ADVERSE REACTIONS SECTION.

6ADVERSE REACTIONS. The following clinically significant adverse reactions are described in detail in other labeling sections:oEmbryo-Fetal Toxicity [see Warnings and Precautions (5.1, 5.2)]oVenous and Arterial Thromboembolism [see Warnings and Precautions (5.3)]oIncreased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4)]oHematologic Toxicity [see Warnings and Precautions (5.5)] oHepatotoxicity [see Warnings and Precautions (5.6)]oSevere Cutaneous Reactions [see Warnings and Precautions (5.7)]oDizziness and Confusional State [see Warnings and Precautions (5.8)]oNeuropathy [see Warnings and Precautions (5.9)]oRisk of Second Primary Malignancies [see Warnings and Precautions (5.10)]oTumor Lysis Syndrome [see Warnings and Precautions (5.11)]oHypersensitivity [see Warnings and Precautions (5.12)]. oEmbryo-Fetal Toxicity [see Warnings and Precautions (5.1, 5.2)]. oVenous and Arterial Thromboembolism [see Warnings and Precautions (5.3)]. oIncreased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4)]. oHematologic Toxicity [see Warnings and Precautions (5.5)] oHepatotoxicity [see Warnings and Precautions (5.6)]. oSevere Cutaneous Reactions [see Warnings and Precautions (5.7)]. oDizziness and Confusional State [see Warnings and Precautions (5.8)]. oNeuropathy [see Warnings and Precautions (5.9)]. oRisk of Second Primary Malignancies [see Warnings and Precautions (5.10)]. oTumor Lysis Syndrome [see Warnings and Precautions (5.11)]. oHypersensitivity [see Warnings and Precautions (5.12)]. oMM: 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).oKS: Most common adverse reactions including laboratory abnormalities (>=30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea (6.1).To report SUSPECTED ADVERSE REACTIONS, contact Celgene Corporation at 1-888-423-5436 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.. oMM: 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).. oKS: Most common adverse reactions including laboratory abnormalities (>=30%) are decreased absolute neutrophil count or white blood cells, elevated creatinine or glucose, rash, constipation, fatigue, decreased hemoglobin, platelets, phosphate, albumin, or calcium, increased ALT, nausea, and diarrhea (6.1).. 6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 dose interruption of either drug due to adverse reactions. Forty-two percent of patients in the study had 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 dose interruption of POMALYST, the median time to the first dose interruption of POMALYST was 4.1 weeks. Twenty-seven percent of patients had 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 and summarize the adverse reactions reported in Trials and 2, respectively.Table 3: Adverse Reactions in Any POMALYST Treatment Arm in Trial Regardless of attribution of relatedness to POMALYST. 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. Serious adverse reactions were reported in at least patients in any POMALYST treatment arm.Data cutoff: 01 March 2013All Adverse Reactions >=10% in Either ArmGrade or >=5% in Either ArmBody SystemAdverse ReactionPOMALYSTa (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 reaction107 (100)112 (100)98 (92)102 (91) Blood and lymphatic system disorders Neutropenia 57 (53)55 (49)51 (48)46 (41) Anemia 41 (38)47 (42)25 (23)24 (21) Thrombocytopenia 28 (26)26 (23)24 (22)21 (19) Leukopenia14 (13)22 (20)7 (7)11 (10) Febrile neutropenia <10%<10%6 (6)3 (3) Lymphopenia4 (4)17 (15)2 (2)8 (7) General disorders and administration site conditions Fatigue and asthenia 62 (58)70 (63)13 (12)19 (17) Edema peripheral27 (25)19 (17)0 (0.0)0 (0.0) Pyrexia 25 (23)36 (32)<5%<5% Chills11 (10)14 (13)0 (0.0)0 (0.0) Gastrointestinal disorders Nausea 39 (36)27 (24)<5%<5% Constipation 38 (36)41 (37)<5%<5% Diarrhea37 (35)40 (36)<5%<5% Vomiting 15 (14)16 (14)<5%0 (0.0) Musculoskeletal and connective tissue disorders Back pain 37 (35)36 (32)15 (14)11 (10) Musculoskeletal chest pain25 (23)22 (20)<5%0 (0.0) Muscle spasms23 (21)22 (20)<5%<5% Arthralgia18 (17)17 (15)<5%<5% Muscular weakness15 (14)15 (13)6 (6)4 (4) Bone pain13 (12)8 (7)<5%<5% Musculoskeletal pain13 (12)19 (17)<5%<5% Pain in extremity8 (7)16 (14)0 (0.0)<5% Infections and infestations Upper respiratory tract infection40 (37)32 (29)<5%<5% Pneumonia 30 (28)38 (34)21 (20)32 (29) Urinary tract infection 11 (10)19 (17)2 (2)10 (9) Sepsis <10%<10%6 (6)5 (4) Metabolism and nutrition disorders Decreased appetite25 (23)21 (19)<5%0 (0.0) Hypercalcemia 23 (21)13 (12)11 (10)1 (<1) Hypokalemia13 (12)13 (12)<5%<5% Hyperglycemia12 (11)17 (15)<5%<5% Hyponatremia12 (11)14 (13)<5%<5% Dehydration <10%<10%5 (4.7)6 (5.4) Hypocalcemia6 (6)13 (12)0 (0.0)<5% Respiratory, thoracic and mediastinal disorders Dyspnea 38 (36)50 (45)8 (7)14 (13) Cough18 (17)25 (22)0 (0.0)0 (0.0) Epistaxis18 (17)12 (11)<5%0 (0.0) Productive cough10 (9)14 (13)0 (0.0)0 (0.0) Oropharyngeal pain6 (6)12 (11)0 (0.0)0 (0.0) Nervous system disorders Dizziness24 (22)20 (18)<5%<5% Peripheral neuropathy23 (21)20 (18)0 (0.0)0 (0.0) Headache16 (15)15 (13)0 (0.0)<5% Tremor11 (10)15 (13)0 (0.0)0 (0.0) Skin and subcutaneous tissue disorders Rash22 (21)18 (16)0 (0.0)<5% Pruritus16 (15)10 (9)0 (0.0)0 (0.0) Dry skin10 (9)12 (11)0 (0.0)0 (0.0) Hyperhidrosis8 (7)18 (16)0 (0.0)0 (0.0) Night sweats5 (5)14 (13)0 (0.0)0 (0.0) Investigations Blood creatinine increased 20 (19)11 (10)6 (6)3 (3) Weight decreased16 (15)10 (9)0 (0.0)0 (0.0) Weight increased1 (<1)12 (11)0 (0.0)0 (0.0) Psychiatric disorders Anxiety14 (13)8 (7)0 (0.0)0 (0.0) Confusional state 13 (12)15 (13)6 (6)3 (3) Insomnia7 (7)18 (16)0 (0.0)0 (0.0) Renal and urinary disorders Renal failure 16 (15)11 (10)9 (8)8 (7)Table 4: Adverse Reactions in Trial 2a Serious adverse reactions were reported in at least patients in the POM Low-dose Dex arm, AND at least 1% higher than the High-dose-Dex arm percentage. 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 or adverse events).Data cutoff: 01 March 2013All Adverse Reactions (>=5% in POMALYST Low-dose Dex arm, and at least 2% higher than the High-dose-Dex arm)Grade or 4(>=1% in POMALYST Low-dose Dex arm, and at least 1% higher than the High-dose-Dex arm)Body SystemAdverse ReactionPOMALYST 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 reaction297 (99)149 (99)259 (86)127 (85) Blood and lymphatic system disorders Neutropenia 154 (51)31 (21)145 (48)24 (16) Thrombocytopenia89 (30) 44 (29) 66 (22) 39 (26) Leukopenia38 (13)8 (5)27 (9)5 (3) Febrile neutropenia 28 (9)0 (0.0)28 (9)0 (0.0) General disorders and administration site conditions Fatigue and asthenia140 (47)64 (43)26 (9) 18 (12) Pyrexia 80 (27)35 (23)9 (3) 7 (5) Edema peripheral52 (17)17 (11)4 (1) 3 (2) Pain11 (4) 3 (2) 5 (2)1 (<1) Infections and infestations Upper respiratory tract infection 93 (31)19 (13)9 (3)1 (<1) Pneumonia 58 (19)20 (13)47 (16)15 (10) Neutropenic sepsis 3 (1) 0 (0.0) 3 (1)0 (0.0) Gastrointestinal disorders Diarrhea 66 (22)28 (19)3 (1) 2 (1) Constipation65 (22)22 (15)7 (2)0 (0.0) Nausea45 (15)17 (11)3 (1) 2 (1) Vomiting23 (8)6 (4)3 (1)0 (0.0) Musculoskeletal and connective tissue disorders Back pain 59 (20)24 (16)15 (5)6 (4) Bone pain 54 (18)21 (14)22 (7)7 (5) Muscle spasms46 (15)11 (7)1 (<1) 1 (<1) Arthralgia26 (9)7 (5)2 (<1) 1 (<1) Pain in extremity20 (7) 9 (6) 6 (2)0 (0.0) Respiratory, thoracic and mediastinal disorders Dyspnea 76 (25)25 (17)17 (6)7 (5) Cough60 (20)15 (10)2 (<1) 1 (<1) Chronic obstructive pulmonary disease 5 (2) 0 (0.0) 4 (1)0 (0.0) Nervous system disorders Peripheral neuropathy52 (17)18 (12)5 (2) 2 (1) Dizziness37 (12)14 (9)4 (1) 2 (1) Headache23 (8)8 (5)1 (<1) 0 (0.0) Tremor17 (6)2 (1)2 (<1) 0 (0.0) Depressed level of consciousness5 (2) 0 (0.0) 3 (1)0 (0.0) Metabolism and nutrition disorders Decreased appetite38 (13)12 (8)3 (1) 2 (1) Hypokalemia28 (9) 12 (8) 12 (4)4 (3) Hypocalcemia12 (4) 9 (6) 5 (2)1 (<1) Skin and subcutaneous tissue disorders Rash23 (8)2 (1)3 (1)0 (0.0) Pruritus22 (7)5 (3)0 (0.0) 0 (0.0) Hyperhidrosis15 (5)1 (<1)0 (0.0) 0 (0.0) Investigations Neutrophil count decreased15 (5)1 (<1)14 (5)1 (<1) Platelet count decreased10 (3) 3 (2) 8 (3)2 (1) White blood cell count decreased8 (3) 1 (<1) 8 (3)0 (0.0) Alanine aminotransferase increased7 (2) 2 (1) 5 (2)0 (0.0) Aspartate aminotransferase increased4 (1) 2 (1) 3 (1)0 (0.0) Lymphocyte count decreased3 (1) 1 (<1) 3 (1)0 (0.0) Renal and urinary disorders Renal failure31 (10) 18 (12) 19 (6)8 (5) Injury, poisoning and procedural complications Femur fracture 5 (2) 1 (<1) 5 (2)1 (<1) Reproductive system and breast disorders Pelvic pain6 (2) 3 (2) 4 (1)0 (0.0). Other Adverse ReactionsOther adverse reactions of POMALYST in patients with MM, not described above, and considered important:Cardiac Disorders: Myocardial infarction, Atrial fibrillation, Angina pectoris, Cardiac failure congestiveEar and Labyrinth Disorders: VertigoGastrointestinal disorders: Abdominal painGeneral Disorders and Administration Site Conditions: General physical health deterioration, Non-cardiac chest pain, Multi-organ failureHepatobiliary Disorders: HyperbilirubinemiaInfections 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 infectionInvestigations: Alanine aminotransferase increased, Hemoglobin decreasedInjury, poisoning and procedural complications: Fall, Compression fracture, Spinal compression fractureMetabolism and nutritional disorders: Hyperkalemia, Failure to thriveNervous system disorders: Depressed level of consciousness, SyncopePsychiatric disorders: Mental status changeRenal and urinary disorders: Urinary retention, HyponatremiaReproductive system and breast disorders: Pelvic painRespiratory, thoracic, and mediastinal disorders: Interstitial lung disease, Pulmonary embolism, Respiratory failure, BronchospasmVascular disorders: Hypotension. Kaposi Sarcoma (KS)The safety of POMALYST in patients with KS was evaluated in Trial 12-C-0047 [see Clinical Studies (14.2)]. Twenty-eight patients received POMALYST mg taken orally once daily on Days through 21 of repeated 28-day cycles. The study excluded patients with procoagulant disorders or 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 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 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 patients.The POMALYST dose was reduced due to an adverse reaction in patient due to gout.Tables and summarize the adverse reactions and select laboratory abnormalities reported in Trial 12-C-0047.Table 5: Adverse Reactions (>= 20%) in Patients Who Received POMALYST in Trial 12-C-0047Adverse ReactionGrades 1-4N=28%Grade or 4N=28%Rash, maculo-papular713.6Constipation710Fatigue680Nausea360Diarrhea323.6Cough290Dyspnea290Peripheral Edema293.6Upper respiratory tract infection290Muscle spasms250Hypothyroidism210Dry skin210Chills210Table 6: Frequency of Select Laboratory Abnormalities (>= 10%) Worsening from Baseline in Patients Who Received POMALYST in Trial 12-C-0047 Denominator is the number of patients for whom there is baseline and at least one post baseline assessment for the laboratory parameter.Laboratory AbnormalityGrades 1-4%Grades 3-4%HematologyDecreased Absolute Neutrophil Count9650Decreased White Blood Cells793.6Decreased Hemoglobin540Decreased Platelets540ChemistryElevated Creatinine863.6Elevated Glucose577Decreased Albumin540Decreased Phosphate5425Decreased Calcium500Increased Alanine Aminotransferase (ALT)320Increased Aspartate Aminotransferase (AST)250Elevated Creatine Kinase257Decreased Magnesium140Elevated Alkaline Phosphate143.6. 6.2Postmarketing Experience. The following adverse reactions have been identified during postapproval use of POMALYST. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Blood and Lymphatic System Disorders: PancytopeniaEndocrine Disorders: Hypothyroidism, hyperthyroidismGastrointestinal Disorders: Gastrointestinal hemorrhageHepatobiliary Disorders: Hepatic failure (including fatal cases), elevated liver enzymesImmune system Disorders: Allergic reactions (e.g., angioedema, anaphylaxis, urticaria), solid organ transplant rejectionInfections and Infestations: Hepatitis 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 skinSkin and Subcutaneous Tissue Disorders: Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS).

HEPATIC IMPAIRMENT SUBSECTION.

8.7Hepatic Impairment. Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment [see Dosage and Administration (2.8) and Clinical Pharmacology (12.3)].

HOW SUPPLIED SECTION.

16HOW SUPPLIED/STORAGE AND HANDLING. Dark blue opaque cap and yellow opaque body, imprinted POML on the cap in white ink and 1 mg on the body in black ink1 mg bottles of 21(NDC 59572-501-21)1 mg bottles of 100(NDC 59572-501-00)Dark blue opaque cap and orange opaque body, imprinted POML on the cap and 2 mg on the body in white ink2 mg bottles of 21(NDC 59572-502-21)2 mg bottles of 100(NDC 59572-502-00)Dark blue opaque cap and green opaque body, imprinted POML on the cap and 3 mg on the body in white ink3 mg bottles of 21(NDC 59572-503-21)3 mg bottles of 100(NDC 59572-503-00)Dark blue opaque cap and blue opaque body, imprinted POML on the cap and 4 mg on the body in white ink4 mg bottles of 21(NDC 59572-504-21)4 mg bottles of 100(NDC 59572-504-00). Store at 20C-25C (68F-77F); excursions permitted to 15C-30C (59F-86F) [see USP Controlled Room Temperature].Care should be exercised in handling of POMALYST. Do not open or crush POMALYST capsules. If powder from POMALYST contacts the skin, wash the skin immediately and thoroughly with soap and water. If POMALYST contacts the mucous membranes, flush thoroughly with water.Follow procedures for proper handling and disposal of hazardous drugs.

INDICATIONS & USAGE SECTION.

1INDICATIONS AND USAGE. POMALYST is thalidomide analogue indicated, for the treatment of adult patients:oin combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy (1.1).owith AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s) (1.2).. oin combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy (1.1).. owith AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s) (1.2).. 1.1Multiple Myeloma. POMALYST, in combination with dexamethasone, is indicated for adult patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.. 1.2Kaposi Sarcoma. POMALYST is indicated for the treatment of:oAdult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART).oKaposi sarcoma (KS) in adult patients who are HIV-negative.This indication is approved under accelerated approval based on overall response rate [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).. oAdult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART).. oKaposi sarcoma (KS) in adult patients who are HIV-negative.

INFORMATION FOR PATIENTS SECTION.

17PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Medication Guide).. Embryo-Fetal ToxicityAdvise patients that POMALYST is contraindicated in pregnancy [see Contraindications (4)]. POMALYST is thalidomide analogue and may cause serious birth defects or death to developing baby [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].oAdvise females of reproductive potential that they must avoid pregnancy while taking POMALYST and for at least weeks after completing therapy.oInitiate POMALYST treatment in females of reproductive potential only following negative pregnancy test.oAdvise females of reproductive potential of the importance of monthly pregnancy tests and the need to use different forms of contraception, including at least highly effective form, simultaneously during POMALYST therapy, during dose interruptions, and for weeks after she has completely finished taking POMALYST. Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch, or implants) and partners vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap.oInstruct patient to immediately stop taking POMALYST and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant.oAdvise patient that if her healthcare provider is not available, she should call Celgene Customer Care Center at 1-888-423-5436 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].oAdvise males to always use latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to weeks after discontinuing POMALYST, even if they have undergone successful vasectomy.oAdvise male patients taking POMALYST that they must not donate sperm [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].oAll patients must be instructed to not donate blood while taking POMALYST and for weeks following discontinuation of POMALYST [see Warnings and Precautions (5.1)].. oAdvise females of reproductive potential that they must avoid pregnancy while taking POMALYST and for at least weeks after completing therapy.. oInitiate POMALYST treatment in females of reproductive potential only following negative pregnancy test.. oAdvise females of reproductive potential of the importance of monthly pregnancy tests and the need to use different forms of contraception, including at least highly effective form, simultaneously during POMALYST therapy, during dose interruptions, and for weeks after she has completely finished taking POMALYST. Highly effective forms of contraception other than tubal ligation include IUD and hormonal (birth control pills, injections, patch, or implants) and partners vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap.. oInstruct patient to immediately stop taking POMALYST and contact her healthcare provider if she becomes pregnant while taking this drug, if she misses her menstrual period or experiences unusual menstrual bleeding, if she stops taking birth control, or if she thinks FOR ANY REASON that she may be pregnant.. oAdvise patient that if her healthcare provider is not available, she should call Celgene Customer Care Center at 1-888-423-5436 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].. oAdvise males to always use latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to weeks after discontinuing POMALYST, even if they have undergone successful vasectomy.. oAdvise male patients taking POMALYST that they must not donate sperm [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].. oAll patients must be instructed to not donate blood while taking POMALYST and for weeks following discontinuation of POMALYST [see Warnings and Precautions (5.1)].. POMALYST REMS ProgramBecause of the risk of embryo-fetal toxicity, POMALYST is only available through restricted program called POMALYST REMS [see Warnings and Precautions (5.2)].oPatients must sign Patient-Physician Agreement Form and comply with the requirements to receive POMALYST. In particular, females of reproductive potential must comply with the pregnancy testing, contraception requirements, and participate in monthly telephone surveys. Males must comply with the contraception requirements [see Use in Specific Populations (8.3)].oPOMALYST is available only from pharmacies that are certified in POMALYST REMS program. Provide patients with the telephone number and website for information on how to obtain the product.. oPatients must sign Patient-Physician Agreement Form and comply with the requirements to receive POMALYST. In particular, females of reproductive potential must comply with the pregnancy testing, contraception requirements, and participate in monthly telephone surveys. Males must comply with the contraception requirements [see Use in Specific Populations (8.3)].. oPOMALYST is available only from pharmacies that are certified in POMALYST REMS program. Provide patients with the telephone number and website for information on how to obtain the product.. Pregnancy Exposure RegistryInform females that there is Pregnancy Exposure Registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy and that they can contact the Pregnancy Exposure Registry by calling 1-888-423-5436 [see Use in Specific Populations (8.1)].. Venous and Arterial ThromboembolismInform patients of the risk of developing DVT, PE, MI, and stroke and to report immediately any signs and symptoms suggestive of these events for evaluation [see Warnings and Precautions (5.3)].. Hematologic ToxicitiesInform patients on the risks of developing neutropenia, thrombocytopenia, and anemia and the need to report signs and symptoms associated with these events to their healthcare provider for further evaluation [see Warnings and Precautions (5.5)].. HepatotoxicityInform patients on the risks of developing hepatotoxicity, including hepatic failure and death, and to report signs and symptoms associated with these events to their healthcare provider for evaluation [see Warnings and Precautions (5.6)].. Severe Cutaneous ReactionsInform patients of the potential risk for severe skin reactions such as SJS, TEN and DRESS and to report any signs and symptoms associated with these reactions to their healthcare provider for evaluation [see Warnings and Precautions (5.7)].. Dizziness and Confusional StateInform patients of the potential risk of dizziness and confusional state with the drug, to avoid situations where dizziness or confusional state may be problem, and not to take other medications that may cause dizziness or confusional state without adequate medical advice [see Warnings and Precautions (5.8)].. NeuropathyInform patients of the risk of neuropathy and to report the signs and symptoms associated with these events to their healthcare provider for further evaluation [see Warnings and Precautions (5.9)].. Second Primary MalignanciesInform the patient that the potential risk of developing acute myelogenous leukemia during treatment with POMALYST is unknown [see Warnings and Precautions (5.10)].. Tumor Lysis SyndromeInform patients of the potential risk of tumor lysis syndrome and to report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions (5.11)].. HypersensitivityInform patients of the potential for severe hypersensitivity reactions such as angioedema and anaphylaxis to POMALYST. Instruct patients to contact their healthcare provider right away for any signs and symptoms of these reactions. Advise patients to seek emergency medical attention for signs or symptoms of severe hypersensitivity reactions [see Warnings and Precautions (5.12)].. Smoking TobaccoAdvise patients that smoking tobacco may reduce the efficacy of POMALYST [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3)].. Dosing InstructionsInform patients on how to take POMALYST [see Dosage and Administration (2.2, 2.3, 2.9)] oPOMALYST should be taken once daily at about the same time each day.oPatients on hemodialysis should take POMALYST following hemodialysis, on hemodialysis days.oPOMALYST may be taken with or without food.oThe capsules should not be opened, broken, or chewed. POMALYST should be swallowed whole with water.oInstruct patients that if they miss dose of POMALYST, they may still take it up to 12 hours after the time they would normally take it. If more than 12 hours have elapsed, they should be instructed to skip the dose for that day. The next day, they should take POMALYST at the usual time. Warn patients not to take doses to make up for the one that they missed.. oPOMALYST should be taken once daily at about the same time each day.. oPatients on hemodialysis should take POMALYST following hemodialysis, on hemodialysis days.. oPOMALYST may be taken with or without food.. oThe capsules should not be opened, broken, or chewed. POMALYST should be swallowed whole with water.. oInstruct patients that if they miss dose of POMALYST, they may still take it up to 12 hours after the time they would normally take it. If more than 12 hours have elapsed, they should be instructed to skip the dose for that day. The next day, they should take POMALYST at the usual time. Warn patients not to take doses to make up for the one that they missed.

