioedema, SJS, TEN), tumor lysis syndrome (TLS) and tumor flare reaction (TFR), pneumonitis, and transient abnormal liver laboratory tests. [see WARNINGS AND PRECAUTIONS Section].

Read the Revlimid (lenalidomide) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Results from human in vitro metabolism studies and nonclinical studies show that REVLIMID is neither metabolized by nor inhibits or induces the cytochrome P450 pathway suggesting that lenalidomide is not likely to cause or be subject to P450-based metabolic drug interactions in man.

In vitrostudies demonstrate that lenalidomide is not a substrate of multidrug resistance proteins MRP1, MRP2, or MRP3 nor a substrate of organic anion and cation uptake transporters OAT1, OAT3, OATP1B1 or OCT1.

In vitro, lenalidomide is a substrate, but is not an inhibitor of P-glycoprotein (P-gp).

Digoxin

When digoxin was co-administered with multiple doses of REVLIMID (10 mg/day) the digoxin Cmax and AUC0-. were increased by 14%. Periodic monitoring of digoxin plasma levels, in accordance with clinical judgment and based on standard clinical practice in patients receiving this medication, is recommended during administration of REVLIMID.

Warfarin

Co-administration of multiple dose REVLIMID (10 mg) with single dose warfarin (25 mg) had no effect on the pharmacokinetics of total lenalidomide or R- and S-warfarin. Expected changes in laboratory assessments of PT and INR were observed after warfarin administration, but these changes were not affected by concomitant REVLIMID administration. It is not known whether there is an interaction between dexamethasone and warfarin. Close monitoring of PT and INR is recommended in multiple myeloma patients taking concomitant warfarin.

Concomitant Therapies That May Increase the Risk of Thrombosis

Erythropoietic agents, or other agents that may increase the risk of thrombosis, such as estrogen containing therapies, should be used with caution in multiple myeloma patients receiving lenalidomide with dexamethasone. [see WARNINGS AND PRECAUTIONS]

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Fetal 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 dose interruptions and for at least 4 weeks after completing therapy.

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

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: Clinical data has demonstrated the presence of lenalidomide in human semen. Male patients taking REVLIMID should not donate sperm.

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 evaluation.

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 evaluation 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:

  • 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 program.
  • he has received and understands both oral and written warnings of the potential risks of taking REVLIMID 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 known that 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. 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 (i.e., who have had menses at any time in the preceding 24 consecutive months).
  • 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.
  • if the patient is between 12 and 18 years of age, his parent or legal guardian must have read the educational materials and agreed to ensure compliance with the above.

Hematologic Toxicity

REVLIMID can cause significant neutropenia and thrombocytopenia. Patients taking REVLIMID for MDS should have their complete blood counts monitored weekly for the first 8 weeks and at least monthly thereafter. Patients taking REVLIMID for MM should have their complete blood counts monitored every 2 weeks for the first 12 weeks and then monthly thereafter. Patients may require dose interruption and/or dose reduction [see DOSAGE AND ADMINISTRATION].

Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the MDS study. In the 48% of patients who developed Grade 3 or 4 neutropenia, the median time to onset was 42 days (range, 14-411 days), and the median time to documented recovery was 17 days (range, 2-170 days). In the 54% of patients who developed Grade 3 or 4 thrombocytopenia, the median time to onset was 28 days (range, 8-290 days), and the median time to documented recovery was 22 days (range, 5-224 days [see BOXED WARNINGand DOSAGE AND ADMINISTRATION].

In the pooled multiple myeloma studies Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID and dexamethasone than in patients treated with dexamethasone alone [see ADVERSE REACTIONS].

Deep Vein Thrombosis and Pulmonary Embolism

Venous thromboembolic events (predominantly deep venous thrombosis and pulmonary embolism) have occurred in patients with multiple myeloma treated with lenalidomide combination therapy [see BOXED WARNING] and patients with MDS treated with lenalidomide monotherapy. A significantly increased risk of DVT and PE was observed in patients with multiple myeloma who were treated with REVLIMID and dexamethasone therapy in a clinical trial [see BOXED WARNING]. It is not known whether prophylactic anticoagulation or antiplatelet therapy prescribed in conjunction with REVLIMID 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.

Allergic Reactions

Angioedema and serious dermatologic reactions including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported. These events can be fatal. Patients with a prior history of Grade 4 rash associated with thalidomide treatment should not receive REVLIMID. REVLIMID interruption or discontinuation should be considered for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema, Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected and should not be resumed following discontinuation for these reactions.

REVLIMID capsules contain lactose. Risk-benefit of REVLIMID treatment should be evaluated in patients with lactose intolerance.

Tumor Lysis Syndrome

Fatal instances of tumor lysis syndrome have been reported during treatment with lenalidomide. The patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

Tumor Flare Reaction

Tumor flare reaction has occurred during investigational use of lenalidomide for CLL and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash. Treatment of CLL or lymphoma with lenalidomide outside of a well-monitored clinical trial is discouraged.

Hepatotoxicity

Cases of transient liver laboratory abnormalities (predominantly transaminases) were reported in patients treated with lenalidomide. Treatment with lenalidomide should be interrupted and restarted once the levels return to baseline. Successful re-challenge without recurrence of liver laboratory elevation was reported in some patients.

Second Primary Malignancies

Patients with multiple myeloma treated with lenalidomide in studies including melphalan and stem cell transplantation had a higher incidence of second primary malignancies, particularly acute myelogenous leukemia (AML) and Hodgkin lymphoma, compared to patients in the control arms who received similar therapy but did not receive lenalidomide. Monitor patients for the development of second malignancies. Take into account both the potential benefit of lenalidomide and the risk of second primary malignancies when considering treatment with lenalidomide.

Patient Counseling Information

See Medication Guide

Importance of Preventing Pregnancy

Females of Childbearing Potential

Patients must be counseled on lenalidomide's potential risk of teratogenicity due to its structural similarity to thalidomide and data from an embryofetal development study showing treatment with lenalidomide produced malformations in the offspring of female monkeys who received the drug during pregnancy.

REVLIMID treatment should only be initiated in females of childbearing potential following a negative pregnancy test. Females of childbearing potential must be informed 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 therapy 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 condom, diaphragm and cervical cap. Patient must be instructed 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. The patient understands that if her doctor is not available, she can call 1-888-668-2528 for information on emergency contraception [see Use In Specific Populations].

