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REVLIMID® (lenalidomide) capsules for the treatment of multiple myeloma

Well-established safety profile in maintenance therapy trials1

The frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then decreased over time or remained stable throughout treatment

  • The most frequently reported adverse reactions (more than 20% in the REVLIMID arm) across both studies were neutropenia, thrombocytopenia, leukopenia, anemia, upper respiratory tract infection, bronchitis, nasopharyngitis, cough, gastroenteritis, diarrhea, rash, fatigue, asthenia, muscle spasm, and pyrexia
  • The most frequently reported Grade 3 or 4 adverse reactions (more than 20% in the REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia
  • In the MM maintenance therapy trials, Grade 3 or 4 neutropenia was reported in up to 59% of REVLIMID-treated patients and Grade 3 or 4 thrombocytopenia in up to 38% of REVLIMID-treated patients
  • VTE and ATE are increased in patients treated with REVLIMID
    • Prophylactic medications (aspirin, heparin, or warfarin) could be prescribed for patients at high risk for thrombosis in Study 19
    • Protocol did not include systematic thromboprophylaxis in Study 29
  • The serious adverse reactions lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm

Important Safety Information About Second Primary Malignancies (SPM)

  • Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment
  • Monitor patients for the development of SPM
  • In clinical trials in patients with multiple myeloma receiving REVLIMID, an increase of hematologic solid tumor SPM, notably AML and MDS, have been observed
  • In patients receiving REVLIMID maintenance therapy following high-dose intravenous melphalan and auto-HSCT, hematologic SPM occurred in 7.5% of patients compared with 3.3% of patients receiving placebo
  • The incidence of hematologic plus solid tumor (excluding squamous cell carcinoma and basal cell carcinoma) SPM was 14.9% compared with 8.8% in patients receiving placebo with a median follow-up of 91.5 months
  • Non-melanoma skin cancer SPM, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving REVLIMID maintenance, compared to 2.6% in the placebo arm
  • In patients with ndMM treated with REVLIMID in combination with dexamethasone without melphalan, the frequency of AML and MDS cases was 0.4%
  • Patients who received REVLIMID-containing therapy until disease progression did not show a higher incidence of invasive SPM than patients treated in the fixed duration REVLIMID-containing arms

Maintenance Safety Profile Established in More Than 1000 Patients1

The adverse reactions listed from Maintenance Study 1 (US) included events reported post-transplant (completion of high-dose melphalan/auto-HSCT), and the maintenance treatment period. In Maintenance Study 2 (EU), the adverse reactions were from the maintenance treatment period only1,9

All Adverse Reactions in ≥5% of Patients and Corresponding Grade 3/4
Adverse Reactions ≥1% Reported in Study 1 and Study 21,9

