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WARNINGS and Adverse Events
Hematologic adverse events
Grade 3/4 neutropenia occurred in 21% of REVLIMID®(lenalidomide) + dex patients vs 3% of placebo + dex patients; 2% of REVLIMID® + dex patients had febrile neutropenia vs 0% of placebo + dex patients.
Grade 3/4 thrombocytopenia occurred in 10% of REVLIMID® + dex patients vs 6% of placebo + dex patients.
Grade 3/4 anemia occurred in 8% of REVLIMID® + dex patients vs 4% of placebo + dex patients.
Incidence of thrombotic events
The overall incidence of thrombotic events-including DVT, pulmonary embolism (PE), thrombosis, and thromboembolism-was higher among patients taking REVLIMID® + dex (12%; 43/346) vs placebo + dex (4%; 14/345).
Grade 3/4 DVT was significantly more frequent with REVLIMID® + dex (7%) vs placebo + dex (3%).
Grade 3/4 PE was not significantly different with REVLIMID® + dex (3%) vs placebo + dex (1%).
Prophylactic anticoagulation was not used in these 2 studies.
No significant difference between treatment arms in grade 3/4 constipation, fatigue, or neuropathy
There was no significant difference between treatment arms in neuropathy (REVLIMID® + dex, 2%; placebo + dex, 0.6%, P=NS).
Clinically relevant adverse events or those occurring in >10% of patients with multiple myeloma
REVLIMID® + dex (n=346)
Placebo + dex (n=345)
Hematologic
All grades
Grade 3/4
All grades
Grade 3/4
Neutropenia
28%*
21%*
5%
3%
Anemia NOS
24%*
8%*
17%
4%
Thrombocytopenia
17%*
10%*
10%
6%
Leukopenia NOS
__†
4%*
__†
<1%
Lymphopenia
__†
2%
__†
1%
Nonhematologic
All grades
Grade 3/4
All grades
Grade 3/4
Constipation
39%*
2%
19%
<1%
Fatigue
38%
6%
37%
4%
Insomnia
32%
__‡
37%
__‡
Muscle cramp
30%
__‡
21%
__‡
Diarrhea NOS
29%
2%
25%
1%
Asthenia
23%
4%
25%
5%
Pyrexia
23%
1%
19%
2%
Nausea
22%
__‡
19%
__‡
Headache
21%
__‡
21%
__‡
Edema peripheral
21%
__‡
19%
__‡
Dizziness
21%
__‡
15%
__‡
Dyspnea
20%
3%
15%
2%
Tremor
20%*
__‡
7%
__‡
Weight decreased
18%
__‡
14%
__‡
Rash NOS
16%*
__‡
8%
__‡
Back pain
15%
__‡
14%
__‡
Hyperglycemia NOS
15%
8%
14%
8%
Muscle weakness NOS
15%
5%
15%
3%
Vision blurred
15%
__‡
10%
__‡
Cough
15%
__‡
21%
__‡
Dyspepsia
14%
__‡
13%
__‡
Upper respiratory tract infections NOS
14%
__‡
13%
__‡
Anorexia
14%
__‡
9%
__‡
Dysgeusia
13%
__‡
9%
__‡
Parasthesia
12%
__‡
13%
__‡
Pneumonia NOS
11%
6%
8%
5%
Hypokalemia
11%
3%
5%
1%
Vomiting NOS
10%
__‡
8%
__‡
Arthralgia
10%
__‡
15%
__‡
Pooled analysis from Studies 1 and 2.
NOS=not otherwise specified.
*More frequent with REVLIMID® + dex than with placebo + dex. †Occurred in <10% of patients. ‡Occurred in <2% of patients.
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 Table 7 in the Prescribing Information. Patients on therapy 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.
REVLIMID® (lenalidomide) in combination with dexamethasone is indicated for the treatment of multiple myeloma patients who have received at least one prior therapy.
REVLIMID® (lenalidomide) is indicated for 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.
Important Safety Information
WARNINGS:
1. POTENTIAL FOR HUMAN BIRTH DEFECTS.
Lenalidomide is an analogue of thalidomide. Thalidomide is a known human teratogen
that causes severe life-threatening human birth defects. If lenalidomide is taken
during pregnancy, it may cause birth defects or death to an unborn baby. Females
should be advised to avoid pregnancy while taking REVLIMID®
(lenalidomide).
Special Prescribing Requirements
Because of this potential toxicity and to avoid fetal
exposure to REVLIMID® (lenalidomide),
REVLIMID® (lenalidomide) is only
available under a special restricted distribution program. This program is called
“RevAssist®”. Under this program,
only prescribers and pharmacists registered with the program can prescribe and dispense
the product. In addition, REVLIMID®
(lenalidomide) must only be dispensed to patients who are registered and meet all
the conditions of the RevAssist® program.