REVLIMID treatment should only be initiated in a female not of childbearing potential if she confirms that she is not now pregnant, nor of childbearing potential as she has been postmenopausal naturally for at least 24 months (been through the change of life); or she has had a hysterectomy or bilateral oophorectomy. The patient or guardian certifies that a prepubertal female child is not now pregnant, nor is of childbearing potential as menstruation has not yet begun, and/or the child will not be engaging in heterosexual sexual contact for at least 4 weeks before REVLIMID therapy, during therapy, during therapy interruption and for at least 4 weeks after stopping REVLIMID therapy.

REVLIMID treatment should only be initiated in men who agree to either completely abstain from sexual contact with women who are pregnant or able to become pregnant, or use a latex condom every time he engages in any sexual contact with women who are pregnant or may become pregnant. The patient should inform his doctor if he has had unprotected sexual contact with a woman who can become pregnant. He understands that if his doctor is not available, he can call 1-888-668-2528 for information on emergency contraception.

Hematologic Toxicity

REVLIMID is associated with significant neutropenia and thrombocytopenia [see BOXED WARNINGS and WARNINGS AND PRECAUTIONS]

Deep Vein Thrombosis and Pulmonary Embolism

REVLIMID/dexamethasone has demonstrated significant increased risk of DVT and PE in patients with multiple myeloma [see BOXED WARNINGS and WARNINGS AND PRECAUTIONS]

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.

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.

Nonclinical Toxicology

Carcinogenesis, mutagenesis, impairment of fertility

Carcinogenicity

Carcinogenicity studies with lenalidomide have not been conducted.

Mutagenesis

Lenalidomide did not induce mutation in the Ames test, chromosome aberrations in cultured human peripheral blood lymphocytes, or mutation at the thymidine kinase (tk) locus of mouse lymphoma L5178Y cells. Lenalidomide did not increase morphological transformation in Syrian Hamster Embryo assay or induce micronuclei in the polychromatic erythrocytes of the bone marrow of male rats.

Fertility

A fertility and early embryonic development study in rats, with administration of lenalidomide up to 500 mg/kg (approximately 200 times the human dose of 25 mg, based on body surface area) produced no parental toxicity and no adverse effects on fertility.

Reproductive and Developmental Toxicity

Lenalidomide had an embryocidal effect in rabbits at a dose of 50 mg/kg (approximately 120 times the human dose of 10 mg based on body surface area).

In an embryofetal developmental toxicity study in monkeys, teratogenicity, including thalidomide-like limb defects, occurred in offspring when pregnant monkeys received oral lenalidomide during organogenesis at doses approximately 0.17-times the maximum recommended human dose (MRHD) of 25 mg, based on body surface area.

A pre- and post-natal development study in rats revealed few adverse effects on the offspring of female rats treated with lenalidomide at doses up to 500 mg/kg (approximately 200 times the human dose of 25 mg based on body surface area). The male offspring exhibited slightly delayed sexual maturation and the female offspring had slightly lower body weight gains during gestation when bred to male offspring.

Use In Specific Populations

Pregnancy

Pregnancy Category X: [see BOXED WARNINGS and CONTRAINDICATIONS]

REVLIMID can cause fetal harm when administered to a pregnant woman. REVLIMID is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women. However, in an animal study, lenalidomide caused thalidomide-type limb defects in monkey offspring. 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 hazard to a fetus.

If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure to REVLIMID must be reported to the FDA via the MedWatch program at 1-800-332-1088 and also to Celgene Corporation at 1-888-423-5436.

In an embryofetal developmental toxicity study in monkeys, teratogenicity, including thalidomide-like limb defects, occurred in offspring when pregnant monkeys received oral lenalidomide during organogenesis at doses approximately 0.17 times the maximum recommended human dose (MRHD) of 25 mg, based on body surface area. Similar studies in pregnant rabbits and rats at 20 times and 200 times the MRHD respectively, produced embryolethality in rabbits and no adverse reproductive effects in rats. In another study, pregnant rats received lenalidomide from organogenesis through lactation, some delay in sexual maturation occurred in male offspring. As with thalidomide, the rat model may not adequately address the full spectrum of potential human embryofetal developmental effects for lenalidomide.

Females of childbearing potential must use effective means of contraception for 28 days before therapy, during lenalidomide therapy and dose interruptions, and for 28 days following discontinuation of lenalidomide therapy, or continually abstain from reproductive heterosexual sexual intercourse. Because of the increased risk of VTE in patients with multiple myeloma taking lenalidomide and dexamethasone, and to a lesser extent patients with MDS taking lenalidomide monotherapy, and because there is an increased risk of VTE in patients taking combined oral contraceptive pills, physicians should discuss the risk/benefit of contraceptive methods with their patients

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.

Pediatric use

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

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.

REVLIMID has been used in del 5q MDS clinical trials in patients up to 95 years of age.

Of the 148 patients with del 5q MDS enrolled in the major study, 38% were age 65 and over, while 33% were age 75 and over. Although the overall frequency of adverse events (100%) was the same in patients over 65 years of age as in younger patients, the frequency of serious adverse events was higher in patients over 65 years of age than in younger patients (54% vs. 33%). A greater proportion of patients over 65 years of age discontinued from the clinical studies because of adverse events than the proportion of younger patients (27% vs.16%). No differences in efficacy were observed between patients over 65 years of age and younger patients.

Since elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Monitor renal function.

Renal Impairment

Since lenalidomide 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 (CLcr 30-60 mL/min) or severe renal impairment (CLcr < 30 mL/min) and in patients on dialysis [see DOSAGE AND ADMINISTRATION].

Hepatic Impairment

No study has been conducted in patients with hepatic impairment. The elimination of unchanged lenalidomide is predominantly by the renal route.

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There is no specific experience in the management of lenalidomide overdose in patients; although in dose-ranging studies, some patients were exposed to up to 150 mg and in single-dose studies, some patients were exposed to up to 400 mg.

In studies, the dose-limiting toxicity was essentially hematological. In the event of overdose, supportive care is advised.

CONTRAINDICATIONS

Pregnancy

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 dose interruptions , 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 evaluation and counseling.

Allergic 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].

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of action

The mechanism of action of lenalidomide remains to be fully characterized. Lenalidomide possesses immunomodulatory, antiangiogenic, and antineoplastic properties. Experiments have demonstrated that lenalidomide inhibits the growth of cells derived from patients with multiple myeloma and del (5q) myelodysplastic syndromes in vitro. Lenalidomide causes a delay in tumor growth in some in vivo nonclinical hematopoietic tumor models, including multiple myeloma. Lenalidomide inhibits the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), from peripheral blood mononuclear cells. Lenalidomide also inhibited the expression of cyclooxygenase-2 (COX2) but not COX-1 in vitro.

