Revlimid

Revlimid

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 2, 3, and 4 summarize the adverse reactions reported for REVLIMID/dexamethasone and placebo/dexamethasone groups.

Table 2: 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)

Table 3: 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)

Table 4: 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)
aAll 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 ≥ 1% 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 5 summarizes the adverse events that were reported in ≥ 5% of the REVLIMID treated patients in the del 5q MDS clinical study. Table 6 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 5: Summary of Adverse Events Reported in ≥ 5% of the REVLIMID Treated Patients in del 5q MDS Clinical Study

System organ class/Preferred term a 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)
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 6: 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 (M)
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)
1 Adverse 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 5 or 6 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, pancreatitis due 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 infestations infection 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, Pseudomonas infection, 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, dyspnea exacerbated, 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

Clinical Trials Experience in Mantle Cell Lymphoma

In the MCL trial, a total of 134 patients received at least 1 dose of REVLIMID. Their median age was 67 (range 43-83) years, 128/134 (96%) were Caucasian, 108/134 (81%) were males and 82/134 (61%) had duration of MCL for at least 3 years.

Table 7 summarizes the most frequently observed adverse reactions regardless of relationship to treatment with REVLIMID. Across the 134 patients treated in this study, median duration of treatment was 95 days (1-1002 days). Seventy-eight patients (58%) received 3 or more cycles of therapy, 53 patients (40%) received 6 or more cycles, and 26 patients (19%) received 12 or more cycles. Seventy-six patients (57%) underwent at least one dose interruption due to adverse events, and 51 patients (38%) underwent at least one dose reduction due to adverse events. Twenty-six patients (19%) discontinued treatment due to adverse events.

Table 7: Incidence of Adverse Reactions ( ≥ 10%) or Grade 3 / 4 AE (in at least 2 patients) in Mantle Cell Lymphoma

System Organ Class/Preferred Term All AEs1
(N=134)
n (%)
Grade 3/4 AEs2
(N=134)
n (%)
General disorders and administration site conditions
Fatigue 45 (34) 9 (7)
Pyrexia$ 31(23) 3 (2)
Edema peripheral 21 (16) 0
Asthenia$ 19 (14) 4 (3)
General physical health deterioration 3 (2) 2 (1)
Gastrointestinal disorders
Diarrhea$ 42 (31) 8 (6)
Nausea$ 40 (30) 1 ( < 1)
Constipation 21(16) 1 ( < 1)
Vomiting$ 16 (12) 1 ( < 1)
Abdominal pain$ 13 (10) 5 (4)
Musculoskeletal and connective tissue disorders
Back pain 18 (13) 2 (1)
Muscle spasms 17 (13) 1 ( < 1)
Arthralgia 11 (8) 2 (1)
Muscular weakness$ 8 (6) 2 (1)
Respiratory, thoracic and mediastinal disorders
Cough 38 (28) 1 ( < 1)
Dyspnea$ 24 (18) 8 (6)
Pleural Effusion 10 (7) 2 (1)
Hypoxia 3 (2) 2 (1)
Pulmonary embolism 3 (2) 2 (1)
Respiratory distress$ 2 (1) 2 (1)
Oropharyngeal pain 13 (10) 0
Infections and infestations
Pneumonia@ $ 19 (14) 12 (9)
Upper respiratory tract infection 17 (13) 0
Cellulitis$ 3 (2) 2 (1)
Bacteremia$ 2 (1) 2 (1)
Staphylococcal sepsis$ 2 (1) 2 (1)
Urinary tract infection$ 5 (4) 2 (1)
Skin and subcutaneous tissue disorders
Rash + 30 (22) 2 (1)
Pruritus 23 (17) 1 ( < 1)
Blood and lymphatic system disorders
Neutropenia 65 (49) 58(43)
Thrombocytopenia%$ 48 (36) 37 (28)
Anemia$ 41 (31) 15(11)
Leukopenia$ 20 (15) 9 (7)
Lymphopenia 10 (7) 5 (4)
Febrile neutropenia$ 8 (6) 8 (6)
Metabolism and nutrition disorders
Decreased appetite 19 (14) 1 ( < 1)
Hypokalemia 17 (13) 3 (2)
Dehydration$ 10 (7) 4 (3)
Hypocalcemia 4 (3) 2 (1)
Hyponatremia 3 (2) 3 (2)
Renal and urinary disorders
Renal failure$ 5 (4) 2 (1)
Vascular disorders
Hypotension@ $ 9 (7) 4 (3)
Deep vein thrombosis$ 5 (4) 5 (4)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor flare 13 (10) 0
Squamous cell carcinoma of skin$ 4 (3) 4 (3)
Investigations
Weight decreased 17 (13) 0
1MCL trial AEs – All treatment emergent AEs with > 10% of subjects
2MCL trial Grade 3/4 AEs – All treatment-emergent Grade 3/4 AEs in 2 or more subjects
$MCL trial Serious AEs – All treatment-emergent SAEs in 2 or more subjects
@-AEs where at least one resulted in a fatal outcome
%-AEs 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 PTs under SOC of Infections except for rare infections of Public Health interest will be considered listed
+-All PTs under HLT of Rash will be considered listed

The following adverse events which have occurred in other indications and not described above have been reported (5-10%) in patients treated with REVLIMID monotherapy for mantle cell lymphoma.

General disorders and administration site conditions: Chills

Musculoskeletal and connective tissue disorders: Pain in extremity

Nervous system disorders: Dysguesia, headache, neuropathy peripheral

Infections and infestations: Respiratory tract infection, sinusitis, nasopharyngitis

Skin and subcutaneous tissue disorders: Dry skin, night sweats

The following serious adverse events not described above and reported in 2 or more patients treated with REVLIMID monotherapy for mantle cell lymphoma.

Respiratory, Thoracic and Mediastinal Disorders: Chronic obstructive pulmonary disease

Infections and Infestations: Clostridium difficile colitis, sepsis

Neoplasms benign, malignant and unspecified (incl cysts and polyps): Basal cell carcinoma

Cardiac Disorder: Supraventricular tachycardia

Postmarketing Experience

The following adverse drug reactions have been identified from the worldwide post-marketing experience with REVLIMID: Allergic conditions (angioedema, SJS, TEN), tumor lysis syndrome (TLS) and tumor flare reaction (TFR), pneumonitis, hepatic failure, including fatality, toxic hepatitis, cytolytic hepatitis, cholestatic hepatitis, and mixed cytolytic/cholestatic hepatitis and transient abnormal liver laboratory tests. 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 [see WARNINGS AND PRECAUTIONS].

Cases of hypothyroidism and hyperthyroidism have also been reported. Optimal control of thyroid function is recommended before start of treatment. Baseline and ongoing monitoring of thyroid function is recommended.

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

DRUG INTERACTIONS

Results from human in vitro 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 vitro studies demonstrated that REVLIMID is not a substrate of human breast cancer resistance protein (BCRP), multidrug resistance protein (MRP) transporters MRP1, MRP2, or MRP3, organic anion transporters (OAT) OAT1 and OAT3, organic anion transporting polypeptide 1B1 (OATP1B1 or OATP2), organic cation transporters (OCT) OCT1 and OCT2, multidrug and toxin extrusion protein (MATE) MATE1, and organic cation transporters novel (OCTN) OCTN1 and OCTN2.

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].

Read the Revlimid Drug Interactions Center for a complete guide to possible interactions

Last reviewed on RxList: 11/14/2013
This monograph has been modified to include the generic and brand name in many instances.

A A A

Revlimid - User Reviews

Revlimid User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Revlimid sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.

advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations