POMALYST SIDE EFFECTS
- Generic Name: pomalidomide capsules
- Brand Name: Pomalyst
- Drug Class: Antineoplastics, Angiogenesis Inhibitor
SIDE EFFECTS
The following clinically significant adverse reactions are described in detail in other labeling sections:
- Embryo-Fetal Toxicity
- Venous and Arterial Thromboembolism
- Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone
- Hematologic Toxicity
- Hepatotoxicity
- Severe Cutaneous Reactions
- Dizziness and Confusional State
- Neuropathy
- Risk of Second Primary Malignancies
- Tumor Lysis Syndrome
- Hypersensitivity
Clinical Trials Experience
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.
Multiple Myeloma (MM)
In Trial 1, data were evaluated from 219 patients (safety population) who received treatment with POMALYST + Low-dose Dex (112 patients) or POMALYST alone (107 patients). Median number of treatment cycles was 5. Sixty-seven percent of patients in the study had a dose interruption of either drug due to adverse reactions. Forty-two percent of patients in the study had a dose reduction of either drug due to adverse reactions. The discontinuation rate due to adverse reactions was 11%.
In Trial 2, data were evaluated from 450 patients (safety population) who received treatment with POMALYST + Low-dose Dex (300 patients) or High-dose Dexamethasone (High-dose Dex) (150 patients). The median number of treatment cycles for the POMALYST + Low-dose Dex arm was 5. In the POMALYST + Low-dose Dex arm, 67% of patients had a dose interruption of POMALYST, the median time to the first dose interruption of POMALYST was 4.1 weeks. Twenty-seven percent of patients had a dose reduction of POMALYST, the median time to the first dose reduction of POMALYST was 4.5 weeks. Eight percent of patients discontinued POMALYST due to adverse reactions.
Tables 1 and 2 summarize the adverse reactions reported in Trials 1 and 2, respectively.
Table 1: Adverse Reactions in Any POMALYST Treatment Arm in Trial 1*
| Body System Adverse Reaction |
All Adverse Reactions ≥10% in Either Arm | Grade 3 or 4 ≥5% in Either Arm | ||
| POMALYSTa (N=107) |
POMALYST + Low-dose Dex (N=112) |
POMALYST (N=107) |
POMALYST + Low-dose Dex (N=112) |
|
| Number (%) of patients with at least one adverse reaction | 107 (100) | 112 (100) | 98 (92) | 102 (91) |
| Blood and lymphatic system disorders | ||||
| Neutropenia b | 57 (53) | 55 (49) | 51 (48) | 46 (41) |
| Anemia b | 41 (38) | 47 (42) | 25 (23) | 24 (21) |
| Thrombocytopenia b | 28 (26) | 26 (23) | 24 (22) | 21 (19) |
| Leukopenia | 14 (13) | 22 (20) | 7 (7) | 11 (10) |
| Febrile neutropenia b | <10% | <10% | 6 (6) | 3 (3) |
| Lymphopenia | 4 (4) | 17 (15) | 2 (2) | 8 (7) |
| General disorders and administration site conditions | ||||
| Fatigue and asthenia b | 62 (58) | 70 (63) | 13 (12) | 19 (17) |
| Edema peripheral | 27 (25) | 19 (17) | 0 (0.0) | 0 (0.0) |
| Pyrexia b | 25 (23) | 36 (32) | <5% | <5% |
| Chills | 11 (10) | 14 (13) | 0 (0.0) | 0 (0.0) |
| Gastrointestinal disorders | ||||
| Nausea b | 39 (36) | 27 (24) | <5% | <5% |
| Constipation b | 38 (36) | 41 (37) | <5% | <5% |
| Diarrhea | 37 (35) | 40 (36) | <5% | <5% |
| Vomiting b | 15 (14) | 16(14) | <5% | 0 (0.0) |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain b | 37 (35) | 36 (32) | 15 (14) | 11(10) |
| Musculoskeletal chest pain | 25 (23) | 22 (20) | <5% | 0 (0.0) |
| Muscle spasms | 23 (21) | 22 (20) | <5% | <5% |
| Arthralgia | 18 (17) | 17 (15) | <5% | <5% |
| Muscular weakness | 15 (14) | 15 (13) | 6 (6) | 4 (4) |
| Bone pain | 13 (12) | 8 (7) | <5% | <5% |
| Musculoskeletal pain | 13 (12) | 19 (17) | <5% | <5% |
| Pain in extremity | 8 (7) | 16 (14) | 0 (0.0) | <5% |
| Infections and infestations | ||||
| Upper respiratory tract infection | 40 (37) | 32 (29) | <5% | <5% |
| Pneumonia b | 30 (28) | 38 (34) | 21 (20) | 32 (29) |
| Urinary tract infection b | 11 (10) | 19 (17) | 2 (2) | 10 (9) |