Pharmacokinetics

Absorption

Lenalidomide is rapidly absorbed following oral administration. Following single and multiple doses of REVLIMID in patients with MM or MDS the maximum plasma concentrations occurred between 0.5 and 6.0 hours post-dose. The single and multiple dose pharmacokinetic disposition of lenalidomide is linear with AUC and Cmax values increasing proportionally with dose. Multiple dosing at the recommended dose-regimen does not result in drug accumulation.

Systemic exposure (AUC) of lenalidomide in MM and MDS patients with normal or mild renal function (CLcr ≥ 60 mL/min) is approximately 60% higher as compared to young healthy male subjects.

Administration of a single 25 mg dose of REVLIMID with a high-fat meal in healthy subjects reduces the extent of absorption, with an approximate 20% decrease in AUC and 50% decrease in Cmax. In the trials where the efficacy and safety were established for REVLIMID, the drug was administered without regard to food intake. REVLIMID can be administered with or without food.

Distribution

In vitro (14C)-lenalidomide binding to plasma proteins is approximately 30%.

Metabolism

Lenalidomide -undergoes limited metabolism. Unchanged lenalidomide is the predominant circulating component in humans. Two identified metabolites are hydroxy-lenalidomide and N-acetyl-lenalidomide; each constitutes less than 5% of parent levels in circulation.

Elimination

Elimination is primarily renal. Following a single oral administration of [14C]-lenalidomide (25 mg) to healthy subjects, approximately 90% and 4% of the radioactive dose is eliminated within ten days in urine and feces, respectively. Approximately 82% of the radioactive dose is excreted as lenalidomide in the urine within 24 hours. Hydroxy-lenalidomide and N-acetyl-lenalidomide represent 4.59% and 1.83% of the excreted dose, respectively. The renal clearance of lenalidomide exceeds the glomerular filtration rate.

The mean half-life of lenalidomide is 3 hours in healthy subjects and 3 to 5 hours in patients with multiple myeloma or MDS.

Special Populations

Patients with Renal Impairment: The pharmacokinetics of lenalidomide were studied in patients with renal impairment due to nonmalignant conditions. In this study, 5 patients with mild renal impairment (creatinine clearance 57-74 mL/min), 6 patients with moderate renal impairment (creatinine clearance 33-46 mL/min), 6 patients with severe renal impairment (creatinine clearance 17-29 mL/min), and 6 patients with end stage renal disease requiring dialysis were administered a single oral 25-mg dose of REVLIMID. As a control group comparator, 7 healthy subjects of similar age with normal renal function (creatinine clearance 83-145 mL/min) were also administered a single oral 25-mg dose of REVLIMID. As creatinine clearance decreased from mild to severe impairment, half-life increased and drug clearance decreased linearly. Patients with moderate and severe renal impairment had a 3-fold increase in half-life and a 66% to 75% decrease in drug clearance compared to healthy subjects. Patients on hemodialysis (n=6) given a single, 25-mg dose of lenalidomide has an approximate 4.5-fold increase in half-life and an 80% decrease in drug clearance compared to healthy subjects. Approximately 40% of the administered dose was removed from the body during a single dialysis session.

In multiple myeloma patients, those patients with mild renal impairment had an AUC 56% greater than those with normal renal function.

Adjustment of the starting dose of REVLIMID is recommended in patients with moderate or severe (CLcr < 60 mL/min) renal impairment and in patients on dialysis. [see DOSAGE AND ADMINISTRATION].

Patients with Hepatic Disease: The pharmacokinetics of lenalidomide in patients with hepatic impairment have not been studied.

Age: The effects of age on the pharmacokinetics of lenalidomide have not been studied.

Pediatric: No pharmacokinetic data are available in patients below the age of 18 years.

Gender: The effects of gender on the pharmacokinetics of lenalidomide have not been studied.

Race: Pharmacokinetic differences due to race have not been studied

Clinical Studies

Multiple Myeloma

Two randomized studies (Studies 1 and 2) were conducted to evaluate the efficacy and safety of REVLIMID. These multicenter, multinational, double-blind, placebo-controlled studies compared REVLIMID plus oral pulse high-dose dexamethasone therapy to dexamethasone therapy alone in patients with multiple myeloma who had received at least one prior treatment. These studies enrolled patients with absolute neutrophil counts (ANC) ≥ 1000/mm³, platelet counts ≥ 75,000/mm³, serum creatinine ≤ 2.5 mg/dL, serum SGOT/AST or SGPT/ALT ≤ 3.0 x upper limit of normal (ULN), and serum direct bilirubin ≤ 2.0 mg/dL.

In both studies, patients in the REVLIMID/dexamethasone group took 25 mg of REVLIMID orally once daily on Days 1 to 21 and a matching placebo capsule once daily on Days 22 to 28 of each 28-day cycle. Patients in the placebo/dexamethasone group took 1 placebo capsule on Days 1 to 28 of each 28-day cycle. Patients in both treatment groups took 40 mg of dexamethasone orally once daily on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day cycle for the first 4 cycles of therapy.

The dose of dexamethasone was reduced to 40 mg orally once daily on Days 1 to 4 of each 28-day cycle after the first 4 cycles of therapy. In both studies, treatment was to continue until disease progression.

In both studies, dose adjustments were allowed based on clinical and laboratory findings. Sequential dose reductions to 15 mg daily, 10 mg daily and 5 mg daily were allowed for toxicity [see DOSAGE AND ADMINISTRATION].

Table 8 summarizes the baseline patient and disease characteristics in the two studies. In both studies, baseline demographic and disease-related characteristics were comparable between the REVLIMID/dexamethasone and placebo/dexamethasone groups.