LACTATION SECTION.

8.2Lactation. Risk SummaryThere is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats (see Data). Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed child from POMALYST, advise women not to breastfeed during treatment with POMALYST.. Data. Animal DataFollowing single oral administration of pomalidomide to lactating rats approximately 14 days postpartum, pomalidomide was transferred into milk, with milk to plasma ratios of 0.63 to 1.46.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Pomalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of pomalidomide are mediated through its target cereblon, component of cullin ring E3 ubiquitin ligase enzyme complex. In vitro, in the presence of drug, substrate proteins (including Aiolos and Ikaros) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma (MM) cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis. Pomalidomide enhanced cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., TNF- and IL-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in mouse tumor model and in the in vitro umbilical cord model.

NONCLINICAL TOXICOLOGY SECTION.

13NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies examining the carcinogenic potential of pomalidomide have not been conducted. One of 12 monkeys dosed with mg/kg of pomalidomide (an exposure approximately 15-fold of the exposure in patients at the recommended dose of mg/day) developed acute myeloid leukemia in 9-month repeat-dose toxicology study.Pomalidomide was not mutagenic or clastogenic in battery of tests, including the bacteria reverse mutation assay (Ames test), the in vitro assay using human peripheral blood lymphocytes, and the micronucleus test in orally treated rats administered doses up to 2000 mg/kg/day.In fertility and early embryonic development study in rats, drug-treated males were mated with untreated or treated females. Pomalidomide was administered to males and females at doses of 25 to 1000 mg/kg/day. When treated males were mated with treated females, there was an increase in post-implantation loss and decrease in mean number of viable embryos at all dose levels. There were no other effects on reproductive functions or the number of pregnancies. The lowest dose tested in animals resulted in an exposure (AUC) approximately 100-fold of the exposure in patients at the recommended dose of mg/day. When treated males in this study were mated with untreated females, all uterine parameters were comparable to the controls. Based on these results, the observed effects were attributed to the treatment of females.

OVERDOSAGE SECTION.

10OVERDOSAGE. Hemodialysis can remove pomalidomide from circulation.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Pomalyst(R) (pomalidomide) Capsules, mg 21 Count Bottle Label. Pomalyst (pomalidomide) Capsules, mg 21 Count Bottle Label.

PEDIATRIC USE SECTION.

8.4Pediatric Use. The safety and effectiveness of POMALYST have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: dose escalation study in 25 pediatric patients aged to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and parallel-group study conducted in 47 pediatric patients aged to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies.At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged to 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS [see Clinical Pharmacology (12.3)].

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Pomalidomide exposure-response analyses showed that there was no relationship between systemic pomalidomide exposure level and efficacy or safety following pomalidomide dose of mg.. Cardiac ElectrophysiologyThe QTc prolongation potential of pomalidomide was evaluated in single center, randomized, double-blind crossover study (N=72) using mg pomalidomide, 20 mg pomalidomide, placebo, and 400 mg moxifloxacin (positive control). No significant QTc prolongation effect of pomalidomide was observed following pomalidomide doses of and 20 mg.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. In patients with MM who received POMALYST mg daily alone or in combination with dexamethasone, pomalidomide steady-state drug exposure was characterized by AUC (CV%) of 860 (37%) ngh/mL and Cmax (CV%) of 75 (32%) ng/mL. In patients with Kaposi sarcoma (KS) who received POMALYST mg daily, pomalidomide steady-state drug exposure was characterized by AUC of 462.3 ngh/mL (82%) and Cmax of 53.1 ng/mL (50%).. AbsorptionFollowing administration of single oral doses of POMALYST, the maximum plasma concentration (Cmax) for pomalidomide occurs at to hours postdose in patients with MM or KS.. Effect of FoodCo-administration of POMALYST with high-fat meal (approximately 50% of the total caloric content) and high-calorie meal (approximately 800 to 1000 calories) (the meal contained approximately 150, 250, and 500 to 600 calories from protein, carbohydrates, and fat, respectively) delays the Tmax by 2.5 hours, decreased mean plasma Cmax and AUC in healthy subjects by about 27% and 8%, respectively.. DistributionPomalidomide has mean apparent volume of distribution (Vd/F) between 62 and 138 at steady state in patients with MM or KS.Pomalidomide is distributed in semen of healthy subjects at concentration of approximately 67% of plasma level at hours postdose (~Tmax) after days of mg once-daily dosing.Human plasma protein binding of pomalidomide ranges from 12% to 44% and is not concentration dependent. Pomalidomide is substrate for P-gp.. EliminationPomalidomide has mean total body clearance (CL/F) of 7-10 L/h in patients with MM or KS. Pomalidomide is eliminated with median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.. MetabolismPomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. Minor contributions from CYP2C19 and CYP2D6 were also observed in vitro.. ExcretionFollowing single oral administration of [14C]-pomalidomide to healthy subjects, approximately 73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with approximately 2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.. Specific PopulationsAge (61 to 85 years old), sex and race have no clinically significant effect on the systemic exposure of pomalidomide.. Patients with Renal ImpairmentPomalidomide pharmacokinetic parameters were not significantly affected in patients with moderate (30 mL/min <= CLcr< 60 mL/min) or severe (15 mL/min <= CLcr< 30 mL/min) renal impairment relative to patients with normal renal function (CLcr >= 60 mL/min). Mean exposure (AUC) to pomalidomide increased by 38% in patients with severe renal impairment requiring dialysis (CLcr< 30 mL/min requiring dialysis) and 40% in patients with end stage renal disease (CLcr< 15 mL/min) on non-dialysis days. In patients with severe renal impairment requiring dialysis, the estimated dialysis clearance is approximately 12 L/h which is higher than pomalidomide total body clearance, indicating hemodialysis will remove pomalidomide from the blood circulation.. Patients with Hepatic ImpairmentMean exposure (AUC) of pomalidomide increased by 51%, 58% and 72% in subjects with mild, moderate or severe hepatic impairment as defined by Child-Pugh criteria, respectively.. Drug Interaction Studies. Clinical StudiesCo-administration of POMALYST with the following drugs did not increase pomalidomide exposure to clinically significant extent: ketoconazole (a strong CYP3A4 and P-gp inhibitor), carbamazepine (a strong CYP3A4 inducer) and dexamethasone (a weak to moderate CYP3A4 inducer). Co-administration of POMALYST with drugs that are CYP1A2 inducers has not been studied.. CYP1A2 Inhibitors: Co-administration of fluvoxamine (a strong CYP1A2 inhibitor) with POMALYST increased mean [90% confidence interval] pomalidomide exposure by 125% [98% to 157%] compared to POMALYST alone in healthy subjects. Co-administration of fluvoxamine in the presence of ketoconazole (a strong CYP3A4 and P-gp inhibitor) with POMALYST increased mean pomalidomide exposure by 146% [126% to 167%] compared to POMALYST administered alone in healthy subjects, indicating the predominant effect of CYP1A2 inhibition in the increase of pomalidomide exposure [see Dosage and Administration (2.6) and Drug Interactions (7.1)].. Strong CYP3A4 and P-gp Inhibitors: Co-administration of ketoconazole (a strong CYP3A4 and P-gp inhibitor) in 16 healthy male subjects increased AUC of pomalidomide by 19% compared to POMALYST administered alone.. Strong CYP1A2 Inducers: Co-administration of POMALYST with drugs that are CYP1A2 inducers has not been studied and may reduce pomalidomide exposure.. Strong CYP3A4 Inducers: Co-administration of carbamazepine to 16 healthy male subjects decreased AUC of pomalidomide by 20% with 90% confidence interval [13% to 27%] compared to when pomalidomide was administered alone.. Dexamethasone: Co-administration of multiple doses of mg POMALYST with 20 mg to 40 mg dexamethasone (a weak to moderate inducer of CYP3A4) to patients with MM had no effect on the pharmacokinetics of pomalidomide compared to when pomalidomide was administered alone.. Smoking: In 14 healthy male subjects who smoked 25 cigarettes per day for total of 10 days, after single oral dose of mg POMALYST, Cmax of pomalidomide increased 14% while AUC of pomalidomide decreased 32%, compared to that in 13 healthy male subjects who were non-smokers.. In Vitro StudiesPomalidomide does not inhibit or induce cytochrome p450 enzymes or transporters in vitro.