| Sepsis b | <10% | <10% | 6 (6) | 5(4) |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 25 (23) | 21 (19) | <5% | 0 (0.0) |
| Hypercalcemia b | 23 (21) | 13 (12) | 11(10) | 1 (<1) |
| Hypokalemia | 13 (12) | 13 (12) | <5% | <5% |
| Hyperglycemia | 12 (11) | 17 (15) | <5% | <5% |
| Hyponatremia | 12 (11) | 14 (13) | <5% | <5% |
| Dehydration b | <10% | <10% | 5 (4.7) | 6 (5.4) |
| Hypocalcemia | 6 (6) | 13 (12) | 0 (0.0) | <5% |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea b | 38 (36) | 50 (45) | 8(7) | 14(13) |
| Cough | 18 (17) | 25 (22) | 0 (0.0) | 0 (0.0) |
| Epistaxis | 18 (17) | 12 (11) | <5% | 0 (0.0) |
| Productive cough | 10 (9) | 14 (13) | 0 (0.0) | 0 (0.0) |
| Oropharyngeal pain | 6 (6) | 12 (11) | 0 (0.0) | 0 (0.0) |
| Nervous system disorders | ||||
| Dizziness | 24 (22) | 20 (18) | <5% | <5% |
| Peripheral neuropathy | 23 (21) | 20 (18) | 0 (0.0) | 0 (0.0) |
| Headache | 16 (15) | 15 (13) | 0 (0.0) | <5% |
| Tremor | 11 (10) | 15 (13) | 0 (0.0) | 0 (0.0) |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 22 (21) | 18(16) | 0 (0.0) | <5% |
| Pruritus | 16 (15) | 10 (9) | 0 (0.0) | 0 (0.0) |
| Dry skin | 10 (9) | 12 (11) | 0 (0.0) | 0 (0.0) |
| Hyperhidrosis | 8 (7) | 18 (16) | 0 (0.0) | 0 (0.0) |
| Night sweats | 5 (5) | 14 (13) | 0 (0.0) | 0 (0.0) |
| Investigations | ||||
| Blood creatinine increased b | 20 (19) | 11(10) | 6(6) | 3(3) |
| Weight decreased | 16 (15) | 10 (9) | 0 (0.0) | 0 (0.0) |
| Weight increased | 1 (<1) | 12 (11) | 0 (0.0) | 0 (0.0) |
| Psychiatric disorders | ||||
| Anxiety | 14 (13) | 8 (7) | 0 (0.0) | 0 (0.0) |
| Confusional state b | 13 (12) | 15 (13) | 6 (6) | 3 (3) |
| Insomnia | 7 (7) | 18 (16) | 0 (0.0) | 0 (0.0) |
| Renal and urinary disorders | ||||
| Renal failure b | 16 (15) | 11 (10) | 9 (8) | 8 (7) |
| * Regardless of attribution of relatedness to POMALYST. a POMALYST alone arm includes all patients randomized to the POMALYST alone arm who took study drug; 61 of the 107 patients had dexamethasone added during the treatment period. b Serious adverse reactions were reported in at least 2 patients in any POMALYST treatment arm. Data cutoff: 01 March 2013 |
||||
Table 2: Adverse Reactions in Trial 2
| Body System Adverse Reaction |
All Adverse Reactions (≥5% in POMALYST + Low-dose Dex arm, and at least 2% higher than the High-dose-Dex arm) | Grade 3 or 4 (≥1% in POMALYST + Low-dose Dex arm, and at least 1% higher than the High-dose-Dex arm) | ||
| POMALYST + Low-dose Dex (N=300) |
High-dose Dex (N=150) |
POMALYST + Low-dose Dex (N=300) |
High-dose Dex (N=150) |
|
| Number (%) of patients with at least one adverse reaction | 297 (99) | 149 (99) | 259 (86) | 127 (85) |
| Blood and lymphatic system disorders | ||||
| Neutropenia b | 154 (51) | 31 (21) | 145 (48) | 24 (16) |
| Thrombocytopenia | 89 (30)a | 44 (29)a | 66 (22)a | 39 (26)a |
| Leukopenia | 38 (13) | 8 (5) | 27 (9) | 5 (3) |
| Febrile neutropenia b | 28 (9) | 0 (0.0) | 28 (9) | 0 (0.0) |
| General disorders and administration site conditions | ||||
| Fatigue and asthenia | 140 (47) | 64 (43) | 26 (9) a | 18(12) a |
| Pyrexia b | 80 (27) | 35 (23) | 9(3) a | 7(5) a |
| Edema peripheral | 52 (17) | 17(11) | 4(1) a | 3 (2) a |
| Pain | 11 (4) a | 3 (2) a | 5(2) | 1(<1) |
| Infections and infestations | ||||
| Upper respiratory tract infection b | 93 (31) | 19 (13) | 9 (3) | 1 (<1) |
| Pneumonia b | 58 (19) | 20(13) | 47 (16) | 15 (10) |
| Neutropenic sepsis b | 3(1) a | 0 (0.0)a | 3(1) | 0 (0.0) |
| Gastrointestinal disorders | ||||
| Diarrhea | 66 (22) | 28 (19) | 3 (1) a | 2 (1) a |
| Constipation | 65 (22) | 22 (15) | 7 (2) | 0 (0.0) |
| Nausea | 45 (15) | 17 (11) | 3 (1) a | 2 (1) a |
| Vomiting | 23 (8) | 6 (4) | 3 (1) | 0 (0.0) |
| Musculoskeletal and connective tissue disorders | ||||
| Back pain b | 59 (20) | 24 (16) | 15 (5) | 6 (4) |