2. HEMATOLOGIC TOXICITY (NEUTROPENIA AND THROMBOCYTOPENIA).
This drug is associated with significant neutropenia and thrombocytopenia. Eighty
percent of patients with del 5q myelodysplastic syndromes had to have a dose delay/reduction
during the major study. Thirty-four percent of patients had to have a second dose
delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled
in the study. Patients on therapy for del 5q myelodysplastic syndromes 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)
3. DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM.
This drug has demonstrated a significantly increased risk of deep venous thrombosis
(DVT) and pulmonary embolism (PE) in patients with multiple myeloma who were treated
with REVLIMID® (lenalidomide)
combination therapy. Patients and physicians are advised to be observant for the
signs and symptoms of thromboembolism. Patients should be instructed to seek medical
care if they develop symptoms such as shortness of breath, chest pain, or arm or
leg swelling. It is not known whether prophylactic anticoagulation or antiplatelet
therapy prescribed in conjunction with REVLIMID®
(lenalidomide) may lessen the potential for venous thromboembolic events. The decision
to take prophylactic measures should be done carefully after an assessment of an
individual patient’s underlying risk factors.
You can get the information about REVLIMID®
(lenalidomide) and the RevAssist®
program on the Internet at www.REVLIMID.com or by calling the manufacturer's
toll-free number at
1-888-423-5436.
In the pooled multiple myeloma studies, Grade 3 and 4 hematologic toxicities were more frequent in patients treated with the combination of REVLIMID® (lenalidomide) and dexamethasone than in patients treated with dexamethasone alone
Patients on therapy 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
CONTRAINDICATIONS: Hypersensitivity:
REVLIMID®(lenalidomide) is contraindicated in any patients who have demonstrated hypersensitivity to the drug or its components
PRECAUTIONS: Renal impairment:
Since lenalidomide is primarily excreted unchanged by the kidney, adjustments to the starting dose of REVLIMID® (lenalidomide) are recommended to provide appropriate drug exposure in patients with moderate or severe (CLcr < 60 mL/min) renal impairment and in patients on dialysis
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it would be prudent to monitor renal function
Nursing mothers:
It is not known whether REVLIMID® (lenalidomide) is excreted in human milk
Because of the potential for adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother
ADVERSE REACTIONS: Multiple Myeloma
In the REVLIMID® (lenalidomide)/dexamethasone treatment group, 151 patients (45%) underwent at least one dose interruption with or without a dose reduction of REVLIMID® (lenalidomide) compared to 21% in the placebo/dexamethasone treatment group
Of these patients who had one dose interruption with or without a dose reduction, 50% in the REVLIMID® (lenalidomide)/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 MM patients who received the combination of REVLIMID® (lenalidomide)/dexamethasone compared to placebo/dexamethasone
Other adverse events reported in multiple myeloma patients (REVLIMID® (lenalidomide)/dexamethasone vs dexamethasone/placebo): constipation (39% vs 19%), fatigue (38% vs 37%), insomnia (32% vs 37%), muscle cramp (30% vs 21%), diarrhea (29% vs 25%), neutropenia (28% vs 5%), anemia (24% vs 17%), asthenia (23% vs 25%), pyrexia (23% vs 19%), nausea (22% vs 19%), headache (21% vs 21%), peripheral edema (21% vs 19%), dizziness (21% vs 15%), dyspnea (20% vs 15%), tremor (20% vs 7%), decreased weight (18% vs 14%), thrombocytopenia (17% vs 10%), rash (16% vs 8%), back pain (15% vs 14%), hyperglycemia (15% vs 14%), and muscle weakness (15% vs 15%).
Myelodysplastic Syndromes
Thrombocytopenia (61.5%; 91/148) and neutropenia (58.8%; 87/148) were the most frequently reported adverse events observed in the del 5q MDS population
Other adverse reactions reported in del 5q MDS patients (REVLIMID® (lenalidomide)): diarrhea (49%), pruritus (42%), rash (36%), fatigue (31%), constipation (24%), nausea (24%), nasopharyngitis (23%), arthralgia (22%), pyrexia (21%), back pain (21%), peripheral edema (20%), cough (20%), dizziness (20%), headache (20%), muscle cramp (18%), dyspnea (17%), and pharyngitis (16%).
DOSAGE AND ADMINISTRATION:
Dosing is continued or modified based upon clinical and laboratory findings. Dosing modifications are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade 3 or 4 toxicity judged to be related to REVLIMID® (lenalidomide)
For other Grade 3 or 4 toxicities judged to be related to REVLIMID® (lenalidomide), hold treatment and restart at next lower dose level when toxicity has resolved to less than or equal to Grade 2
Please see full Prescribing Information, including Boxed WARNINGS, CONTRAINDICATIONS, PRECAUTIONS, and ADVERSE REACTIONS.