BOXED WARNING SECTION.

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM. WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISMSee full prescribing information for complete boxed warningEMBRYO-FETAL TOXICITYoPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe life-threatening birth defects (4, 5.1, 8.1).oFor females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment by the use of reliable methods of contraception (5.1, 8.3).POMALYST is available only through restricted program called POMALYST REMS(R) (5.2).VENOUS AND ARTERIAL THROMBOEMBOLISMoDeep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Antithrombotic prophylaxis is recommended (5.3).. oPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe life-threatening birth defects (4, 5.1, 8.1).. oFor females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment by the use of reliable methods of contraception (5.1, 8.3).. oDeep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Antithrombotic prophylaxis is recommended (5.3).. Embryo-Fetal ToxicityoPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain negative pregnancy tests before starting POMALYST treatment.oFemales of reproductive potential must use forms of contraception or continuously abstain from heterosexual sex during and for weeks after stopping POMALYST treatment [see Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. POMALYST is only available through restricted distribution program called POMALYST REMS [see Warnings and Precautions (5.2)]. oPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain negative pregnancy tests before starting POMALYST treatment.. oFemales of reproductive potential must use forms of contraception or continuously abstain from heterosexual sex during and for weeks after stopping POMALYST treatment [see Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. Venous and Arterial ThromboembolismoDeep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patients underlying risk factors [see Warnings and Precautions (5.3)]. oDeep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patients underlying risk factors [see Warnings and Precautions (5.3)].

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. Studies examining the carcinogenic potential of pomalidomide have not been conducted. One of 12 monkeys dosed with mg/kg of pomalidomide (an exposure approximately 15-fold of the exposure in patients at the recommended dose of mg/day) developed acute myeloid leukemia in 9-month repeat-dose toxicology study.Pomalidomide was not mutagenic or clastogenic in battery of tests, including the bacteria reverse mutation assay (Ames test), the in vitro assay using human peripheral blood lymphocytes, and the micronucleus test in orally treated rats administered doses up to 2000 mg/kg/day.In fertility and early embryonic development study in rats, drug-treated males were mated with untreated or treated females. Pomalidomide was administered to males and females at doses of 25 to 1000 mg/kg/day. When treated males were mated with treated females, there was an increase in post-implantation loss and decrease in mean number of viable embryos at all dose levels. There were no other effects on reproductive functions or the number of pregnancies. The lowest dose tested in animals resulted in an exposure (AUC) approximately 100-fold of the exposure in patients at the recommended dose of mg/day. When treated males in this study were mated with untreated females, all uterine parameters were comparable to the controls. Based on these results, the observed effects were attributed to the treatment of females.

CLINICAL PHARMACOLOGY SECTION.

12CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Pomalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of pomalidomide are mediated through its target cereblon, component of cullin ring E3 ubiquitin ligase enzyme complex. In vitro, in the presence of drug, substrate proteins (including Aiolos and Ikaros) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma (MM) cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis. Pomalidomide enhanced cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., TNF- and IL-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in mouse tumor model and in the in vitro umbilical cord model.. 12.2 Pharmacodynamics. Pomalidomide exposure-response analyses showed that there was no relationship between systemic pomalidomide exposure level and efficacy or safety following pomalidomide dose of mg.. Cardiac ElectrophysiologyThe QTc prolongation potential of pomalidomide was evaluated in single center, randomized, double-blind crossover study (N=72) using mg pomalidomide, 20 mg pomalidomide, placebo, and 400 mg moxifloxacin (positive control). No significant QTc prolongation effect of pomalidomide was observed following pomalidomide doses of and 20 mg.. 12.3 Pharmacokinetics. In patients with MM who received POMALYST mg daily alone or in combination with dexamethasone, pomalidomide steady-state drug exposure was characterized by AUC (CV%) of 860 (37%) ngh/mL and Cmax (CV%) of 75 (32%) ng/mL. In patients with Kaposi sarcoma (KS) who received POMALYST mg daily, pomalidomide steady-state drug exposure was characterized by AUC of 462.3 ngh/mL (82%) and Cmax of 53.1 ng/mL (50%).. AbsorptionFollowing administration of single oral doses of POMALYST, the maximum plasma concentration (Cmax) for pomalidomide occurs at to hours postdose in patients with MM or KS.. Effect of FoodCo-administration of POMALYST with high-fat meal (approximately 50% of the total caloric content) and high-calorie meal (approximately 800 to 1000 calories) (the meal contained approximately 150, 250, and 500 to 600 calories from protein, carbohydrates, and fat, respectively) delays the Tmax by 2.5 hours, decreased mean plasma Cmax and AUC in healthy subjects by about 27% and 8%, respectively.. DistributionPomalidomide has mean apparent volume of distribution (Vd/F) between 62 and 138 at steady state in patients with MM or KS.Pomalidomide is distributed in semen of healthy subjects at concentration of approximately 67% of plasma level at hours postdose (~Tmax) after days of mg once-daily dosing.Human plasma protein binding of pomalidomide ranges from 12% to 44% and is not concentration dependent. Pomalidomide is substrate for P-gp.. EliminationPomalidomide has mean total body clearance (CL/F) of 7-10 L/h in patients with MM or KS. Pomalidomide is eliminated with median plasma half-life of 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.. MetabolismPomalidomide is primarily metabolized in the liver by CYP1A2 and CYP3A4. Minor contributions from CYP2C19 and CYP2D6 were also observed in vitro.. ExcretionFollowing single oral administration of [14C]-pomalidomide to healthy subjects, approximately 73% and 15% of the radioactive dose was eliminated in urine and feces, respectively, with approximately 2% and 8% of the radiolabeled dose eliminated unchanged as pomalidomide in urine and feces.. Specific PopulationsAge (61 to 85 years old), sex and race have no clinically significant effect on the systemic exposure of pomalidomide.. Patients with Renal ImpairmentPomalidomide pharmacokinetic parameters were not significantly affected in patients with moderate (30 mL/min <= CLcr< 60 mL/min) or severe (15 mL/min <= CLcr< 30 mL/min) renal impairment relative to patients with normal renal function (CLcr >= 60 mL/min). Mean exposure (AUC) to pomalidomide increased by 38% in patients with severe renal impairment requiring dialysis (CLcr< 30 mL/min requiring dialysis) and 40% in patients with end stage renal disease (CLcr< 15 mL/min) on non-dialysis days. In patients with severe renal impairment requiring dialysis, the estimated dialysis clearance is approximately 12 L/h which is higher than pomalidomide total body clearance, indicating hemodialysis will remove pomalidomide from the blood circulation.. Patients with Hepatic ImpairmentMean exposure (AUC) of pomalidomide increased by 51%, 58% and 72% in subjects with mild, moderate or severe hepatic impairment as defined by Child-Pugh criteria, respectively.. Drug Interaction Studies. Clinical StudiesCo-administration of POMALYST with the following drugs did not increase pomalidomide exposure to clinically significant extent: ketoconazole (a strong CYP3A4 and P-gp inhibitor), carbamazepine (a strong CYP3A4 inducer) and dexamethasone (a weak to moderate CYP3A4 inducer). Co-administration of POMALYST with drugs that are CYP1A2 inducers has not been studied.. CYP1A2 Inhibitors: Co-administration of fluvoxamine (a strong CYP1A2 inhibitor) with POMALYST increased mean [90% confidence interval] pomalidomide exposure by 125% [98% to 157%] compared to POMALYST alone in healthy subjects. Co-administration of fluvoxamine in the presence of ketoconazole (a strong CYP3A4 and P-gp inhibitor) with POMALYST increased mean pomalidomide exposure by 146% [126% to 167%] compared to POMALYST administered alone in healthy subjects, indicating the predominant effect of CYP1A2 inhibition in the increase of pomalidomide exposure [see Dosage and Administration (2.6) and Drug Interactions (7.1)].. Strong CYP3A4 and P-gp Inhibitors: Co-administration of ketoconazole (a strong CYP3A4 and P-gp inhibitor) in 16 healthy male subjects increased AUC of pomalidomide by 19% compared to POMALYST administered alone.. Strong CYP1A2 Inducers: Co-administration of POMALYST with drugs that are CYP1A2 inducers has not been studied and may reduce pomalidomide exposure.. Strong CYP3A4 Inducers: Co-administration of carbamazepine to 16 healthy male subjects decreased AUC of pomalidomide by 20% with 90% confidence interval [13% to 27%] compared to when pomalidomide was administered alone.. Dexamethasone: Co-administration of multiple doses of mg POMALYST with 20 mg to 40 mg dexamethasone (a weak to moderate inducer of CYP3A4) to patients with MM had no effect on the pharmacokinetics of pomalidomide compared to when pomalidomide was administered alone.. Smoking: In 14 healthy male subjects who smoked 25 cigarettes per day for total of 10 days, after single oral dose of mg POMALYST, Cmax of pomalidomide increased 14% while AUC of pomalidomide decreased 32%, compared to that in 13 healthy male subjects who were non-smokers.. In Vitro StudiesPomalidomide does not inhibit or induce cytochrome p450 enzymes or transporters in vitro.

CLINICAL STUDIES SECTION.