Body System
Adverse Reaction
REVLIMID
(n=224)
n (%)
Placebo
(n=221)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropeniac%
177 (79.0) 94 (42.5)
Thrombocytopeniac%
162 (72.3) 101 (45.7)
Leukopeniac
51 (22.8) 25 (11.3)
Anemia
47 (21.0) 27 (12.2)
Lymphopenia
40 (17.9) 29 (13.1)
Pancytopeniacd%
1 (0.4) 0 (0.0)
Febrile neutropeniac
39 (17.4) 34 (15.4)
INFECTIONS AND INFESTATIONS#
Upper respiratory tract infectione
60 (26.8) 35 (15.8)
Neutropenic infection
40 (17.9) 19 (8.6)
Pneumonias*c%
31 (13.8) 15 (6.8)
Bronchitisc
10 (4.5) 9 (4.1)
Nasopharyngitise
5 (2.2) 2 (0.9)
Gastroenteritisc
0 (0.0) 0 (0.0)
Rhinitise
2 (0.9) 0 (0.0)
Sinusitise
8 (3.6) 3 (1.4)
Influenzac
8 (3.6) 5 (2.3)
Lung infectionc
21 (9.4) 2 (0.9)
Lower respiratory tract infectione
13 (5.8) 5 (2.3)
Infectionc
12 (5.4) 6 (2.7)
Urinary tract infectioncde
9 (4.0) 5 (2.3)
Lower respiratory tract infection bacteriald
6 (2.7) 1 (0.5)
Bacteremiad
5 (2.2) 0 (0.0)
Herpes zostercd
11 (4.9) 10 (4.5)
Sepsis*cd@
2 (0.9) 1 (0.5)
GASTROINTESTINAL DISORDERS
Diarrhea
122 (54.5) 83 (37.6)
Nauseae
33 (14.7) 22 (10.0)
Vomiting
17 (7.6) 12 (5.4)
Constipatione
12 (5.4) 8 (3.6)
Abdominal paine
8 (3.6) 7 (3.2)
Abdominal pain uppere
0 (0.0) 0 (0.0)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Asthenia
0 (0.0) 1 (0.5)
Fatigue
51 (22.8) 30 (13.6)
Pyrexiae
17 (7.6) 10 (4.5)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dry skine
9 (4.0) 4 (1.8)
Rash
71 (31.7) 48 (21.7)
Pruritus
9 (4.0) 4 (1.8)
NERVOUS SYSTEM DISORDERS
Paresthesiae
2 (0.9) 0 (0.0)
Peripheral neuropathy*e
34 (15.2) 30 (13.6)
Headached
11 (4.9) 8 (3.6)
INVESTIGATIONS
Alanine aminotransferase increased
16 (7.1) 3 (1.4)
Aspartate aminotransferase increasedd
13 (5.8) 5 (2.3)
METABOLISM AND NUTRITION DISORDERS
Hypokalemia
24 (10.7) 13 (5.9)
Dehydration
9 (4.0) 5 (2.3)
Hypophosphatemiad
16 (7.1) 15 (6.8)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Muscle spasmse
0 (0.0) 1 (0.5)
Myalgiae
7 (3.1) 8 (3.6)
Musculoskeletal paine
1 (0.4) 1 (0.5)
HEPATOBILIARY DISORDERS
Hyperbilirubinemiae
34 (15.2) 19 (8.6)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Coughe
23 (10.3) 12 (5.4)
Dyspneace
15 (6.7) 9 (4.1)
Rhinorrheae
0 (0.0) 3 (1.4)
Pulmonary embolismcde
0 (0.0) 0 (0.0)
VASCULAR DISORDERS
Deep vein thrombosis*cd%
8 (3.6) 2 (0.9)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED [INCL CYSTS AND POLYPS]
Myelodysplastic syndromecde
5 (2.2) 0 (0.0)
Body System
Adverse Reaction
REVLIMID
(n=224)
n (%)
Placebo
(n=221)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropeniac%
133 (59.4) 73 (33.0)
Thrombocytopeniac%
84 (37.5) 67 (30.3)
Leukopeniac
45 (20.1) 22 (10.0)
Anemia
23 (10.3) 18 (8.1)
Lymphopenia
37 (16.5) 26 (11.8)
Pancytopeniacd%
0 (0.0) 0 (0.0)
Febrile neutropeniac
39 (17.4) 34 (15.4)
INFECTIONS AND INFESTATIONS#
Upper respiratory tract infectione
7 (3.1) 9 (4.1)
Neutropenic infection
27 (12.1) 14 (6.3)
Pneumonias*c%
23 (10.3) 7 (3.2)
Bronchitisc
1 (0.4) 5 (2.3)
Nasopharyngitise
0 (0.0) 0 (0.0)
Gastroenteritisc
0 (0.0) 0 (0.0)
Rhinitise
0 (0.0) 0 (0.0)
Sinusitise
0 (0.0) 0 (0.0)
Influenzac
2 (0.9) 1 (0.5)
Lung infectionc
19 (8.5) 2 (0.9)
Lower respiratory tract infectione
6 (2.7) 4 (1.8)
Infectionc
9 (4.0) 5 (2.3)
Urinary tract infectioncde
4 (1.8) 4 (1.8)
Lower respiratory tract infection bacteriald
4 (1.8) 0 (0.0)
Bacteremiad
4 (1.8) 0 (0.0)
Herpes zostercd
3 (1.3) 2 (0.9)
Sepsis*cd@
0 (0.0) 0 (0.0)
GASTROINTESTINAL DISORDERS
Diarrhea
22 (9.8) 17 (7.7)
Nauseae
16 (7.1) 10 (4.5)
Vomiting
8 (3.6) 5 (2.3)
Constipatione
0 (0.0) 0 (0.0)
Abdominal paine
1 (0.4) 4 (1.8)
Abdominal pain uppere
0 (0.0) 0 (0.0)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Asthenia
0 (0.0) 0 (0.0)
Fatigue
21 (9.4) 9 (4.1)
Pyrexiae
2 (0.9) 2 (0.9)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dry skine
0 (0.0) 0 (0.0)
Rash
11 (4.9) 5 (2.3)
Pruritus
3 (1.3) 0 (0.0)
NERVOUS SYSTEM DISORDERS
Paresthesiae
0 (0.0) 0 (0.0)
Peripheral neuropathy*e
8 (3.6) 8 (3.6)
Headached
5 (2.2) 1 (0.5)
INVESTIGATIONS
Alanine aminotransferase increased
8 (3.6) 0 (0.0)
Aspartate aminotransferase increasedd
6 (2.7) 0 (0.0)
METABOLISM AND NUTRITION DISORDERS
Hypokalemia
16 (7.1) 12 (5.4)
Dehydration
7 (3.1) 3 (1.4)
Hypophosphatemiad
13 (5.8) 14 (6.3)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Muscle spasmse
0 (0.0) 0 (0.0)
Myalgiae
3 (1.3) 5 (2.3)
Musculoskeletal paine
0 (0.0) 0 (0.0)
HEPATOBILIARY DISORDERS
Hyperbilirubinemiae
4 (1.8) 2 (0.9)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Coughe
3 (1.3) 1 (0.5)
Dyspneace
8 (3.6) 4 (1.8)
Rhinorrheae
0 (0.0) 0 (0.0)
Pulmonary embolismcde
0 (0.0) 0 (0.0)
VASCULAR DISORDERS
Deep vein thrombosis*cd%
5 (2.2) 2 (0.9)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED [INCL CYSTS AND POLYPS]
Myelodysplastic syndromecde
2 (0.9) 0 (0.0)

