Pomalidomide

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM See full prescribing information for complete boxed warning EMBRYO-FETAL TOXICITY • Pomalidomide capsules are contraindicated in pregnancy. Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe life-threatening birth defects ( 4 , 5.1 , 8.1 ). • For females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment by the use of 2 reliable methods of contraception ( 5.1 , 8.3 ). Pomalidomide capsules are available only through a restricted program called PS-Pomalidomide REMS ( 5.2 ). VENOUS AND ARTERIAL THROMBOEMBOLISM • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with pomalidomide capsules. Antithrombotic prophylaxis is recommended ( 5.3 ). Embryo-Fetal Toxicity • Pomalidomide capsules are contraindicated in pregnancy. Pomalidomide is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting pomalidomide treatment. • Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide treatment [see Contraindications (4) , Warnings and Precautions (5.1) and Use in Specific Populations (8.1 , 8.3) ]. Pomalidomide capsules are only available through a restricted distribution program called PS-Pomalidomide REMS [see Warnings and Precautions (5.2) ]. Information about PS-Pomalidomide REMS is available at www.PS-PomalidomideREMS.com or by calling the REMS Call Center at 1-888-423-5436. Venous and Arterial Thromboembolism • Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with pomalidomide capsules. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors [see Warnings and Precautions (5.3) ].

5 WARNINGS AND PRECAUTIONS • Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue ( 5.4 ). • Hematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia ( 5.5 ). • Hepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly ( 5.6 ). • Severe Cutaneous Reactions: Discontinue pomalidomide capsules for severe reactions ( 5.7 ). • Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions ( 5.11 ). • Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue pomalidomide capsules for angioedema and anaphylaxis ( 5.12 ). 5.1 Embryo-Fetal Toxicity Pomalidomide is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations (8.1) ] . Pomalidomide capsules are only available through PS-Pomalidomide REMS [see Warnings and Precautions (5.2) ]. Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning pomalidomide therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with pomalidomide capsules, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of pomalidomide therapy. Two negative pregnancy tests must be obtained prior to initiating therapy. The first test should be performed within 10-14 days and the second test within 24 hours prior to prescribing pomalidomide therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3) ]. Males Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking pomalidomide capsules and for up to 4 weeks after discontinuing pomalidomide capsules, even if they have undergone a successful vasectomy. Male patients taking pomalidomide capsules must not donate sperm [see Use in Specific Populations (8.3) ] . Blood Donation Patients must not donate blood during treatment with pomalidomide capsules 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 pomalidomide. 5.2 PS-Pomalidomide REMS Because of the embryo-fetal risk [see Warnings and Precautions (5.1) ] , pomalidomide capsules are available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), "PS-Pomalidomide REMS" . Required components of PS-Pomalidomide REMS include the following: • Prescribers must be certified with PS-Pomalidomide REMS by enrolling and complying with the REMS requirements. • Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ] and males must comply with contraception requirements [see Use in Specific Populations (8.3) ] . • Pharmacies must be certified with PS-Pomalidomide REMS , must only dispense to patients who are authorized to receive pomalidomide capsules and comply with REMS requirements. Further information about PS-Pomalidomide REMS is available at www.PS-PomalidomideREMS.com or by telephone at 1-888-423-5436. 5.3 Venous and Arterial Thromboembolism Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with pomalidomide. In Trial 2, where anticoagulant therapies were mandated, thromboembolic events occurred in 8% of patients treated with pomalidomide and low dose-dexamethasone (Low-dose Dex), and 3.3% of patients treated with high-dose dexamethasone. Venous thromboembolic events (VTE) occurred in 4.7% of patients treated with pomalidomide and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone. Arterial thromboembolic events include terms for arterial thromboembolic events, ischemic cerebrovascular conditions, and ischemic heart disease. Arterial thromboembolic events occurred in 3% of patients treated with pomalidomide and Low-dose Dex, and 1.3% of patients treated with high-dose dexamethasone. 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 choice of regimen should be based on assessment of the patient's underlying risk factors. 5.4 Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. 5.5 Hematologic Toxicity Multiple Myeloma In trials 1 and 2 in patients who received pomalidomide + Low-dose Dex, neutropenia was the most frequently reported Grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade 3 or 4 neutropenia was 46%. The rate of febrile neutropenia was 8%. Monitor patients for hematologic toxicities, especially neutropenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification [see Dosage and Administration (2.4) ] . 5.6 Hepatotoxicity Hepatic failure, including fatal cases, has occurred in patients treated with pomalidomide capsules. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with pomalidomide capsules. Monitor liver function tests monthly. Stop pomalidomide capsules upon elevation of liver enzymes and evaluate. After return to baseline values, treatment at a lower dose may be considered. 5.7 Severe Cutaneous Reactions Severe cutaneous reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. DRESS may present with a cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, fever, and/or lymphadenopathy with systemic complications such as hepatitis, nephritis, pneumonitis, myocarditis, and/or pericarditis. These reactions can be fatal. Consider pomalidomide capsules interruption or discontinuation for Grade 2 or 3 skin rash. Permanently discontinue pomalidomide capsules for Grade 4 rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS [see Dosage and Administration (2.5) ] . 5.8 Dizziness and Confusional State In trials 1 and 2 in patients who received pomalidomide + Low-dose Dex, 14% of patients experienced dizziness and 7% of patients experienced a confusional state; 1% of patients experienced Grade 3 or 4 dizziness, and 3% of patients experienced Grade 3 or 4 confusional state. Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice. 5.9 Neuropathy In trials 1 and 2 in patients who received pomalidomide + Low-dose Dex, 18% of patients experienced neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Two percent of patients experienced Grade 3 neuropathy in trial 2. There were no cases of Grade 4 neuropathy adverse reactions reported in either trial. 5.10 Risk of Second Primary Malignancies Cases of acute myelogenous leukemia have been reported in patients receiving pomalidomide as an investigational therapy outside of MM. 5.11 Tumor Lysis Syndrome Tumor lysis syndrome (TLS) may occur in patients treated with pomalidomide capsules. Patients at risk for TLS are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken. 5.12 Hypersensitivity Hypersensitivity, including angioedema, anaphylaxis, and anaphylactic reactions to pomalidomide have been reported. Permanently discontinue pomalidomide capsules for angioedema or anaphylaxis [see Dosage and Administration (2.5) ] .