| Bone pain b | 54 (18) | 21 (14) | 22 (7) | 7 (5) |
| Muscle spasms | 46 (15) | 11(7) | 1(<1) a | 1(<1) a |
| Arthralgia | 26 (9) | 7 (5) | 2 (<1) a | 1(<1) a |
| Pain in extremity | 20 (7) a | 9 (6) a | 6(2) | 0 (0.0) |
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnea b | 76 (25) | 25 (17) | 17(6) | 7(5) |
| Cough | 60 (20) | 15 (10) | 2 (<1) a | 1(<1) a |
| Chronic obstructive pulmonary disease b | 5 (2) a | 0 (0.0)a | 4 (1) | 0 (0.0) |
| Nervous system disorders | ||||
| Peripheral neuropathy | 52 (17) | 18 (12) | 5 (2) a | 2 (1) a |
| Dizziness | 37 (12) | 14 (9) | 4 (1) a | 2 (1) a |
| Headache | 23 (8) | 8 (5) | 1 (<1) a | 0 (0.0)a |
| Tremor | 17 (6) | 2 (1) | 2 (<1) a | 0 (0.0)a |
| Depressed level of consciousness | 5 (2) a | 0 (0.0)a | 3 (1) | 0 (0.0) |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 38 (13) | 12 (8) | 3 (1) a | 2 (1) a |
| Hypokalemia | 28 (9) a | 12 (8) a | 12 (4) | 4 (3) |
| Hypocalcemia | 12 (4) a | 9 (6) a | 5 (2) | 1 (<1) |
| Skin and subcutaneous tissue disorders | ||||
| Rash | 23 (8) | 2(1) | 3(1) | 0 (0.0) |
| Pruritus | 22 (7) | 5(3) | 0 (0.0)a | 0 (0.0) a |
| Hyperhidrosis | 15(5) | 1(<1) | 0 (0.0)a | 0 (0.0) a |
| Investigations | ||||
| Neutrophil count decreased | 15 (5) | 1(<1) | 14 (5) | 1(<1) |
| Platelet count decreased | 10 (3) a | 3 (2) a | 8(3) | 2 (1) |
| White blood cell count decreased | 8 (3) a | 1 (<1) a | 8(3) | 0 (0.0) |
| Alanine aminotransferase increased | 7 (2) a | 2 (1) a | 5(2) | 0 (0.0) |
| Aspartate aminotransferase increased | 4 (1) a | 2 (1) a | 3(1) | 0 (0.0) |
| Lymphocyte count decreased | 3 (1) a | 1 (<1) a | 3(1) | 0 (0.0) |
| Renal and urinary disorders | ||||
| Renal failure | 31 (10) a | 18 (12) a | 19 (6) | 8 (5) |
| Injury, poisoning and procedural complications | ||||
| Femur fracture b | 5 (2) a | 1 (<1) a | 5 (2) | 1 (<1) |
| Reproductive system and breast disorders | ||||
| Pelvic pain | 6 (2) a | 3 (2) a | 4(1) | 0 (0.0) |
| a Percentage did not meet the criteria to be considered as an adverse reaction for POMALYST for that category of event (i.e., all adverse events or Grade 3 or 4 adverse events). b Serious adverse reactions were reported in at least 3 patients in the POM + Low-dose Dex arm, AND at least 1% higher than the High-dose-Dex arm percentage. Data cutoff: 01 March 2013 |
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Other Adverse Reactions
Other adverse reactions of POMALYST in patients with MM, not described above, and considered important:
Cardiac Disorders: Myocardial infarction, Atrial fibrillation, Angina pectoris,
Cardiac failure congestive Ear and Labyrinth Disorders: Vertigo
Gastrointestinal disorders: Abdominal pain
General Disorders and Administration Site Conditions: General physical health deterioration, Non-cardiac chest pain, Multi-organ failure
Hepatobiliary Disorders: Hyperbilirubinemia
Infections and Infestations: Pneumocystis jiroveci pneumonia, Respiratory syncytial virus infection, Neutropenic sepsis, Bacteremia, Pneumonia respiratory syncytial viral, Cellulitis, Urosepsis, Septic shock, Clostridium difficile colitis, Pneumonia streptococcal, Lobar pneumonia, Viral infection, Lung infection
Investigations: Alanine aminotransferase increased, Hemoglobin decreased Injury, poisoning and procedural complications: Fall, Compression fracture, Spinal compression fracture
Metabolism and nutritional disorders: Hyperkalemia, Failure to thrive
Nervous system disorders: Depressed level of consciousness, Syncope
Psychiatric disorders: Mental status change Renal and urinary disorders: Urinary retention, Hyponatremia
Reproductive system and breast disorders: Pelvic pain
Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease, Pulmonary embolism, Respiratory failure, Bronchospasm
Vascular disorders: Hypotension
Kaposi Sarcoma (KS)
The safety of POMALYST in patients with KS was evaluated in Trial 12-C-0047.