All Adverse Reactions in ≥5% of Patients and Corresponding Grade 3/4
Adverse Reactions ≥1% Reported in Study 1 and Study 21,9

Body System
Adverse Reaction
REVLIMID
(n=293)
n (%)
Placebo
(n=280)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropeniac%
178 (60.8) 33 (11.8)
Thrombocytopeniac%
69 (23.5) 29 (10.4)
Leukopeniac
93 (31.7) 21 (7.5)
Anemia
26 (8.9) 15 (5.4)
Lymphopenia
13 (4.4) 3 (1.1)
Pancytopeniacd%
12 (4.1) 1 (0.4)
Febrile neutropeniac
7 (2.4) 1 (0.4)
INFECTIONS AND INFESTATIONS#
Upper respiratory tract infectione
32 (10.9) 18 (6.4)
Neutropenic infection
0 (0.0) 0 (0.0)
Pneumonias*c%
50 (17.1) 13 (4.6)
Bronchitisc
139 (47.4) 104 (37.1)
Nasopharyngitise
102 (34.8) 84 (30.0)
Gastroenteritisc
66 (22.5) 55 (19.6)
Rhinitise
44 (15.0) 19 (6.8)
Sinusitise
41 (14.0) 26 (9.3)
Influenzac
39 (13.3) 19 (6.8)
Lung infectionc
9 (3.1) 4 (1.4)
Lower respiratory tract infectione
4 (1.4) 4 (1.4)
Infectionc
17 (5.8) 5 (1.8)
Urinary tract infectioncde
22 (7.5) 17 (6.1)
Lower respiratory tract infection bacteriald
0 (0.0) 0 (0.0)
Bacteremiad
0 (0.0) 0 (0.0)
Herpes zostercd
29 (9.9) 25 (8.9)
Sepsis*cd@
6 (2.0) 1 (0.4)
GASTROINTESTINAL DISORDERS
Diarrhea
114 (38.9) 34 (12.1)
Nauseae
31 (10.6) 28 (10.0)
Vomiting
16 (5.5) 15 (5.4)
Constipatione
37 (12.6) 25 (8.9)
Abdominal paine
31 (10.6) 15 (5.4)
Abdominal pain uppere
20 (6.8) 12 (4.3)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Asthenia
87 (29.7) 53 (18.9)
Fatigue
31 (10.6) 15 (5.4)
Pyrexiae
60 (20.5) 26 (9.3)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dry skine
31 (10.6) 21 (7.5)
Rash
22 (7.5) 17 (6.1)
Pruritus
21 (7.2) 25 (8.9)
NERVOUS SYSTEM DISORDERS
Paresthesiae
39 (13.3) 30 (10.7)
Peripheral neuropathy*e
29 (9.9) 15 (5.4)
Headached
25 (8.5) 21 (7.5)
INVESTIGATIONS
Alanine aminotransferase increased
5 (1.7) 5 (1.8)
Aspartate aminotransferase increasedd
2 (0.7) 5 (1.8)
METABOLISM AND NUTRITION DISORDERS
Hypokalemia
12 (4.1) 1 (0.4)
Dehydration
0 (0.0) 0 (0.0)
Hypophosphatemiad
0 (0.0) 1 (0.4)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Muscle spasmse
98 (33.4) 43 (15.4)
Myalgiae
19 (6.5) 12 (4.3)
Musculoskeletal paine
19 (6.5) 11 (3.9)
HEPATOBILIARY DISORDERS
Hyperbilirubinemiae
4 (1.4) 1 (0.4)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Coughe
80 (27.3) 56 (20.0)
Dyspneace
17 (5.8) 9 (3.2)
Rhinorrheae
15 (5.1) 6 (2.1)
Pulmonary embolismcde
3 (1.0) 0 (0.0)
VASCULAR DISORDERS
Deep vein thrombosis*cd%