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in detail in other labeling sections: • Embryo-Fetal Toxicity [see Warnings and Precautions (5.1 , 5.2) ] • Venous and Arterial Thromboembolism [see Warnings and Precautions (5.3) ] • Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4) ] • Hematologic Toxicity [see Warnings and Precautions (5.5)] • Hepatotoxicity [see Warnings and Precautions (5.6) ] • Severe Cutaneous Reactions [see Warnings and Precautions (5.7) ] • Dizziness and Confusional State [see Warnings and Precautions (5.8) ] • Neuropathy [see Warnings and Precautions (5.9) ] • Risk of Second Primary Malignancies [see Warnings and Precautions (5.10) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.11) ] • Hypersensitivity [see Warnings and Precautions (5.12) ] • MM: Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 pomalidomide + Low-dose Dex (112 patients) or pomalidomide 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 pomalidomide+ Low-dose Dex (300 patients) or High-dose Dexamethasone (High-dose Dex) (150 patients). The median number of treatment cycles for the pomalidomide + Low-dose Dex arm was 5. In the pomalidomide + Low-dose Dex arm, 67% of patients had a dose interruption of pomalidomide, the median time to the first dose interruption of pomalidomide was 4.1 weeks. Twenty-seven percent of patients had a dose reduction of pomalidomide, the median time to the first dose reduction of pomalidomide was 4.5 weeks. Eight percent of patients discontinued pomalidomide due to adverse reactions. Tables 3 and 4 summarize the adverse reactions reported in Trials 1 and 2, respectively. Table 3: Adverse Reactions in Any Pomalidomide Treatment Arm in Trial 1* All Adverse Reactions ≥10% in Either Arm Grade 3 or 4 ≥5% in Either Arm Body System Adverse Reaction Pomalidomide a (N=107) Pomalidomide + Low-dose Dex (N=112) Pomalidomide (N=107) Pomalidomide + 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 pomalidomide. a Pomalidomide alone arm includes all patients randomized to the pomalidomide 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 pomalidomide treatment arm. Data cutoff: 01 March 2013 Table 4: Adverse Reactions in Trial 2 a Percentage did not meet the criteria to be considered as an adverse reaction for pomalidomide 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 All Adverse Reactions (≥5% in Pomalidomide + Low-dose Dex arm, and at least 2% higher than the High-dose-Dex arm) Grade 3 or 4 (≥1% in Pomalidomide + Low-dose Dex arm, and at least 1% higher than the High-dose-Dex arm) Body System Adverse Reaction Pomalidomide + Low-dose Dex (N=300) High-dose Dex (N=150) Pomalidomide + 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) Other Adverse Reactions Other adverse reactions of pomalidomide capsules 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 6.2 Post-marketing Experience The following adverse reactions have been identified during post-approval use of pomalidomide capsules. 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)

<table ID="_RefID0EWHBG" width="90%"><caption>Table 3: Adverse Reactions in Any Pomalidomide Treatment Arm in Trial 1*</caption><col width="24%"/><col width="18%"/><col width="20%"/><col width="19%"/><col width="20%"/><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">All Adverse Reactions &#x2265;10% in Either Arm</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Grade 3 or 4 &#x2265;5% in Either Arm</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Body System</content> Adverse Reaction</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide</content>^a <content styleCode="bold"> (N=107)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide + Low-dose Dex</content> <content styleCode="bold">(N=112)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide</content> <content styleCode="bold">(N=107)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide + Low-dose Dex</content> <content styleCode="bold">(N=112)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Number (%) of patients with at least one adverse reaction</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>107 (100)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>112 (100)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>98 (92)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>102 (91)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Blood and lymphatic system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Neutropenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>57 (53)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>55 (49)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>51 (48)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>46 (41)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Anemia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>41 (38)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>47 (42)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>24 (21)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Thrombocytopenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>28 (26)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>26 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>24 (22)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>21 (19)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Leukopenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Febrile neutropenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (3)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Lymphopenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (4)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Fatigue and asthenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>62 (58)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>70 (63)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (17)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Edema peripheral</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27 (25)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pyrexia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>36 (32)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Chills</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nausea ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>39 (36)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27 (24)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Constipation ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>38 (36)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>41 (37)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Diarrhea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>37 (35)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>40 (36)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Vomiting ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Back pain ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>37 (35)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>36 (32)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Musculoskeletal chest pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Muscle spasms</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (21)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Arthralgia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Muscular weakness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Bone pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Musculoskeletal pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pain in extremity</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Infections and infestations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Upper respiratory tract infection</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>40 (37)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>32 (29)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pneumonia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>30 (28)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>38 (34)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>21 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>32 (29)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Urinary tract infection ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (9)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Sepsis ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (4)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>21 (19)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypercalcemia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (21)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypokalemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hyperglycemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hyponatremia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dehydration ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;10%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (4.7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (5.4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypocalcemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dyspnea ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>38 (36)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>50 (45)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Cough</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (22)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Epistaxis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Productive cough</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Oropharyngeal pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>24 (22)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (18)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Peripheral neuropathy</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (21)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (18)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Rash</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (21)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (16)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>&lt;5%</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pruritus</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dry skin</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hyperhidrosis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (16)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Night sweats</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Investigations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Blood creatinine increased ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (19)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (3)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Weight decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Weight increased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Psychiatric disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Anxiety</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Confusional state ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>13 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (3)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Insomnia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (16)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph><content styleCode="bold"> Renal and urinary disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> Renal failure ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>16 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (7)</paragraph></td></tr></tbody></table>

<table width="90%"><caption>Table 4: Adverse Reactions in Trial 2</caption><col width="23%"/><col width="18%"/><col width="20%"/><col width="19%"/><col width="20%"/><tfoot><tr><td align="left" colspan="5" valign="top">^a Percentage did not meet the criteria to be considered as an adverse reaction for pomalidomide 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</td></tr></tfoot><tbody><tr><td styleCode="Rrule Botrule Lrule Toprule " valign="top"/><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">All Adverse Reactions</content> <content styleCode="bold"> (&#x2265;5% in Pomalidomide + Low-dose Dex arm, and at least 2% higher than the High-dose-Dex arm)</content></paragraph></td><td align="center" colspan="2" styleCode="Rrule Botrule Toprule " valign="bottom"><paragraph><content styleCode="bold">Grade 3 or 4</content> <content styleCode="bold">(&#x2265;1% in Pomalidomide + Low-dose Dex arm, and at least 1% higher than the High-dose-Dex arm)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Body System</content> Adverse Reaction</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide + Low-dose Dex</content> <content styleCode="bold">(N=300)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">High-dose Dex</content> <content styleCode="bold">(N=150)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">Pomalidomide + Low-dose Dex</content> <content styleCode="bold"> (N=300)</content></paragraph></td><td align="center" styleCode="Rrule Botrule " valign="bottom"><paragraph><content styleCode="bold">High-dose Dex</content> <content styleCode="bold"> (N=150)</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph>Number (%) of patients with at least one adverse reaction</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>297 (99)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>149 (99)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>259 (86)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>127 (85)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Blood and lymphatic system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Neutropenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>154 (51)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31 (21)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>145 (48)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>24 (16)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Thrombocytopenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>89 (30) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>44 (29) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>66 (22) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>39 (26) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Leukopenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>38 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>27 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (3)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Febrile neutropenia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>28 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>28 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">General disorders and administration site conditions</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Fatigue and asthenia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>140 (47)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>64 (43)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>26 (9) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (12) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pyrexia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>80 (27)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>35 (23)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (3) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (5) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Edema peripheral</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>52 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (2) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (4) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Infections and infestations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Upper respiratory tract infection ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>93 (31)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pneumonia ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>58 (19)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>47 (16)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (10)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Neutropenic sepsis ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Gastrointestinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Diarrhea </paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>66 (22)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>28 (19)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Constipation</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>65 (22)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Nausea</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>45 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (11)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Vomiting</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (4)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Musculoskeletal and connective tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Back pain ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>59 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>24 (16)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (4)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Bone pain ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>54 (18)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>21 (14)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (5)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Muscle spasms</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>46 (15)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>11 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Arthralgia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>26 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pain in extremity</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>20 (7) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (6) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Respiratory, thoracic and mediastinal disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dyspnea ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>76 (25)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>25 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (5)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Cough</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>60 (20)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (10)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Chronic obstructive pulmonary disease ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Nervous system disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Peripheral neuropathy</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>52 (17)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Dizziness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>37 (12)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (9)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Headache</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Tremor</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>17 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Depressed level of consciousness</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Metabolism and nutrition disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Decreased appetite</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>38 (13)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypokalemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>28 (9) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (8) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (4)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (3)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hypocalcemia</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>12 (4) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>9 (6) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Skin and subcutaneous tissue disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Rash</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>23 (8)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Pruritus</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>22 (7)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Hyperhidrosis</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0) ^a</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Investigations</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Neutrophil count decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>15 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>14 (5)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Platelet count decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>10 (3) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> White blood cell count decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (3) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (3)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Alanine aminotransferase increased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>7 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Aspartate aminotransferase increased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>2 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Lymphocyte count decreased</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Renal and urinary disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Renal failure</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>31 (10) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>18 (12) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>19 (6)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>8 (5)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Injury, poisoning and procedural complications</content></paragraph></td></tr><tr><td styleCode="Rrule Lrule Botrule " valign="top"><paragraph> Femur fracture ^b</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>5 (2)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>1 (&lt;1)</paragraph></td></tr><tr><td colspan="5" styleCode="Rrule Lrule Botrule " valign="top"><paragraph> <content styleCode="bold">Reproductive system and breast disorders</content></paragraph></td></tr><tr><td styleCode="Rrule Botrule Lrule " valign="top"><paragraph> Pelvic pain</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>6 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>3 (2) ^a</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>4 (1)</paragraph></td><td align="center" styleCode="Rrule Botrule " valign="top"><paragraph>0 (0.0)</paragraph></td></tr></tbody></table>