Table 8: Baseline Demographic and Disease-Related Characteristics – Studies 1 and 2

  Study 1 Study 2
REVLIMID/Dex
N=177
Placebo/Dex
N=176
REVLIMID/Dex
N=176
Placebo/Dex
N=175
Patient Characteristics
Age (years)
  Median 64 62 63 64
  Min, Max 36, 86 37, 85 33, 84 40, 82
Sex
  Male 106 (60%) 104 (59%) 104 (59%) 103 (59%)
  Female 71 (40%) 72 (41%) 72 (41%) 72 (41%)
Race/Ethnicity
  White 141(80%) 148 (84%) 172 (98%) 175(100%)
  Other 36 (20%) 28 (16%) 4 (2%) 0 (0%)
ECOG Performance
  Status 0-1 157 (89%) 168 (95%) 150 (85%) 144 (82%)
Disease Characteristics
Multiple Myeloma Stage (Durie-Salmon)
  I 3% 3% 6% 5%
  II 32% 31% 28% 33%
  III 64% 66% 65% 63%
B2-microglobulin (mg/L)
  ≤ 2.5 mg/L 52 (29%) 51 (29%) 51 (29%) 48 (27%)
  > 2.5 mg/L 125 (71%) 125 (71%) 125 (71%) 127 (73%)
Number of Prior Therapies
  1 38% 38% 32% 33%
  ≥ 2 62% 62% 68% 67%
Types of Prior Therapies
Stem Cell Transplantation 62% 61% 55% 54%
Thalidomide 42% 46% 30% 38%
Dexamethasone 81% 71% 66% 69%
Bortezomib 11% 11% 5% 4%
Melphalan 33% 31% 56% 52%
Doxorubicin 55% 51% 56% 57%

The primary efficacy endpoint in both studies was time to progression (TTP). TTP was defined as the time from randomization to the first occurrence of progressive disease.

Preplanned interim analyses of both studies showed that the combination of REVLIMID/dexamethasone was significantly superior to dexamethasone alone for TTP. The studies were unblinded to allow patients in the placebo/dexamethasone group to receive treatment with the REVLIMID/dexamethasone combination. For both studies, the extended follow-up survival data with crossovers were analyzed. In study 1, the median survival time was 39.4 months (95%CI: 32.9, 47.4) in REVLIMID/dexamethasone group and 31.6 months (95%CI: 24.1, 40.9) in placebo/dexamethasone group, with a hazard ratio of 0.79 (95% CI: 0.61-1.03). In study 2, the median survival time was 37.5 months (95%CI: 29.9, 46.6) in REVLIMID/dexamethasone group and 30.8 months (95%CI: 23.5, 40.3) in placebo/dexamethasone group, with a hazard ratio of 0.86 (95% CI: 0.65-1.14).

Table 9: TTP Results in Study 1 and Study 2

  Study 1 Study 2
REVLIMID/Dex
N=177
Placebo/Dex
N=176
REVLIMID/Dex
N=176
Placebo/Dex
N=175
TTP
Events n (%) 73(41) 120 (68) 68 (39) 130 (74)
Median TTP in months 13.9 4.7 12.1 4.7
[95% CI] [9.5, 18.5] [3.7, 4.9] [9.5, NE] [3.8, 4.8]
Hazard Ratio [95% CI] 0.285 [0.210, 0.386] 0.324 [0.240, 0.438]
Log-rank Test p-value 3 <0.001 <0.001
Response
Complete Response (CR) n (%) 23 (13) 1 (1) 27 (15) 7 (4)
Partial Response (RR/PR) n (%) 84 (48) 33(19) 77 (44) 34 (19)
Overall Response n (%) 107 (61) 34 (19) 104 (59) 41(23)
p-value <0.001 <0.001
Odds Ratio [95% CI] 6.38 [3.95, 10.32] 4.72 [2.98, 7.49]

Figure 1 : Kaplan-Meier Estimate of Time to Progression - Study 1

Kaplan-Meier Estimate of Time to Progression - Illustration

Figure 2: Kaplan-Meier Estimate of Time to Progression - Study 2

Kaplan-Meier Estimate of Time to Progression - Illustration

Myelodysplastic Syndromes (MDS) with a Deletion 5q Cytogenetic Abnormality

The efficacy and safety of REVLIMID were evaluated in patients with transfusion-dependent anemia in low- or intermediate-1- risk MDS with a 5q (q31-33) cytogenetic abnormality in isolation or with additional cytogenetic abnormalities, at a dose of 10 mg once daily or 10 mg once daily for 21 days every 28 days in an open-label, single-arm, multi-center study. The major study was not designed nor powered to prospectively compare the efficacy of the 2 dosing regimens. Sequential dose reductions to 5 mg daily and 5 mg every other day, as well as dose delays, were allowed for toxicity [Dosage and Administration (2.2)].

This major study enrolled 148 patients who had RBC transfusion dependent anemia. RBC transfusion dependence was defined as having received ≥ 2 units of RBCs within 8 weeks prior to study treatment. The study enrolled patients with absolute neutrophil counts (ANC) ≥ 500/mm³, platelet counts ≥ 50,000/mm³, serum creatinine ≤ 2.5 mg/dL, serum SGOT/AST or SGPT/ALT ≤ 3.0 x upper limit of normal (ULN), and serum direct bilirubin ≤ 2.0 mg/dL. Granulocyte colony-stimulating factor was permitted for patients who developed neutropenia or fever in association with neutropenia. Baseline patient and disease-related characteristics are summarized in Table 10.

Table 10: Baseline Demographic and Disease-Related Characteristics in the MDS Study

  Overall (N=148)
Age (years)
  Median 71.0
  Min, Max 37.0, 95.0
Gender n (%)
  Male 51 (34.5)
  Female 97 (65.5)
Race n (%)
  White 143 (96.6)
  Other 5 (3.4)
Duration of MDS (years)
  Median 2.5
  Min, Max 0.1, 20.7
Del 5 (q31-33) Cytogenetic Abnormality n (%)
  Yes 148 (100.0)
  Other cytogenetic abnormalities 37 (25.2)
IPSS Scorea n (%)
  Low (0) 55 (37.2)
  Intermediate-1 (0.5-1.0) 65 (43.9)
  Intermediate-2 (1.5-2.0) 6 (4.1)
  High (≥ 2.5) 2 (1.4)
  Missing 20 (13.5)
FAB Classificationb from central review n (%)
  RA 77 (52.0)
  RARS 16 (10.8)
  RAEB 30 (20.3)
  CMML 3 (2.0)
aIPSS Risk Category: Low (combined score = 0), Intermediate-1 (combined score = 0.5 to 1.0),Intermediate-2 (combined score = 1.5 to 2.0), High (combined score ≥ 2.5); Combined score = (Marrow blast score + Karyotype score + Cytopenia score)
b French-American-British (FAB) classification of MDS.

The frequency of RBC transfusion independence was assessed using criteria modified from the International Working Group (IWG) response criteria for MDS. RBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive “rolling” 56 days (8 weeks) during the treatment period.

Transfusion independence was seen in 99/148 (67%) patients (95% CI [59, 74]). The median duration from the date when RBC transfusion independence was first declared (i.e., the last day of the 56-day RBC transfusion-free period) to the date when an additional transfusion was received after the 56-day transfusion-free period among the 99 responders was 44 weeks (range of 0 to >67 weeks). Ninety percent of patients who achieved a transfusion benefit did so by completion of three months in the study.