14CLINICAL STUDIES. 14.1 Multiple Myeloma. Trial 1Trial was phase 2, multicenter, randomized open-label study in patients with relapsed multiple myeloma (MM) who were refractory to their last myeloma therapy and had received lenalidomide and bortezomib. Patients were considered relapsed if they had achieved at least stable disease for at least cycle of treatment to at least prior regimen and then developed progressive disease. Patients were considered refractory if they experienced disease progression on or within 60 days of their last therapy. total of 221 patients were randomized to receive POMALYST alone or POMALYST with Low-dose Dex. In Trial 1, the safety and efficacy of POMALYST mg, once daily for 21 of 28 days, until disease progression, were evaluated alone and in combination with Low-dose Dex (40 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged 75 years or younger, or 20 mg/day given only on Days 1, 8, 15, and 22 of each 28-day cycle for patients aged greater than 75 years). Patients in the POMALYST alone arm were allowed to add Low-dose Dex upon disease progression.Table summarizes the baseline patient and disease characteristics in Trial 1. The baseline demographics and disease characteristics were balanced and comparable between the study arms.Table 7:Baseline Demographic and Disease-Related Characteristics Trial 1POMALYST(n=108)POMALYST Low-dose Dex(n=113)Data cutoff: 01 April 2011Patient CharacteristicsMedian age, years (range)61 (37-88)64 (34-88)Age distribution, (%) <65 years65 (60.2)60 (53.1) >=65 years43 (39.8)53 (46.9)Sex, (%) Male57 (52.8)62 (54.9) Female51 (47.2)51 (45.1)Race/ethnicity, (%) White86 (79.6)92 (81.4) Black or African American16 (14.8)17 (15) All other race6 (5.6)4 (3.6)ECOG Performance, (%)Status 0-195 (87.9)100 (88.5)Disease CharacteristicsNumber of prior therapies Median (min, max)5 (2, 12)5 (2, 13)Prior transplant, (%)82 (75.9)84 (74.3)Refractory to bortezomib and lenalidomide, (%)64 (59.3)69 (61.1)Table summarizes the analysis results of overall response rate (ORR) and duration of response (DOR), based on assessments by the Independent Review Adjudication Committee for the treatment arms in Trial 1. ORR did not differ based on type of prior antimyeloma therapy.Table 8: Trial Resultsa Results are prior to the addition of dexamethasone. ORR PR CR per EBMT criteria.CI, confidence interval; NE, not established (the median has not yet been reached).Data cutoff: 01 April 2011POMALYSTa (n=108)POMALYST Low-dose Dex(n=113)ResponseOverall Response Rate (ORR),b (%)8 (7.4)33 (29.2)95% CI for ORR (%)(3.3, 14.1)(21.0, 38.5)Complete Response (CR), (%)0 (0.0)1 (0.9)Partial Response (PR), (%)8 (7.4)32 (28.3)Duration of Response (DOR)Median, monthsNE7.495% CI for DOR (months)NE(5.1, 9.2). Trial 2Trial was Phase multi-center, randomized, open-label study, where POMALYST Low-dose Dex therapy was compared to High-dose Dex in adult patients with relapsed and refractory MM, who had received at least two prior treatment regimens, including lenalidomide and bortezomib, and demonstrated disease progression on or within 60 days of the last therapy. Patients with creatinine clearance >= 45mL/min qualified for the trial. total of 455 patients were enrolled in the trial: 302 in the POMALYST Low-dose Dex arm and 153 in the High-dose Dex arm. Patients in the POMALYST Low-dose Dex arm were administered mg POMALYST orally on Days to 21 of each 28-day cycle. Dexamethasone (40 mg) was administered once per day on Days 1, 8, 15 and 22 of 28-day cycle. Patients 75 years of age started treatment with 20 mg dexamethasone using the same schedule. For the High-dose Dex arm, dexamethasone (40 mg) was administered once per day on Days through 4, through 12, and 17 through 20 of 28-day cycle. Patients 75 years of age started treatment with 20 mg dexamethasone using the same schedule. Treatment continued until patients had disease progression.Baseline patient and disease characteristics were balanced and comparable between the study arms, as summarized in Table 9. Overall, 94% of patients had disease refractory to lenalidomide, 79% had disease refractory to bortezomib and 74% had disease refractory to both lenalidomide and bortezomib.Table 9: Baseline Demographic and Disease-Related Characteristics Trial 2Data cutoff: 01March 2013POMALYST Low-dose DexHigh-dose Dex(N=302)(N=153)Patient CharacteristicsMedian Age, years (range)64 (35, 84)65 (35, 87)Age Distribution (%) 65 years158 (52)74 (48) >= 65 years144 (48)79 (52)Sex (%) Male181 (60)87 (57) Female121 (40)66 (43)Race/Ethnicity (%) White244 (81)113 (74) Black or African American4 (1)3 (2) Asian4 (1)0 (0) Other Race2 (1)2 (1) Not Collected48 (16)35 (23)ECOG Performance (%) Status 0110 (36)36 (24) Status 1138 (46)86 (56) Status 252 (17)25 (16) Status 30 (0)3 (2) Missing2 (1)3 (2)Disease CharacteristicsNumber of Prior Therapies Median, (Min, Max)5 (2, 14)5 (2, 17)Prior stem cell transplant (%)214 (71)105 (69)Refractory to bortezomib and lenalidomide (%)225 (75)113 (74)Table 10 summarizes the progression free survival (PFS) and overall response rate (ORR) based on the assessment by the Independent Review Adjudication Committee (IRAC) review at the final PFS analysis and overall survival (OS) at the OS analysis. PFS was significantly longer with POMALYST Low-dose Dex than High-dose Dex: HR 0.45 (95% CI: 0.35-0.59 < 0.001). OS was also significantly longer with POMALYST Low-dose Dex than High-dose Dex: HR 0.70 (95% CI: 0.54-0.92 = 0.009). The Kaplan-Meier curves for PFS and OS for the ITT population are provided in Figures and 2, respectively.Table 10: Trial ResultsNote: CI=Confidence interval; HD-Dex=High dose dexamethasone; IRAC=Independent Review Adjudication Committee; LD-Dex=Low dose dexamethasone. The median is based on Kaplan-Meier estimate. Based on Cox proportional hazards model comparing the hazard functions associated with treatment groups, stratified by age (<=75 vs >75), diseases population (refractory to both Lenalidomide and Bortezomib vs not refractory to both drugs), and prior number of antimyeloma therapy (=2 vs >2), stratification factors for the trial. The p-value is based on stratified log-rank test with the same stratification factors as the above Cox model.d 53% of patients in the High-dose Dex arm subsequently received POMALYST. Based on Cox proportional hazards model (unstratified) comparing the hazard functions associated with treatment groups. The p-value is based on an unstratified log-rank test. Alpha control for PFS and OS.Data cutoff: 07 Sep 2012 for PFSData cutoff: 01 Mar 2013 for OS and ORRPOMALYST Low-dose DexHigh-dose Dex(N=302)(N=153)Progression Free Survival TimeNumber (%) of events164 (54.3)103 (67.3)Mediana (2-sided 95% CI) (months)3.6 [3.0, 4.6]1.8 [1.6, 2.1]Hazard Ratio (Pom+LD-Dex:HD-Dex) 2-Sided 95% CIb 0.45 [0.35, 0.59]Log-Rank Test 2-sided P-Valuec <0.001Overall Survival TimedNumber (%) of deaths147 (48.7)86 (56.2)Mediana (2-sided 95% CI) (months)12.4 [10.4, 15.3]8.0[6.9, 9.0]Hazard Ratio (Pom+LD-Dex:HD-Dex) 2-Sided 95% CIe 0.70 [0.54, 0.92]Log-Rank Test 2-sided P-Value f, 0.009Overall Response Rate, (%)71 (23.5)6 (3.9) Complete Response1 (0.3)0 Very Good Partial Response8 (2.6)1 (0.7) Partial Response62 (20.5)5 (3.3)Figure 1: Progression Free Survival Based on IRAC Review of Response by IMWG Criteria (Stratified Log Rank Test) (ITT Population)Data cut-off: 07 Sep 2012Figure 2: Kaplan-Meier Curve of Overall Survival (ITT Population)Data cutoff: 01 Mar 2013. Figure 1. Figure 2. 14.2 Kaposi Sarcoma. The clinical trial 12-C-0047 (NCT01495598), was an open label, single center, single arm clinical study that evaluated the safety and efficacy of POMALYST in patients with Kaposi sarcoma (KS). total of 28 patients (18 HIV-positive, 10 HIV-negative) received POMALYST mg orally once daily on Days through 21 of each 28-day cycle until disease progression or unacceptable toxicity. All HIV-positive patients continued highly active antiretroviral therapy (HAART). The trial excluded patients with symptomatic pulmonary or visceral KS, history of venous or arterial thromboembolism, or procoagulant disorders. Patients received thromboprophylaxis with aspirin 81 mg once daily throughout therapy.The median age was 52.5 years, all were male, 75% were White, and 14% Black or African American. Seventy-five percent of patients had advanced disease (T1) at the time of enrollment, 11% had >= 50 lesions, and 75% had received prior chemotherapy.The major efficacy outcome measure was overall response rate (ORR), which included complete response (CR), clinical complete response (cCR), and partial response (PR). Response was assessed by the investigator according to the AIDS Clinical Trial Group (ACTG) Oncology Committee response criteria for KS. The median time to first response was 1.8 months (0.9 to 7.6). Efficacy results are presented in Table 11.Table 11: Trial 12-C-0047 ResultsCI: confidence interval, ORR: overall response rate, CR: complete response, PR: partial response CR includes one HIV-negative patient who achieved cCR. Calculated as date of first documented response to date of first documented disease progression, receipt of new treatment or second course of treatment, or death due to any cause, whichever occurs first. Median estimate is from Kaplan-Meier analysis.From Kaplan-Meier analysis.All PatientsN=28HIV-PositiveN=18HIV-NegativeN=10ORR 1, (%)20 (71)12 (67)8 (80)[95% CI][51, 87](41, 87)(44, 98) CR 1, (%)4 (14)3 (17)1 (10) PR, (%)16 (57)9 (50)7 (70)Duration of Response, KS 2,12.112.510.5Median in months [95% CI]3 [7.6, 16.8][6.5, 24.9][3.9, 24.2]Duration of Response, KS (%)Percent greater than 12 months505838Percent greater than 24 months201725.

CONTRAINDICATIONS SECTION.

4CONTRAINDICATIONS. oPregnancy (4.1)oHypersensitivity (4.2). oPregnancy (4.1). oHypersensitivity (4.2). 4.1Pregnancy. POMALYST is contraindicated in females who are pregnant. POMALYST can cause fetal harm when administered to pregnant female [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Pomalidomide is thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to fetus.. 4.2 Hypersensitivity. POMALYST is contraindicated in patients who have demonstrated severe hypersensitivity (e.g., angioedema, anaphylaxis) to pomalidomide or any of the excipients [see Warnings and Precautions (5.7), Description (11)].

DESCRIPTION SECTION.

11DESCRIPTION. Pomalidomide is thalidomide analog. The chemical name is (RS)-4-Amino-2-(2,6-dioxo-piperidin-3-yl)-isoindoline-1,3-dione and it has the following chemical structure:The empirical formula for pomalidomide is C13H11N3O4 and the gram molecular weight is 273.24.Pomalidomide is yellow solid powder. It has limited to low solubility into organic solvents and it has low solubility in all pH solutions (about 0.01 mg/mL). Pomalidomide has chiral carbon atom which exists as racemic mixture of the R(+) and S(-) enantiomers.POMALYST is available in 1-mg, 2-mg, 3-mg, and 4-mg capsules for oral administration. Each capsule contains pomalidomide as the active ingredient and the following inactive ingredients: mannitol, pregelatinized starch, and sodium stearyl fumarate. The 1-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, white ink, and black ink. The 2-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, FD&C red 3, and white ink. The 3-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, and white ink. The 4-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 1, FD&C blue 2, and white ink.. Chemical Structure.

DOSAGE & ADMINISTRATION SECTION.

2DOSAGE AND ADMINISTRATION. oMM: mg per day taken orally on Days through 21 of repeated 28-day cycles until disease progression (2.2). Refer to section 14.1 for dexamethasone dosing (14.1)oKS: mg per day taken orally on Days through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity (2.3).oModify the dosage for certain patients with renal impairment (2.7, 8.6) or hepatic impairment (2.8, 8.7). oMM: mg per day taken orally on Days through 21 of repeated 28-day cycles until disease progression (2.2). Refer to section 14.1 for dexamethasone dosing (14.1). oKS: mg per day taken orally on Days through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity (2.3).. oModify the dosage for certain patients with renal impairment (2.7, 8.6) or hepatic impairment (2.8, 8.7). 2.1 Pregnancy Testing Prior to Administration. Females of reproductive potential must have negative pregnancy testing and use contraception methods before initiating POMALYST [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].. 2.2 Recommended Dosage for Multiple Myeloma. The recommended dosage of POMALYST is mg once daily orally with or without food on Days through 21 of each 28-day cycle until disease progression. Give POMALYST in combination with dexamethasone [see Clinical Studies (14.1)].. 2.3 Recommended Dosage for Kaposi Sarcoma. The recommended dosage of POMALYST is mg once daily taken orally with or without food on Days through 21 of each 28-day cycle until disease progression or unacceptable toxicity. Continue HAART as HIV treatment in patients with AIDS-related Kaposi sarcoma (KS) [see Clinical Studies (14.2)].. 2.4 Dosage Modifications for Hematologic Adverse Reactions. Multiple Myeloma: Dosage Modifications for Hematologic Adverse ReactionsInitiate new cycle of POMALYST in patients with multiple myeloma (MM) when the neutrophil count is at least 500 per mcL and the platelet count is at least 50,000 per mcL.Dosage modification for POMALYST for hematologic adverse reactions in patients with MM are summarized in Table 1.Table 1:Dosage Modifications for POMALYST for Hematologic in MMAdverse ReactionSeverityDosage Modification Permanently discontinue POMALYST if unable to tolerate mg once daily.ANC= absolute neutrophil countNeutropenia [see Warnings and Precautions (5.5)] oANC less than 500 per mcL or febrile neutropenia (fever greater than or equal to 38.5C and ANC less than 1,000 per mcL)oWithhold POMALYST until ANC is greater than or equal to 500 per mcL; follow CBC weekly.oResume POMALYST dose at mg less than the previous dose.oFor each subsequent drop of ANC less than 500 per mcLoWithhold POMALYST until ANC is greater than or equal to 500 mcL.oResume POMALYST dose at mg less than the previous dose.Thrombocytopenia [see Warnings and Precautions (5.5)]oPlatelets less than 25,000 per mcLoWithhold POMALYST until platelets are greater than or equal to 50,000 per mcL; follow CBC weekly.oResume POMALYST dose at mg less than the previous doseoFor each subsequent drop of platelets less than 25,000 per mcLoWithhold POMALYST until platelets are greater than or equal to 50,000 per mcL.oResume POMALYST at mg less than the previous dose. oANC less than 500 per mcL or febrile neutropenia (fever greater than or equal to 38.5C and ANC less than 1,000 per mcL). oWithhold POMALYST until ANC is greater than or equal to 500 per mcL; follow CBC weekly.. oResume POMALYST dose at mg less than the previous dose.. oFor each subsequent drop of ANC less than 500 per mcL. oWithhold POMALYST until ANC is greater than or equal to 500 mcL.. oResume POMALYST dose at mg less than the previous dose.. oPlatelets less than 25,000 per mcL. oWithhold POMALYST until platelets are greater than or equal to 50,000 per mcL; follow CBC weekly.. oResume POMALYST dose at mg less than the previous dose. oFor each subsequent drop of platelets less than 25,000 per mcL. oWithhold POMALYST until platelets are greater than or equal to 50,000 per mcL.. oResume POMALYST at mg less than the previous dose. Kaposi Sarcoma: Dosage Modifications for Hematologic Adverse ReactionsInitiate new cycle of POMALYST in patients with KS when the neutrophil count is at least 1000 per mcL and the platelet count is at least 75,000 per mcL.Dose modifications for POMALYST for hematologic adverse reactions in patients with KS are summarized in Table 2.Table 2:Dosage Modifications for POMALYST for Hematologic Adverse Reactions in KSAdverse ReactionSeverityDosage Modification Permanently discontinue POMALYST if unable to tolerate 1mg once daily.ANC= absolute neutrophil countNeutropenia [see Warnings and Precautions (5.5)] ANC 500 to less than 1,000 per mcLDay of cycleoWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.oResume POMALYST at the same dose.During cycleoContinue POMALYST at the current dose.ANC less than 500 per mcLoWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.oResume POMALYST at the same dose.Febrile Neutropenia [see Warnings and Precautions (5.5)] ANC less than 1,000 per mcL and single temperature greater than or equal to 38.3C or ANC less than 1,000 per mcL and sustained temperature greater than or equal to 38C for more than houroWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.oResume POMALYST at dose mg less than the previous dose.Thrombocytopenia [see Warnings and Precautions (5.5)] Platelet count 25,000 to less than 50,000 per mcLDay of cycleoWithhold POMALYST until platelet count is greater than or equal to 50,000 per mcL.oResume POMALYST at the same dose.During cycle:oContinue POMALYST at the current dose.Platelet count less than 25,000 per mcLPermanently discontinue POMALYST.. oWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.. oResume POMALYST at the same dose.. oContinue POMALYST at the current dose.. oWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.. oResume POMALYST at the same dose.. oWithhold POMALYST until ANC is greater than or equal to 1,000 per mcL.. oResume POMALYST at dose mg less than the previous dose.. oWithhold POMALYST until platelet count is greater than or equal to 50,000 per mcL.. oResume POMALYST at the same dose.. oContinue POMALYST at the current dose.. 2.5 Dosage Modifications for Non-Hematologic Adverse Reactions. Permanently discontinue POMALYST for angioedema, anaphylaxis, Grade rash, skin exfoliation, bullae, or any other severe dermatologic reaction [See Warnings and Precautions (5.7, 5.12)].For other Grade or toxicities, hold treatment and restart treatment at mg less than the previous dose when toxicity has resolved to less than or equal to Grade at the physicians discretion.. 2.6Dosage Modifications for Strong CYP1A2 Inhibitors. Avoid concomitant use of POMALYST with strong CYP1A2 inhibitors. If concomitant use of strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to mg [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].. 2.7Dosage Modification for Severe Renal Impairment on Hemodialysis. Take POMALYST after completion of dialysis procedure on hemodialysis days [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].oFor patients with MM with severe renal impairment requiring dialysis, reduce the recommended dosage to mg orally daily.oFor patients with KS with severe renal impairment requiring dialysis, reduce the recommended dosage to mg orally daily.. oFor patients with MM with severe renal impairment requiring dialysis, reduce the recommended dosage to mg orally daily.. oFor patients with KS with severe renal impairment requiring dialysis, reduce the recommended dosage to mg orally daily.. 2.8Dosage Modification for Hepatic Impairment. Multiple MyelomaFor patients with MM with mild or moderate hepatic impairment (Child-Pugh or B), reduce the recommended dosage to mg orally daily.For patients with MM with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to mg [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].. Kaposi SarcomaFor patients with KS with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C), reduce the recommended dosage to mg orally daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].. 2.9 Administration. Swallow capsules whole with water. Do not break, chew, or open the capsules.POMALYST may be taken with or without food.

DOSAGE FORMS & STRENGTHS SECTION.

3DOSAGE FORMS AND STRENGTHS. oCapsules:1 mg, dark blue opaque cap and yellow opaque body, imprinted POML on the cap in white ink and 1 mg on the body in black inko2 mg, dark blue opaque cap and orange opaque body, imprinted POML on the cap and 2 mg on the body in white inko3 mg, dark blue opaque cap and green opaque body, imprinted POML on the cap and 3 mg on the body in white inko4 mg, dark blue opaque cap and blue opaque body, imprinted POML on the cap and 4 mg on the body in white ink. oCapsules:1 mg, dark blue opaque cap and yellow opaque body, imprinted POML on the cap in white ink and 1 mg on the body in black ink. o2 mg, dark blue opaque cap and orange opaque body, imprinted POML on the cap and 2 mg on the body in white ink. o3 mg, dark blue opaque cap and green opaque body, imprinted POML on the cap and 3 mg on the body in white ink. o4 mg, dark blue opaque cap and blue opaque body, imprinted POML on the cap and 4 mg on the body in white ink. Capsules: mg, mg, mg, and mg (3).

DRUG INTERACTIONS SECTION.