7 (2.4) 1 (0.4)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED [INCL CYSTS AND POLYPS]
Myelodysplastic syndromecde
3 (1.0) 0 (0.0)
Body System
Adverse Reaction
REVLIMID
(n=293)
n (%)
Placebo
(n=280)
n (%)
BLOOD AND LYMPHATIC SYSTEM DISORDERS
Neutropeniac%
158 (53.9) 21 (7.5)
Thrombocytopeniac%
38 (13.0) 8 (2.9)
Leukopeniac
71 (24.2) 5 (1.8)
Anemia
11 (3.8) 3 (1.1)
Lymphopenia
11 (3.8) 2 (0.7)
Pancytopeniacd%
7 (2.4) 1 (0.4)
Febrile neutropeniac
5 (1.7) 1 (0.4)
INFECTIONS AND INFESTATIONS#
Upper respiratory tract infectione
1 (0.3) 0 (0.0)
Neutropenic infection
0 (0.0) 0 (0.0)
Pneumonias*c%
27 (9.2) 5 (1.8)
Bronchitisc
4 (1.4) 1 (0.4)
Nasopharyngitise
1 (0.3) 0 (0.0)
Gastroenteritisc
6 (2.0) 0 (0.0)
Rhinitise
0 (0.0) 0 (0.0)
Sinusitise
0 (0.0) 1 (0.4)
Influenzac
3 (1.0) 0 (0.0)
Lung infectionc
1 (0.3) 0 (0.0)
Lower respiratory tract infectione
0 (0.0) 2 (0.7)
Infectionc
0 (0.0) 0 (0.0)
Urinary tract infectioncde
1 (0.3) 0 (0.0)
Lower respiratory tract infection bacteriald
0 (0.0) 0 (0.0)
Bacteremiad
0 (0.0) 0 (0.0)
Herpes zostercd
6 (2.0) 2 (0.7)
Sepsis*cd@
4 (1.4) 1 (0.4)
GASTROINTESTINAL DISORDERS
Diarrhea
7 (2.4) 0 (0.0)
Nauseae
0 (0.0) 0 (0.0)
Vomiting
1 (0.3) 0 (0.0)
Constipatione
2 (0.7) 0 (0.0)
Abdominal paine
1 (0.3) 1 (0.4)
Abdominal pain uppere
1 (0.3) 0 (0.0)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Asthenia
10 (3.4) 2 (0.7)
Fatigue
3 (1.0) 0 (0.0)
Pyrexiae
1 (0.3) 0 (0.0)
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Dry skine
0 (0.0) 0 (0.0)
Rash
3 (1.0) 0 (0.0)
Pruritus
2 (0.7) 0 (0.0)
NERVOUS SYSTEM DISORDERS
Paresthesiae
1 (0.3) 0 (0.0)
Peripheral neuropathy*e
4 (1.4) 2 (0.7)
Headached
0 (0.0) 0 (0.0)
INVESTIGATIONS
Alanine aminotransferase increased
0 (0.0) 1 (0.4)
Aspartate aminotransferase increasedd
0 (0.0) 0 (0.0)
METABOLISM AND NUTRITION DISORDERS
Hypokalemia
2 (0.7) 0 (0.0)
Dehydration
0 (0.0) 0 (0.0)
Hypophosphatemiad
0 (0.0) 0 (0.0)
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Muscle spasmse
1 (0.3) 0 (0.0)
Myalgiae
2 (0.7) 1 (0.4)
Musculoskeletal paine
0 (0.0) 0 (0.0)
HEPATOBILIARY DISORDERS
Hyperbilirubinemiae
2 (0.7) 0 (0.0)
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS
Coughe
0 (0.0) 0 (0.0)
Dyspneace
2 (0.7) 0 (0.0)
Rhinorrheae
0 (0.0) 0 (0.0)
Pulmonary embolismcde
2 (0.7) 0 (0.0)
VASCULAR DISORDERS
Deep vein thrombosis*cd%
4 (1.4) 1 (0.4)
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED [INCL CYSTS AND POLYPS]
Myelodysplastic syndromecde
1 (0.3) 0 (0.0)