RBC transfusion independence rates were unaffected by age or gender.

The dose of REVLIMID was reduced or interrupted at least once due to an adverse event in 118 (79.7%) of the 148 patients; the median time to the first dose reduction or interruption was 21 days (mean, 35.1 days; range, 2-253 days), and the median duration of the first dose interruption was 22 days (mean, 28.5 days; range, 2-265 days). A second dose reduction or interruption due to adverse events was required in 50 (33.8%) of the 148 patients. The median interval between the first and second dose reduction or interruption was 51 days (mean, 59.7 days; range, 15-205 days) and the median duration of the second dose interruption was 21 days (mean, 26 days; range, 2-148 days).

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

MEDICATION GUIDE

REVLIMID®
(rev-li-mid)
(lenalidomide) Capsules

Read the Medication Guide that comes with REVLIMID before you start taking it and each time you get a new prescription. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

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 RevAssist® program.
  • 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 (THALOMID). We know thalidomide can cause severe life- threatening birth defects. REVLIMID has not been tested in pregnant women. REVLIMID has harmed unborn animals in animal testing.
    Females must not get pregnant:
    • for 4 weeks before starting REVLIMID
    • while taking REVLIMID
    • during any breaks (interruptions) in your treatment with REVLIMID
    • for 4 weeks after stopping REVLIMID
      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 1-888-668-2528 for medical information. Healthcare providers and patients should report all cases of pregnancy to:
    • FDA MedWatch at 1-800-FDA-1088, and
    • Celgene Corporation at 1-888-423-5436
      It is known that REVLIMID passes into semen, so:
    • Males, including those who have had a vasectomy,must use a latex 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 4 weeks after stopping REVLIMID. (If you or your partner are allergic to latex, please consult with your healthcare provider)
    • 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.
    • Do not donate sperm while taking REVLIMID, during any breaks (interruptions) in your treatment, and for 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 patients. You may need a blood transfusion or certain medicines if your blood counts drop too low. If you are being treated for del 5q myelodysplastic syndromes (MDS) your blood counts should be checked weekly during the first 8 weeks of treatment with REVLIMID, and at least monthly thereafter. If you are being treated for multiple myeloma, your blood counts should be checked every 2 weeks for the first 12 weeks and then at least monthly thereafter.
      A higher chance for blood clots in your veins and lungs. Call your healthcare provider or get medical help right away if you get any of these signs or symptoms:
    • shortness of breath
    • chest pain
    • arm or leg swelling

What is REVLIMID?

REVLIMID is a prescription medicine taken by mouth to treat certain patients who have myelodysplastic syndromes (MDS). People with MDS have bone marrow that does not produce enough mature blood cells. This causes a lack of healthy blood cells that can function properly in the body. There are different types of MDS. REVLIMID is for the type of MDS with a chromosome problem where part of chromosome 5 is missing. This type of MDS is known as deletion 5q MDS. People with this type of MDS may have low red blood cell counts that require treatment with blood transfusions.

REVLIMID is also used with dexamethasone to treat people with multiple myeloma who have already had another treatment. Multiple myeloma is a cancer of plasma cells. Plasma cells are found in the bone marrow. Normal plasma cells produce proteins called antibodies. Some antibodies can attack and kill disease causing germs. People with multiple myeloma may have low blood cell counts and immune problems giving them a higher chance for getting infections such as pneumonia. They may also have bone pain and breaks (fractures).

Who should not take REVLIMID?

  • Do not take REVLIMID if you are pregnant, plan to become pregnant, or become pregnant during REVLIMID treatment. See “What is the most important information I should know about REVLIMID?”
  • Do not take REVLIMID if you are allergic to anythingin it. See the end of this Medication Guide for a complete list of ingredients in REVLIMID.

What should I tell my healthcare provider before taking REVLIMID?

Tell your healthcare provider about all of your medical conditions, including if you:

  • are pregnant or breastfeeding. REVLIMID must not be used by women who are pregnant or breastfeeding. See “What is the most important information I should know about REVLIMID?” It is not known if REVLIMID passes into your breast milk and harms your baby.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. REVLIMID and other medicines may affect each other causing serious side effects. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist.

How should I take REVLIMID?

Take REVLIMID exactly as prescribed and follow all the instructions of the RevAssist program.

Before prescribing REVLIMID, your healthcare provider will:

    • explain the RevAssist program to you
    • have you sign the Patient-Physician Agreement Form
  • Swallow REVLIMID capsules whole with water once a day. Do not break, chew, or open your capsules.
  • Do not open the REVLIMID capsules or handle them any more than needed. If you touch a broken REVLIMID capsule or the medicine in the capsule, wash the area of your body with soap and water.
  • If you miss a dose of REVLIMID, and it has been less than 12 hours since your regular time, take it as soon as you remember. If it has been more than 12 hours, just skip your missed dose. Do not take 2 doses at the same time.
  • If you take too much REVLIMID or overdose, call your healthcare provider or poison control center right away.

Females who can become pregnant:

  • 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.
    If you miss your period or have unusual bleeding, you will need to have a pregnancy test and receive counseling.
  • must agree to use 2 different forms of effective birth control at the same time, for 4 weeks before, while taking, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping REVLIMID.

Males who take REVLIMID, even those who have had a vasectomy, must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant. (If you or your partner is allergic to latex, please consult with your healthcare provider.)

What should I avoid while taking REVLIMID?

  • Females: Do not get pregnant and do not breastfeed while taking REVLIMID.
    Males: Do not donate sperm, See “What is the most important information I should I know about REVLIMID?”, “Who should not take REVLIMID?”, and “What should I avoid while taking REVLIMID?”.
  • Do not share REVLIMID with other people. It may cause birth defects and other serious problems.
  • Do not donate blood while you take REVLIMID, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping REVLIMID. If someonewho is pregnant gets your donated blood, her baby may be exposed to REVLIMID and may be born with birth defects.

What are the possible side effects of REVLIMID?

  • REVLIMID may cause serious side effects.
  • See “What is the most important information I should know about REVLIMID?”
  • Serious skin reactions. Serious skin reactions can happen with REVLIMID and may cause death. Call your healthcare provider right away if you have any skin reaction while taking REVLIMID.
  • Tumor lysis syndrome. Metabolic complications that can occur during treatment of cancer and sometimes even without treatment. These complications are caused by the breakdown products of dying cancer cells and may include the following: changes to blood chemistry, high potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heart beat, seizures, and sometimes death.

Common side effects of REVLIMID are:

These are not all the possible side effects of REVLIMID. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store REVLIMID?