7DRUG INTERACTIONS. Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to mg (2.6, 7.1, 12.3).. 7.1Drugs That Affect Pomalidomide Plasma Concentrations. CYP1A2 inhibitors:In healthy subjects, co-administration of fluvoxamine, strong CYP1A2 inhibitor, increased Cmax and AUC of pomalidomide by 24% and 125% respectively [see Clinical Pharmacology (12.3)]. Increased pomalidomide exposure may increase the risk of exposure related toxicities. Avoid co-administration of strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine). If co-administration is unavoidable, reduce the POMALYST dose [see Dosage and Administration (2.6)].

FEMALES & MALES OF REPRODUCTIVE POTENTIAL SECTION.

8.3Females and Males of Reproductive Potential. Pregnancy TestingPOMALYST can cause fetal harm when administered during pregnancy [see Use in Specific Populations (8.1)]. Verify the pregnancy status of females of reproductive potential prior to initiating POMALYST therapy and during therapy. Advise females of reproductive potential that they must avoid pregnancy weeks before therapy, while taking POMALYST, during dose interruptions and for at least weeks after completing therapy.Females of reproductive potential must have negative pregnancy tests before initiating POMALYST. The first test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing POMALYST. Once treatment has started and during dose interruptions, pregnancy testing for females of reproductive potential should occur weekly during the first weeks of use, then pregnancy testing should be repeated every weeks in females with regular menstrual cycles. If menstrual cycles are irregular, the pregnancy testing should occur every weeks. Pregnancy testing and counseling should be performed if patient misses her period or if there is any abnormality in her menstrual bleeding. POMALYST treatment must be discontinued during this evaluation.. Contraception. FemalesFemales of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use methods of reliable birth control simultaneously: one highly effective form of contraception tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partners vasectomy, and additional effective contraceptive method male latex or synthetic condom, diaphragm, or cervical cap. Contraception must begin weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for weeks following discontinuation of POMALYST therapy. Reliable contraception is indicated even where there has been history of infertility, unless due to hysterectomy. Females of reproductive potential should be referred to qualified provider of contraceptive methods, if needed.. MalesPomalidomide is present in the semen of males who take POMALYST. Therefore, males must always use latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to weeks after discontinuing POMALYST, even if they have undergone successful vasectomy. Male patients taking POMALYST must not donate sperm.. InfertilityBased on findings in animals, female fertility may be compromised by treatment with POMALYST [see Nonclinical Toxicology (13.1)].

GERIATRIC USE SECTION.

8.5Geriatric Use. Multiple MyelomaOf the total number of patients in clinical studies of POMALYST, 44% were aged older than 65 years, while 10% were aged older than 75 years. No overall differences in effectiveness were observed between these patients and younger patients. In these studies, patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.. Kaposi SarcomaOf the 28 patients who received POMALYST, 11% were 65 years or older, and 3.6% were 75 years of age or older. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.

PREGNANCY SECTION.

8.1Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.. Risk SummaryBased on the mechanism of action [see Clinical Pharmacology (12.1)] and findings from animal studies, POMALYST can cause embryo-fetal harm when administered to pregnant female and is contraindicated during pregnancy [see Contraindications (4), and Warnings and Precautions (5.1)].POMALYST is thalidomide analogue. Thalidomide is human teratogen, inducing high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented, and mortality at or shortly after birth has been reported in about 40% of infants.Pomalidomide was teratogenic in both rats and rabbits when administered during the period of organogenesis. Pomalidomide crossed the placenta after administration to pregnant rabbits (see Data). If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to fetus.If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.. Data. Animal DataPomalidomide was teratogenic in both rats and rabbits in the embryo-fetal developmental studies when administered during the period of organogenesis.In rats, pomalidomide was administered orally to pregnant animals at doses of 25 to 1000 mg/kg/day. Malformations or absence of urinary bladder, absence of thyroid gland, and fusion and misalignment of lumbar and thoracic vertebral elements (vertebral, central, and/or neural arches) were observed at all dose levels. There was no maternal toxicity observed in this study. The lowest dose in rats resulted in an exposure (AUC) approximately 85-fold of the human exposure at the recommended dose of mg/day. Other embryo-fetal toxicities included increased resorptions leading to decreased number of viable fetuses.In rabbits, pomalidomide was administered orally to pregnant animals at doses of 10 to 250 mg/kg/day. Increased cardiac malformations such as interventricular septal defect were seen at all doses with significant increases at 250 mg/kg/day. Additional malformations observed at 250 mg/kg/day included anomalies in limbs (flexed and/or rotated fore- and/or hindlimbs, unattached or absent digit) and associated skeletal malformations (not ossified metacarpal, misaligned phalanx and metacarpal, absent digit, not ossified phalanx, and short not ossified or bent tibia), moderate dilation of the lateral ventricle in the brain, abnormal placement of the right subclavian artery, absent intermediate lobe in the lungs, low-set kidney, altered liver morphology, incompletely or not ossified pelvis, an increased average for supernumerary thoracic ribs, and reduced average for ossified tarsals. No maternal toxicity was observed at the low dose (10 mg/kg/day) that resulted in cardiac anomalies in fetuses; this dose resulted in an exposure (AUC) approximately equal to that reported in humans at the recommended dose of mg/day. Additional embryo-fetal toxicity included increased resorption.Following daily oral administration of pomalidomide from Gestation Day through Gestation Day 20 in pregnant rabbits, fetal plasma pomalidomide concentrations were approximately 50% of the maternal Cmax at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta.

REFERENCES SECTION.

15REFERENCES. 1.OSHA Hazardous Drugs. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html. 1.OSHA Hazardous Drugs. OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.

RENAL IMPAIRMENT SUBSECTION.

8.6Renal Impairment. In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended.For patients with severe renal impairment requiring dialysis, administer POMALYST after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].

SPL MEDGUIDE SECTION.