Note: AEs are coded to body system/adverse reaction using MedDRA v15.1. A subject with multiple occurrences of an AE is counted only once in each AE category.

a All treatment-emergent AEs in at least 5% of patients in the Lenalidomide Maintenance group and at least 2% higher frequency (%) than the Placebo Maintenance group.
b All grade 3 or 4 treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the Placebo Maintenance group.
c All serious treatment-emergent AEs in at least 1% of patients in the Lenalidomide Maintenance group and at least 1% higher frequency (%) than the Placebo Maintenance group.
d Footnote “a” not applicable for either study.
e Footnote “b” not applicable for either study.
@ ADRs where at least one resulted in a fatal outcome.
% ADRs where at least one was considered to be Life Threatening (if the outcome of the event was death, it is included with death cases).
# All adverse reactions under Body System of Infections and Infestation except for rare infections of Public Health interest will be considered listed.
* Adverse Reactions for combined ADR terms (based on relevant TEAE PTs included in Maintenance Studies 1 and 2
[per MedDRA v15.1]):
Pneumonias: Bronchopneumonia, Lobar pneumonia, Pneumocystis jiroveci pneumonia, Pneumonia, Pneumonia klebsiella, Pneumonia legionella, Pneumonia mycoplasmal, Pneumonia pneumococcal, Pneumonia streptococcal, Pneumonia viral, Lung disorder, Pneumonitis
Sepsis: Bacterial sepsis, Pneumococcal sepsis, Sepsis, Septic shock, Staphylococcal sepsis
Peripheral neuropathy: Neuropathy peripheral, Peripheral motor neuropathy, Peripheral sensory neuropathy, Polyneuropathy
Deep vein thrombosis: Deep vein thrombosis, Thrombosis, Venous thrombosis

NEXT: Using REVLIMID in patients who received ≥1 prior therapy

INDICATIONS

REVLIMID® (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of patients with multiple myeloma (MM)

REVLIMID is indicated as maintenance therapy in patients with MM following autologous hematopoietic stem cell transplantation (auto-HSCT)

REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials

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IMPORTANT SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity
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 embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting REVLIMID treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after REVLIMID treatment. To avoid embryo-fetal exposure to lenalidomide, REVLIMID is only available through a restricted distribution program, the REVLIMID REMS® program.

Information about the REVLIMID REMS® program is available at www.celgeneriskmanagement.com or by calling the manufacturer’s toll-free number 1-888-423-5436.