  • Store REVLIMID at room temperature, 59°F to 86°F (15°C to 30°C).

Keep REVLIMID and all medicines out of the reach of children.

General information about REVLIMID

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take REVLIMID for conditions for which it was not prescribed. Do not give REVLIMID to other people, even if they have the same symptoms you have. It may harm them and may cause birth defects.

This Medication Guide provides a summary of the most important information about REVLIMID. If you would like more information, talk with your healthcare provider.You can ask your healthcare provider or pharmacist for information about REVLIMID that is written for healthcare professionals. You can also call 1-888-423-5436 or visit www.REVLIMID.com.

What are the ingredients in REVLIMID?

Active ingredient: lenalidomide

Inactive ingredients: lactose anhydrous, microcrystallinecellulose, croscarmellose sodium, and magnesium stearate.

The 5 mg and 25 mg capsule shells contain gelatin, titanium dioxide and black ink. The 10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink. The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide and black ink.

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

MEDICATION GUIDE

REVLIMID®
(rev-li-mid)
(lenalidomide) Capsules

Read the Medication Guide that comes with REVLIMID before you start taking it and each time you get a new prescription. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or your treatment.

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 RevAssist® program.
  • 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 (THALOMID). We know thalidomide can cause severe life- threatening birth defects. REVLIMID has not been tested in pregnant women. REVLIMID has harmed unborn animals in animal testing.
    Females must not get pregnant:
    • for 4 weeks before starting REVLIMID
    • while taking REVLIMID
    • during any breaks (interruptions) in your treatment with REVLIMID
    • for 4 weeks after stopping REVLIMID
      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 1-888-668-2528 for medical information. Healthcare providers and patients should report all cases of pregnancy to:
    • FDA MedWatch at 1-800-FDA-1088, and
    • Celgene Corporation at 1-888-423-5436
      It is known that REVLIMID passes into semen, so:
    • Males, including those who have had a vasectomy,must use a latex 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 4 weeks after stopping REVLIMID. (If you or your partner are allergic to latex, please consult with your healthcare provider)
    • 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.
    • Do not donate sperm while taking REVLIMID, during any breaks (interruptions) in your treatment, and for 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 patients. You may need a blood transfusion or certain medicines if your blood counts drop too low. If you are being treated for del 5q myelodysplastic syndromes (MDS) your blood counts should be checked weekly during the first 8 weeks of treatment with REVLIMID, and at least monthly thereafter. If you are being treated for multiple myeloma, your blood counts should be checked every 2 weeks for the first 12 weeks and then at least monthly thereafter.
      A higher chance for blood clots in your veins and lungs. Call your healthcare provider or get medical help right away if you get any of these signs or symptoms:
    • shortness of breath
    • chest pain
    • arm or leg swelling

What is REVLIMID?

REVLIMID is a prescription medicine taken by mouth to treat certain patients who have myelodysplastic syndromes (MDS). People with MDS have bone marrow that does not produce enough mature blood cells. This causes a lack of healthy blood cells that can function properly in the body. There are different types of MDS. REVLIMID is for the type of MDS with a chromosome problem where part of chromosome 5 is missing. This type of MDS is known as deletion 5q MDS. People with this type of MDS may have low red blood cell counts that require treatment with blood transfusions.

REVLIMID is also used with dexamethasone to treat people with multiple myeloma who have already had another treatment. Multiple myeloma is a cancer of plasma cells. Plasma cells are found in the bone marrow. Normal plasma cells produce proteins called antibodies. Some antibodies can attack and kill disease causing germs. People with multiple myeloma may have low blood cell counts and immune problems giving them a higher chance for getting infections such as pneumonia. They may also have bone pain and breaks (fractures).

Who should not take REVLIMID?

  • Do not take REVLIMID if you are pregnant, plan to become pregnant, or become pregnant during REVLIMID treatment. See “What is the most important information I should know about REVLIMID?”
  • Do not take REVLIMID if you are allergic to anythingin it. See the end of this Medication Guide for a complete list of ingredients in REVLIMID.

What should I tell my healthcare provider before taking REVLIMID?

Tell your healthcare provider about all of your medical conditions, including if you:

  • are pregnant or breastfeeding. REVLIMID must not be used by women who are pregnant or breastfeeding. See “What is the most important information I should know about REVLIMID?” It is not known if REVLIMID passes into your breast milk and harms your baby.

Tell your healthcare provider about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. REVLIMID and other medicines may affect each other causing serious side effects. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist.

How should I take REVLIMID?

Take REVLIMID exactly as prescribed and follow all the instructions of the RevAssist program.

Before prescribing REVLIMID, your healthcare provider will:

    • explain the RevAssist program to you
    • have you sign the Patient-Physician Agreement Form
  • Swallow REVLIMID capsules whole with water once a day. Do not break, chew, or open your capsules.
  • Do not open the REVLIMID capsules or handle them any more than needed. If you touch a broken REVLIMID capsule or the medicine in the capsule, wash the area of your body with soap and water.
  • If you miss a dose of REVLIMID, and it has been less than 12 hours since your regular time, take it as soon as you remember. If it has been more than 12 hours, just skip your missed dose. Do not take 2 doses at the same time.
  • If you take too much REVLIMID or overdose, call your healthcare provider or poison control center right away.

Females who can become pregnant:

  • 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.
    If you miss your period or have unusual bleeding, you will need to have a pregnancy test and receive counseling.
  • must agree to use 2 different forms of effective birth control at the same time, for 4 weeks before, while taking, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping REVLIMID.

Males who take REVLIMID, even those who have had a vasectomy, must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant. (If you or your partner is allergic to latex, please consult with your healthcare provider.)

What should I avoid while taking REVLIMID?

  • Females: Do not get pregnant and do not breastfeed while taking REVLIMID.
    Males: Do not donate sperm, See “What is the most important information I should I know about REVLIMID?”, “Who should not take REVLIMID?”, and “What should I avoid while taking REVLIMID?”.
  • Do not share REVLIMID with other people. It may cause birth defects and other serious problems.
  • Do not donate blood while you take REVLIMID, during any breaks (interruptions) in your treatment, and for 4 weeks after stopping REVLIMID. If someonewho is pregnant gets your donated blood, her baby may be exposed to REVLIMID and may be born with birth defects.

What are the possible side effects of REVLIMID?