Twenty-eight patients received POMALYST 5 mg taken orally once daily on Days 1 through 21 of repeated 28-day cycles. The study excluded patients with procoagulant disorders or a history of venous or arterial thromboembolism. Patients received DVT prophylaxis with daily low dose aspirin. Across all patients treated on Trial 12-C-0047, 75% were exposed to pomalidomide for 6 months or longer and 25% were exposed for greater than one year.
Serious adverse reactions occurred in 18% (5/28) of patients who received POMALYST. The following serious adverse reactions each occurred in 1 patient: anemia, decreased neutrophil count, and hematuria. Permanent discontinuation due to an adverse reaction occurred in 11% (3/28) of patients who received POMALYST.
Dosage interruptions due to an adverse reaction occurred in 14% (4/28) of patients who received POMALYST. The most frequent adverse reaction requiring dosage interruption was decreased neutrophil count, which occurred in 3 patients.
The POMALYST dose was reduced due to an adverse reaction in 1 patient due to gout.
Tables 3 and 4 summarize the adverse reactions and select laboratory abnormalities reported in Trial 12-C-0047.
Table 3: Adverse Reactions (≥ 20%) in Patients Who Received POMALYST in Trial 12-C-0047
| Adverse Reaction | Grades 1-4 N=28 % |
Grade 3 or 4 N=28 % |
| Rash, maculo-papular | 71 | 3.6 |
| Constipation | 71 | 0 |
| Fatigue | 68 | 0 |
| Nausea | 36 | 0 |
| Diarrhea | 32 | 3.6 |
| Cough | 29 | 0 |
| Dyspnea | 29 | 0 |
| Peripheral Edema | 29 | 3.6 |
| Upper respiratory tract infection | 29 | 0 |
| Muscle spasms | 25 | 0 |
| Hypothyroidism | 21 | 0 |
| Dry skin | 21 | 0 |
| Chills | 21 | 0 |
Table 4: Frequency of Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients Who Received POMALYST in Trial 12-C-0047
| Laboratory Abnormality | Grades 1-4* % | Grades 3-4* % |
| Hematology | ||
| Decreased Absolute Neutrophil Count | 96 | 50 |
| Decreased White Blood Cells | 79 | 3.6 |
| Decreased Hemoglobin | 54 | 0 |
| Decreased Platelets | 54 | 0 |
| Chemistry | ||
| Elevated Creatinine | 86 | 3.6 |
| Elevated Glucose | 57 | 7 |
| Decreased Albumin | 54 | 0 |
| Decreased Phosphate | 54 | 25 |
| Decreased Calcium | 50 | 0 |
| Increased Alanine Aminotransferase (ALT) | 32 | 0 |
| Increased Aspartate Aminotransferase (AST) | 25 | 0 |
| Elevated Creatine Kinase | 25 | 7 |
| Decreased Magnesium | 14 | 0 |
| Elevated Alkaline Phosphate | 14 | 3.6 |
| * Denominator is the number of patients for whom there is a baseline and at least one post baseline assessment for the laboratory parameter. | ||
Postmarketing Experience
The following adverse reactions have been identified during postapproval use of POMALYST. 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.
Blood and Lymphatic System Disorders: Pancytopenia
Endocrine Disorders: Hypothyroidism, hyperthyroidism
Gastrointestinal Disorders: Gastrointestinal hemorrhage
Hepatobiliary Disorders: Hepatic failure (including fatal cases), elevated liver enzymes
Immune system Disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria), solid organ transplant rejection
Infections and Infestations: Hepatitis B virus reactivation, Herpes zoster, progressive multifocal leukoencephalopathy (PML)
Neoplasms benign, malignant and unspecified (incl cysts and polyps): Tumor lysis syndrome, basal cell carcinoma, and squamous cell carcinoma of the skin
Skin and Subcutaneous Tissue Disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)
SRC: NLM .