Hematologic Toxicity (Neutropenia and Thrombocytopenia)
REVLIMID can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with del 5q MDS 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 MDS 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.

Venous and Arterial Thromboembolism
REVLIMID has demonstrated a significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with MM who were treated with REVLIMID and dexamethasone therapy. Monitor for and advise patients about signs and symptoms of thromboembolism. Advise patients to seek immediate medical care if they develop symptoms such as shortness of breath, chest pain, or arm or leg swelling. Thromboprophylaxis is recommended and the choice of regimen should be based on an assessment of the patient's underlying risks.

CONTRAINDICATIONS

Pregnancy: REVLIMID can cause fetal harm when administered to a pregnant female and is contraindicated in females who are pregnant. 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 risk to the fetus

Allergic Reactions: REVLIMID is contraindicated in patients who have demonstrated hypersensitivity (e.g., angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis) to lenalidomide

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity: See Boxed WARNINGS 

  • Females of Reproductive Potential: See Boxed WARNINGS
  • Males: Lenalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking REVLIMID and for up to 4 weeks after discontinuing REVLIMID, even if they have undergone a successful vasectomy. Male patients taking REVLIMID must not donate sperm
  • Blood Donation: Patients must not donate blood during treatment with REVLIMID and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to REVLIMID

REVLIMID REMS® Program: See Boxed WARNINGS: Prescribers and pharmacies must be certified with the REVLIMID REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive REVLIMID. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements

Hematologic Toxicity: REVLIMID can cause significant neutropenia and thrombocytopenia. Monitor patients with neutropenia for signs of infection. Advise patients to observe for bleeding or bruising, especially with use of concomitant medications that may increase risk of bleeding. MM: Patients taking REVLIMID/dex or REVLIMID as maintenance therapy should have their complete blood counts (CBC) assessed every 7 days for the first 2 cycles, on days 1 and 15 of cycle 3, and every 28 days thereafter

Venous and Arterial Thromboembolism: See Boxed WARNINGS: Venous thromboembolic events (DVT and PE) and arterial thromboses (MI and CVA) are increased in patients treated with REVLIMID. Patients with known risk factors, including prior thrombosis, may be at greater risk and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended and the regimen should be based on patient's underlying risks. ESAs and estrogens may further increase the risk of thrombosis and their use should be based on a benefit-risk decision

Increased Mortality in Patients with CLL: In a clinical trial in the first-line treatment of patients with CLL, single agent REVLIMID therapy increased the risk of death as compared to single agent chlorambucil. Serious adverse cardiovascular reactions, including atrial fibrillation, myocardial infarction, and cardiac failure, occurred more frequently in the REVLIMID arm. REVLIMID is not indicated and not recommended for use in CLL outside of controlled clinical trials

Second Primary Malignancies (SPM): In clinical trials in patients with MM receiving REVLIMID, an increase of hematologic plus solid tumor SPM, notably AML and MDS, have been observed. Monitor patients for the development of SPM. Take into account both the potential benefit of REVLIMID and risk of SPM when considering treatment

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with REVLIMID/dex. Pre-existing viral liver disease, elevated baseline liver enzymes, and concomitant medications may be risk factors. Monitor liver enzymes periodically. Stop REVLIMID upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered

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 treatment should be evaluated in patients with lactose intolerance

Tumor Lysis Syndrome (TLS): Fatal instances of TLS have been reported during treatment with lenalidomide. The patients at risk of TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken

Tumor Flare Reaction (TFR): TFR has occurred during investigational use of lenalidomide for CLL and lymphoma. Monitoring and evaluation for TFR is recommended in patients with MCL. Tumor flare may mimic the progression of disease (PD). In patients with Grade 3 or 4 TFR, it is recommended to withhold treatment with REVLIMID until TFR resolves to ≤Grade 1. REVLIMID may be continued in patients with Grade 1 and 2 TFR without interruption or modification, at the physician's discretion

Impaired Stem Cell Mobilization: A decrease in the number of CD34+ cells collected after treatment (>4 cycles) with REVLIMID has been reported. Consider early referral to transplant center to optimize timing of the stem cell collection

Thyroid Disorders: Both hypothyroidism and hyperthyroidism have been reported. Measure thyroid function before start of REVLIMID treatment and during therapy