  • REVLIMID may cause serious side effects.
  • See “What is the most important information I should know about REVLIMID?”
  • Serious skin reactions. Serious skin reactions can happen with REVLIMID and may cause death. Call your healthcare provider right away if you have any skin reaction while taking REVLIMID.
  • Tumor lysis syndrome. Metabolic complications that can occur during treatment of cancer and sometimes even without treatment. These complications are caused by the breakdown products of dying cancer cells and may include the following: changes to blood chemistry, high potassium, phosphorus, uric acid, and low calcium consequently leading to changes in kidney function, heart beat, seizures, and sometimes death.

Common side effects of REVLIMID are:

These are not all the possible side effects of REVLIMID. Tell your healthcare provider about any side effect that bothers you or that does not go away.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store REVLIMID?

  • Store REVLIMID at room temperature, 59°F to 86°F (15°C to 30°C).

Keep REVLIMID and all medicines out of the reach of children.

General information about REVLIMID

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not take REVLIMID for conditions for which it was not prescribed. Do not give REVLIMID to other people, even if they have the same symptoms you have. It may harm them and may cause birth defects.

This Medication Guide provides a summary of the most important information about REVLIMID. If you would like more information, talk with your healthcare provider.You can ask your healthcare provider or pharmacist for information about REVLIMID that is written for healthcare professionals. You can also call 1-888-423-5436 or visit www.REVLIMID.com.

What are the ingredients in REVLIMID?

Active ingredient: lenalidomide

Inactive ingredients: lactose anhydrous, microcrystallinecellulose, croscarmellose sodium, and magnesium stearate.

The 5 mg and 25 mg capsule shells contain gelatin, titanium dioxide and black ink. The 10 mg capsule shell contains gelatin, FD&C blue #2, yellow iron oxide, titanium dioxide and black ink. The 15 mg capsule shell contains gelatin, FD&C blue #2, titanium dioxide and black ink.

Last reviewed on RxList: 5/21/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Revlimid Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

LENALIDOMIDE - ORAL

(len-a-LID-o-mide)

WARNING: Lenalidomide is a drug that is very similar to thalidomide, which is known to cause severe birth defects or death in unborn babies. If lenalidomide is taken during pregnancy, it may also cause severe birth defects or death in unborn babies. Therefore, this drug must never be used during pregnancy nor by women who could become pregnant while using this drug. Pregnancy must be ruled out before starting lenalidomide. Women must have two negative pregnancy tests before starting lenalidomide, the first 10-14 days before the first dose and the second within 24 hours before the first dose. Women must work with their doctors to check for and prevent pregnancy while using this medication. (See also Notes section.)

For patients to receive this medication, all doctors, pharmacists, and patients must agree to, understand, and carefully follow the requirements of the Revlimid Education and Prescribing Safety Program, also known as the RevAssist program, developed by the U.S. Food and Drug Administration.

If the patient taking lenalidomide is between the ages 12-18, then a parent or legal guardian must also read the educational material and agree to carefully follow the requirements of the RevAssist program.

Patients (male and female) who use this medication must use two reliable forms of birth control. For males, this means using a latex condom along with other effective birth control used by the female partner. If pregnancy does occur during treatment, stop this medication and contact your doctor immediately. (See also Precautions section.)

Lenalidomide may benefit you by helping increase the number of functioning red blood cells. Unfortunately, it may also increase your risk of developing serious bone marrow problems such as low white blood cell counts or low platelet counts. Seek immediate medical attention if you develop the following symptoms: persistent fever, persistent sore throat, easy bleeding/bruising. Most patients will experience these effects, which will require your doctor to stop and restart lenalidomide or decrease your dose.

Lenalidomide can cause serious (sometimes fatal) blood clots in veins and lungs. Seek immediate medical attention if you develop the following symptoms: calf pain/swelling, chest pain, trouble breathing.

USES: This medication is used to treat anemia in patients with certain blood/bone marrow disorders (myelodysplastic syndromes-MDS). These patients do not have enough properly working red blood cells. They often require blood transfusions to reverse their anemia. Lenalidomide may decrease the need for treatment with blood transfusions. This medication may also be used to treat a certain type of cancer (multiple myeloma).

Lenalidomide is a type of drug known as an immunomodulator. It is believed to work by decreasing the immune system's response, thereby lowering the number of working red blood cells that are destroyed naturally by the body.

HOW TO USE: This medication must be used only within the RevAssist guidelines in order to avoid any possible exposure of an unborn baby to the drug. Consult your doctor or pharmacist.

Read the Medication Guide provided by your pharmacist before you start using lenalidomide and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Before starting therapy, women of childbearing age should have two negative pregnancy tests before taking the drug. (See Warning section.)

Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow this medication whole with water. Dosage is based on your medical condition, response to therapy, and laboratory test results. Be sure to follow your doctor's directions carefully.

Do not open, chew, or break the capsules, or handle them any more than needed. If any of the powder from the capsule gets on your skin, wash the area with soap and water.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from broken capsules. All people should wash their hands thoroughly after handling this drug.

Use this medication regularly in order to get the most benefit from it. Remember to take it at the same time each day.

Inform your doctor if your condition persists or worsens.

Disclaimer

Revlimid Consumer (continued)

SIDE EFFECTS: See also Warning section.

Diarrhea, tiredness, dizziness, dry skin, constipation, stomach pain, vomiting, dry mouth, unpleasant taste, loss of appetite, headache, trouble sleeping, or painful urination may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes, pounding heartbeat.

People with multiple myeloma who are treated with this medication may rarely get other cancers (such as acute leukemia, tumors). Consult your doctor for more details.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Revlimid (lenalidomide) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking lenalidomide, tell your doctor or pharmacist if you are allergic to it; or to thalidomide; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.

This drug may make you dizzy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at a greater risk for side effects while using lenalidomide.

Because lenalidomide can cause severe birth defects or death to an unborn baby, several precautions are noted below.

Do not donate blood while using lenalidomide and for 4 weeks after stopping this drug.

Males - This medication passes into semen. Therefore, always use a latex condom when having sexual intercourse with a woman of childbearing age, even if you have had a vasectomy. You must not donate sperm while using lenalidomide and for 4 weeks after stopping this drug.

Use two forms of effective birth control together for at least 4 weeks before beginning lenalidomide treatment, during lenalidomide treatment, and for 4 weeks after stopping lenalidomide, or avoid intercourse completely during this period. Reliable birth control is necessary even if you have been unable to get pregnant in the past. Consult your doctor for more information about the right forms of birth control to use during this therapy.

Immediately tell your doctor if your period is late or if you have abnormal vaginal (menstrual) bleeding.

Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from broken capsules.

Lenalidomide must not be used during pregnancy. If you become pregnant or think you may be pregnant, inform your doctor immediately. Even a single dose of lenalidomide taken during pregnancy can cause severe birth defects. If pregnancy does occur during treatment, this drug must be stopped immediately.