ADVERSE REACTIONS

Multiple Myeloma

  • In newly diagnosed: The most frequently reported Grade 3 or 4 reactions included neutropenia, anemia, thrombocytopenia, pneumonia, asthenia, fatigue, back pain, hypokalemia, rash, cataract, lymphopenia, dyspnea, DVT, hyperglycemia, and leukopenia. The highest frequency of infections occurred in Arm Rd Continuous (75%)  compared to Arm MPT (56%). There were more Grade 3 and 4 and serious adverse reactions of infection in Arm Rd Continuous than either Arm MPT or Rd18
  • The most common adverse reactions reported in ≥20% (Arm Rd Continuous): diarrhea (46%), anemia (44%), neutropenia (35%), fatigue (33%), back pain (32%), asthenia (28%), insomnia (28%), rash (26%), decreased appetite (23%), cough (23%), dyspnea (22%), pyrexia (21%), abdominal pain (21%), muscle spasms (20%), and thrombocytopenia (20%)
  • Maintenance Therapy Post-Auto HSCT: The most frequently reported Grade 3 or 4 reactions in ≥20% (REVLIMID arm) included neutropenia, thrombocytopenia, and leukopenia. The serious adverse reactions of lung infection and neutropenia (more than 4.5%) occurred in the REVLIMID arm
  • The most frequently reported adverse reactions in ≥20% (REVLIMID arm) across both maintenance studies (Study 1, Study 2) were neutropenia (79%, 61%), thrombocytopenia (72%, 24%), leukopenia (23%, 32%), anemia (21%, 9%), upper respiratory tract infection (27%, 11%), bronchitis (5%, 47%), nasopharyngitis (2%, 35%), cough (10%, 27%), gastroenteritis (0%, 23%), diarrhea (55%, 39%), rash (32%, 8%), fatigue (23%, 11%), asthenia (0%, 30%), muscle spasm (0%, 33%), and pyrexia (8%, 21%)
  • After at least one prior therapy: The most common adverse reactions reported in ≥20% (REVLIMID/dex vs dex/placebo): fatigue (44% vs 42%), neutropenia (42% vs 6%), constipation (41% vs 21%), diarrhea (39% vs 27%), muscle cramp (33% vs 21%), anemia (31% vs 24%), pyrexia (28% vs 23%), peripheral edema (26% vs 21%), nausea (26% vs 21%), back pain (26% vs 19%), upper respiratory tract infection (25% vs 16%), dyspnea (24% vs 17%), dizziness (23% vs 17%), thrombocytopenia (22% vs 11%), rash (21% vs 9%), tremor (21% vs 7%), and weight decreased (20% vs 15%)

DRUG INTERACTIONS

Periodic monitoring of digoxin plasma levels is recommended due to increased Cmax and AUC with concomitant REVLIMID therapy. Patients taking concomitant therapies such as erythropoietin stimulating agents or estrogen containing therapies may have an increased risk of thrombosis. It is not known whether there is an interaction between dex and warfarin. Close monitoring of PT and INR is recommended in patients with MM taking concomitant warfarin

USE IN SPECIFIC POPULATIONS

  • PREGNANCY: See Boxed WARNINGS: If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a REVLIMID pregnancy exposure registry that monitors pregnancy outcomes in females exposed to REVLIMID during pregnancy as well as female partners of male patients who are exposed to REVLIMID. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to REVLIMID to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436
  • LACTATION: There is no information regarding the presence of lenalidomide in human milk, the effects of REVLIMID on the breastfed infant, or the effects of REVLIMID on milk production. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from REVLIMID, advise female patients not to breastfeed during treatment with REVLIMID
  • PEDIATRIC USE: Safety and effectiveness have not been established in pediatric patients
  • RENAL IMPAIRMENT: Adjust the starting dose of REVLIMID based on creatinine clearance value and in patients on dialysis

Please see full Prescribing Information, including Boxed WARNINGS.

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INDICATIONS

REVLIMID® (lenalidomide) in combination with dexamethasone (dex) is indicated for the treatment of

IMPORTANT SAFETY INFORMATION

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity
Do not use REVLIMID during pregnancy.