It is not known whether this drug passes into breast milk. Because of the potential for serious reactions in nursing infants, breast-feeding is not recommended while using lenalidomide.

Disclaimer

Revlimid Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., complete blood counts, kidney function) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

If you are a woman with regular periods, test for pregnancy before treatment, weekly during the first 4 weeks of treatment, then every 4 weeks thereafter. If you have irregular periods, test every 2 weeks.

MISSED DOSE: If you miss a dose, take it as soon as you remember if it is less than 12 hours after the time you would usually take it. If more than 12 hours have passed, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised May 2012. Copyright(c) 2012 First Databank, Inc.

Revlimid Patient Information Including Side Effects

Brand Names: Revlimid

Generic Name: lenalidomide (Pronunciation: LEN a LID o mide)

What is lenalidomide (Revlimid)?

Lenalidomide affects the immune system. It helps promote immune responses to prevent inflammation in the body.

Lenalidomide treats anemia (a lack of red blood cells in the body) and multiple myeloma (cancer resulting from a progressive blood disease). It is used in patients with myelodysplastic syndrome caused by an abnormal chromosome. This disorder is also called deletion 5q MDS, because part of chromosome 5 is missing. In people with this disorder, the bone marrow does not produce enough healthy blood cells.

Lenalidomide may also be used for other purposes not listed in this medication guide.

What are the possible side effects of lenalidomide (Revlimid)?

Stop using lenalidomide and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • chest pain, sudden shortness of breath, coughing up blood;
  • pain or swelling in your arm, thigh, or calf;
  • easy bruising, unusual bleeding or weakness;
  • fever, chills, body aches, flu symptoms;
  • lower back pain, blood in your urine;
  • urinating less than usual or not at all;
  • numbness or tingly feeling around your mouth;
  • muscle weakness, tightness, or contraction, overactive reflexes;
  • fast or slow heart rate, weak pulse, feeling short of breath, confusion, fainting;
  • severe blistering, peeling, and red skin rash; or
  • the first sign of any skin rash, no matter how mild.

Less serious side effects may include:

  • nausea, diarrhea, constipation;
  • dry or itchy skin;
  • runny or stuffy nose;
  • muscle or joint pain;
  • headache; or
  • tiredness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Revlimid (lenalidomide) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about lenalidomide (Revlimid)?

For Women: You will be required to use two reliable forms of birth control beginning 4 weeks before you start taking lenalidomide and ending 4 weeks after you stop taking it. Any woman who has not had a hysterectomy or has not been in menopause for at least 24 months in a row must agree in writing to use birth control before, during, and after taking lenalidomide. Even women with fertility problems are required to use birth control while taking this medication. You must also have a negative pregnancy test at 10 to 14 days before treatment and again at 24 hours before. While you are taking lenalidomide, you will have a pregnancy test every 4 weeks.

Stop using lenalidomide and call your doctor at once if you quit using birth control, if your period is late, or if you think you might be pregnant.

For Men: You must not cause a woman to become pregnant while you are taking lenalidomide because the medicine may affect your sperm and cause birth defects in the baby. You must agree in writing to always use latex condoms when having sex with a woman who is able to get pregnant, even if you have had a vasectomy.

Lenalidomide is available only under a special program called RevAssist. You must be registered in the program and sign documents stating that you understand the dangers of this medication and that you agree to use birth control measures as required by the program.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Never give lenalidomide to another person, even if he or she has the same disorder for which you are being treated.

Do not donate blood or sperm while you are using lenalidomide.

Side Effects Centers

Revlimid Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking lenalidomide (Revlimid)?

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before taking lenalidomide, tell your doctor if you have:

  • kidney disease; or
  • a history of blood clots or stroke.

It is not known if lenalidomide passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

For Women: If you have not had a hysterectomy or have not been in menopause for at least 24 months in a row, you will be required to use two forms of birth control beginning 4 weeks before you start taking lenalidomide and ending 4 weeks after you stop taking it. Even women with fertility problems are required to use birth control while taking this medication. You must also have a negative pregnancy test at 10 to 14 days before treatment and again at 24 hours before. While you are taking lenalidomide, you will have a pregnancy test every 4 weeks.

The birth control method you use must be proven highly effective, such as birth control pills, an intrauterine device (IUD), a tubal ligation, or a sexual partner's vasectomy. The extra form of birth control you use must be a barrier method such as a latex condom, a diaphragm, or a cervical cap.

Stop using lenalidomide and call your doctor at once if you quit using birth control, if your period is late, or if you think you might be pregnant.

For Men: You must not cause a woman to become pregnant while you are taking lenalidomide because the medicine may affect your sperm and cause birth defects in the baby. You must agree in writing to always use latex condoms when having sex with a woman who is able to get pregnant, even if you have had a vasectomy. Contact your doctor if you have had unprotected sex, even once, or if you think your female sexual partner may be pregnant.

Lenalidomide is available only under a special program called RevAssist. Under this program, only registered doctors and pharmacists can prescribe and dispense lenalidomide. You must be registered in the program and sign documents stating that you understand the dangers of this medication and that you agree to use birth control measures as required by the program.

For patients between 12 and 18 years, a parent or legal guardian must read all written requirements for the RevAssist program and sign the agreements on behalf of the patient.

How should I take lenalidomide (Revlimid)?

While you are using lenalidomide, you will be required to be listed on a patient registry and participate in occasional telephone surveys. You will be limited to a 28-day supply of lenalidomide each time your prescription is refilled. You may continue getting refills only if you participate fully in the RevAssist program and commit to all agreements.

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Never give lenalidomide to another person, even if he or she has the same disorder for which you are being treated.

Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take each dose with a full glass of water.

Swallow the capsule whole, without breaking it open.

To be sure lenalidomide is helping your condition and not causing harmful effects, your blood will need to be tested every week for the first two months of treatment, and then every month after that. Do not miss any visits to your doctor.

Store lenalidomide at room temperature away from moisture and heat.

Side Effects Centers

Revlimid Patient Information including If I Miss a Dose

What happens if I miss a dose (Revlimid)?

Take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Revlimid)?

Seek emergency medical attention if you think you have used too much of this medicine.

An overdose of lenalidomide is not expected to produce life-threatening symptoms.

What should I avoid while taking lenalidomide (Revlimid)?

Do not donate blood or sperm while you are using lenalidomide.

What other drugs will affect lenalidomide (Revlimid)?

There may be other drugs that can affect lenalidomide. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about lenalidomide.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 3.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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Side Effects Centers

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