MEDICATION GUIDEPOMALYST(R) (POM-uh-list)(pomalidomide)capsulesWhat is the most important information should know about POMALYSTBefore you begin taking POMALYST, you must read and agree to all of the instructions in the POMALYST REMS(R) program. Before prescribing POMALYST, your healthcare provider will explain the POMALYST REMS program to you and have you sign the Patient-Physician Agreement Form.POMALYST can cause serious side effects including:oPossible birth defects (deformed babies) or death of an unborn baby. Females who are pregnant or who plan to become pregnant must not take POMALYST. POMALYST is similar to the medicine thalidomide (THALOMID). We know thalidomide can cause severe life-threatening birth defects. POMALYST has not been tested in pregnant females. POMALYST has harmed unborn animals in animal testing. Females must not get pregnant: oFor at least weeks before starting POMALYSToWhile taking POMALYSToDuring any breaks (interruptions) in your treatment with POMALYSToFor at least weeks after stopping POMALYST Females who can become pregnant: oWill have pregnancy tests weekly for weeks, then every weeks if your menstrual cycle is regular, or every weeks if your menstrual cycle is irregular. If you miss your period or have unusual bleeding, you will need to have pregnancy test and receive counseling.oMust agree to use two acceptable forms of birth control at the same time, for at least weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least weeks after stopping POMALYST.oTalk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with POMALYST. If you become pregnant while taking POMALYST, stop taking it right away and call your healthcare provider. If your healthcare provider is not available, you can call Celgene Customer Care Center at 1-888-423-5436.Healthcare providers and patients should report all cases of pregnancy to: oFDA MedWatch at 1-800-FDA-1088, andoCelgene Corporation at 1-888-423-5436There is pregnancy exposure registry that monitors the outcomes of females who take POMALYST during pregnancy, or if their male partner takes POMALYST and they are exposed during pregnancy. You can enroll in this registry by calling Celgene Corporation at the phone number listed above. POMALYST can pass into human semen: oMales, including those who have had vasectomy, must always use latex or synthetic condom during any sexual contact with pregnant female or female that can become pregnant while taking POMALYST, during any breaks (interruptions) in your treatment with POMALYST, and for weeks after stopping POMALYST.oDo not have unprotected sexual contact with female who is or could become pregnant. Tell your healthcare provider if you do have unprotected sexual contact with female who is or could become pregnant.oDo not donate sperm while taking POMALYST, during any breaks (interruptions) in your treatment, and for weeks after stopping POMALYST. If female becomes pregnant with your sperm, the baby may be exposed to POMALYST and may be born with birth defects. Men, if your female partner becomes pregnant, you should call your healthcare provider right away.oBlood clots in your arteries, veins, and lungs, heart attack, and stroke can happen if you take POMALYST. Most people who take POMALYST will also take blood thinner medicine to help prevent blood clots. Before taking POMALYST, tell your healthcare provider:oIf you have had blood clot in the pastoIf you have high blood pressure, smoke, or if you have been told you have high level of fat in your blood (hyperlipidemia)oAbout all the medicines you take. Certain other medicines can also increase your risk for blood clotsCall your healthcare provider or get medical help right away if you get any of the following during treatment with POMALYST:oSigns or symptoms of blood clot in the lung, arm, or leg may include: shortness of breath, chest pain, or arm or leg swellingoSigns or symptoms of heart attack may include: chest pain that may spread to the arms, neck, jaw, back, or stomach area (abdomen), feeling sweaty, shortness of breath, feeling sick or vomitingoSigns or symptoms of stroke may include: sudden numbness or weakness, especially on one side of the body, severe headache or confusion, or problems with vision, speech, or balance. What is POMALYSTPOMALYST is prescription medicine used to treat adults with:oMultiple myeloma. POMALYST is taken along with the medicine dexamethasone, in people who:ohave received at least prior medicines to treat multiple myeloma, including type of medicine known as proteasome inhibitor and lenalidomide, andotheir disease has become worse during treatment or within 60 days of finishing the last treatment oAIDS-related Kaposi sarcoma (KS). POMALYST is taken when highly active antiretroviral therapy (HAART) has not worked well enough or stopped working (failed)oKS who do not have HIV infection (HIV negative).It is not known if POMALYST is safe and effective in children.Who should not take POMALYSTDo not take POMALYST if you:oare pregnant, plan to become pregnant, or become pregnant during treatment with POMALYST. See What is the most important information should know about POMALYSToare allergic to pomalidomide or any of the ingredients in POMALYST. See the end of this Medication Guide for complete list of ingredients in POMALYST.What should tell my healthcare provider before taking POMALYSTBefore you take POMALYST, tell your healthcare provider if you:osmoke cigarettes. POMALYST may not work as well in people who smokeohave liver problemsohave kidney problems and are receiving hemodialysis treatmentohave any other medical conditionsoare breastfeeding. You should not breastfeed during treatment with POMALYST. It is not known if POMALYST passes into your breast milk and can harm your baby.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. POMALYST and other medicines may affect each other, causing serious side effects. Talk with your healthcare provider before taking any new medicines.Know the medicines you take. Keep list of them to show your healthcare provider and pharmacist.How should take POMALYSToTake POMALYST exactly as prescribed and follow all the instructions of the POMALYST REMS program.oSwallow POMALYST capsules whole with water time day. Do not break, chew, or open your capsules.oPOMALYST may be taken with or without food.oTake POMALYST at about the same time each day.oIf you are on hemodialysis, take POMALYST after hemodialysis, on hemodialysis days.oDo not open the POMALYST capsules or handle them any more than needed. If you touch broken POMALYST capsule or the medicine in the capsule, wash the area of your body right away with soap and water.oIf you miss dose of POMALYST and it has been less than 12 hours since your regular time, take it as soon as you remember. If it has been more than 12 hours, just skip your missed dose. Do not take doses at the same time.oIf you take too much POMALYST, call your healthcare provider right away.What should avoid while taking POMALYSToSee What is the most important information should know about POMALYSToFemales: Do not get pregnant and do not breastfeed while taking POMALYST.oMales: Do not donate sperm.oDo not share POMALYST with other people. It may cause birth defects and other serious problems.oDo not donate blood while you take POMALYST, during any breaks (interruptions) in your treatment, and for weeks after stopping POMALYST. If someone who is pregnant gets your donated blood, her baby may be exposed to POMALYST and may be born with birth defects.oPOMALYST can cause dizziness and confusion. Avoid taking other medicines that may cause dizziness and confusion during treatment with POMALYST. Avoid situations that require you to be alert until you know how POMALYST affects you.What are the possible side effects of POMALYSTPOMALYST can cause serious side effects, including:oSee What is the most important information should know about POMALYSToLow white blood cells (neutropenia), low platelets (thrombocytopenia), and low red blood cells (anemia) are common with POMALYST, but can also be serious. You may need blood transfusion or certain medicines if your blood counts drop too low. Your blood counts should be checked weekly for the first weeks of treatment and monthly after that.oSevere liver problems, including liver failure and death. Your healthcare provider should do blood tests to check your liver function during your treatment with POMALYST. Tell your healthcare provider right away if you develop any of the following symptoms of liver problems:oYellowing of your skin or the white part of your eyes (jaundice)oDark or brown (tea-colored) urineoPain on the upper right side of your stomach area (abdomen)oBleeding or bruising more easily than normaloFeeling very tiredoSevere allergic reactions and severe skin reactions can happen with POMALYST and may cause death. Call your healthcare provider if you develop any of the following signs or symptoms during treatment with POMALYST: oa red, itchy, skin rashopeeling of your skin or blistersosevere itchingofeverGet emergency medical help right away if you develop any of the following signs or symptoms during treatment with POMALYST:oswelling of your lips, mouth, tongue, or throatotrouble breathing or swallowingoraised red areas on your skin (hives)oa very fast heartbeatoyou feel dizzy or faintoDizziness and confusion. See What should avoid while taking POMALYSToNerve damage. Stop taking POMALYST and call your healthcare provider if you develop symptoms of nerve damage including: numbness, tingling, pain, burning sensation in your hands, legs, or feet.oRisk of new cancers (malignancies). New cancers, including certain blood cancers (acute myelogenous leukemia or AML) have been seen in people who received POMALYST. Talk with your healthcare provider about your risk of developing new cancers if you take POMALYST.oTumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.Your healthcare provider may tell you to stop taking POMALYST if you develop certain serious side effects during treatment.The most common side effects of POMALYST in people with Multiple Myeloma include:otiredness and weaknessoconstipationonauseaodiarrheaoshortness of breathoupper respiratory tract infectionoback painofeverThe most common side effects of POMALYST in people with KS include:otirednessodiarrheaoabnormal kidney function testsodecreased phosphate and calcium in the bloodorash. See Severe allergic reactions and severe skin reactions above.onauseaoconstipationoincreased blood sugarodecreased albumin in the bloodThese are not all the possible side effects of POMALYST.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store POMALYSToStore POMALYST at room temperature between 68F to 77F (20C to 25C).oReturn any unused POMALYST to Celgene or your healthcare provider.Keep POMALYST and all medicines out of the reach of children.General information about the safe and effective use of POMALYST.Medicines are sometimes prescribed for purposes other than those listed in Medication Guide. Do not take POMALYST for conditions for which it was not prescribed. Do not give POMALYST to other people, even if they have the same symptoms you have. It may harm them and may cause birth defects.If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about POMALYST that is written for health professionals.For more information, call 1-888-423-5436 or go to www.CelgeneRiskManagement.com.What are the ingredients in POMALYSTActive ingredient: pomalidomideInactive ingredients: mannitol, pregelatinized starch, and sodium stearyl fumarate.The 1-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, white ink, and black ink.The 2-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, FD&C red 3, and white ink. The 3-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 2, yellow iron oxide, and white ink. The 4-mg capsule shell contains gelatin, titanium dioxide, FD&C blue 1, FD&C blue 2, and white ink.Manufactured for: Celgene Corporation, Summit, NJ 07901 POMALYST(R) and POMALYST REMS(R) are registered trademarks of Celgene Corporation. Pat. http://www.celgene.com/therapies (C) 2005-2020 Celgene Corporation All rights reserved. POMMG.012 11/2020This Medication Guide has been approved by the U.S. Food and Drug Administration.Revised: November 2020 oPossible birth defects (deformed babies) or death of an unborn baby. Females who are pregnant or who plan to become pregnant must not take POMALYST. POMALYST is similar to the medicine thalidomide (THALOMID). We know thalidomide can cause severe life-threatening birth defects. POMALYST has not been tested in pregnant females. POMALYST has harmed unborn animals in animal testing.. Females must not get pregnant:. oFor at least weeks before starting POMALYSToWhile taking POMALYSToDuring any breaks (interruptions) in your treatment with POMALYSToFor at least weeks after stopping POMALYST. oFor at least weeks before starting POMALYST. oWhile taking POMALYST. oDuring any breaks (interruptions) in your treatment with POMALYST. oFor at least weeks after stopping POMALYST. Females who can become pregnant:. oWill have pregnancy tests weekly for weeks, then every weeks if your menstrual cycle is regular, or every weeks if your menstrual cycle is irregular. If you miss your period or have unusual bleeding, you will need to have pregnancy test and receive counseling.oMust agree to use two acceptable forms of birth control at the same time, for at least weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least weeks after stopping POMALYST.oTalk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with POMALYST.. oWill have pregnancy tests weekly for weeks, then every weeks if your menstrual cycle is regular, or every weeks if your menstrual cycle is irregular. If you miss your period or have unusual bleeding, you will need to have pregnancy test and receive counseling.. oMust agree to use two acceptable forms of birth control at the same time, for at least weeks before, while taking, during any breaks (interruptions) in your treatment, and for at least weeks after stopping POMALYST.. oTalk with your healthcare provider to find out about options for acceptable forms of birth control that you may use to prevent pregnancy before, during, and after treatment with POMALYST.. If you become pregnant while taking POMALYST, stop taking it right away and call your healthcare provider. If your healthcare provider is not available, you can call Celgene Customer Care Center at 1-888-423-5436.Healthcare providers and patients should report all cases of pregnancy to:. oFDA MedWatch at 1-800-FDA-1088, andoCelgene Corporation at 1-888-423-5436There is pregnancy exposure registry that monitors the outcomes of females who take POMALYST during pregnancy, or if their male partner takes POMALYST and they are exposed during pregnancy. You can enroll in this registry by calling Celgene Corporation at the phone number listed above. POMALYST can pass into human semen: oFDA MedWatch at 1-800-FDA-1088, and. oCelgene Corporation at 1-888-423-5436There is pregnancy exposure registry that monitors the outcomes of females who take POMALYST during pregnancy, or if their male partner takes POMALYST and they are exposed during pregnancy. You can enroll in this registry by calling Celgene Corporation at the phone number listed above. POMALYST can pass into human semen: oMales, including those who have had vasectomy, must always use latex or synthetic condom during any sexual contact with pregnant female or female that can become pregnant while taking POMALYST, during any breaks (interruptions) in your treatment with POMALYST, and for weeks after stopping POMALYST.oDo not have unprotected sexual contact with female who is or could become pregnant. Tell your healthcare provider if you do have unprotected sexual contact with female who is or could become pregnant.oDo not donate sperm while taking POMALYST, during any breaks (interruptions) in your treatment, and for weeks after stopping POMALYST. If female becomes pregnant with your sperm, the baby may be exposed to POMALYST and may be born with birth defects.. oMales, including those who have had vasectomy, must always use latex or synthetic condom during any sexual contact with pregnant female or female that can become pregnant while taking POMALYST, during any breaks (interruptions) in your treatment with POMALYST, and for weeks after stopping POMALYST.. oDo not have unprotected sexual contact with female who is or could become pregnant. Tell your healthcare provider if you do have unprotected sexual contact with female who is or could become pregnant.. oDo not donate sperm while taking POMALYST, during any breaks (interruptions) in your treatment, and for weeks after stopping POMALYST. If female becomes pregnant with your sperm, the baby may be exposed to POMALYST and may be born with birth defects.. Men, if your female partner becomes pregnant, you should call your healthcare provider right away.. oBlood clots in your arteries, veins, and lungs, heart attack, and stroke can happen if you take POMALYST. Most people who take POMALYST will also take blood thinner medicine to help prevent blood clots. Before taking POMALYST, tell your healthcare provider:oIf you have had blood clot in the pastoIf you have high blood pressure, smoke, or if you have been told you have high level of fat in your blood (hyperlipidemia)oAbout all the medicines you take. Certain other medicines can also increase your risk for blood clotsCall your healthcare provider or get medical help right away if you get any of the following during treatment with POMALYST:oSigns or symptoms of blood clot in the lung, arm, or leg may include: shortness of breath, chest pain, or arm or leg swellingoSigns or symptoms of heart attack may include: chest pain that may spread to the arms, neck, jaw, back, or stomach area (abdomen), feeling sweaty, shortness of breath, feeling sick or vomitingoSigns or symptoms of stroke may include: sudden numbness or weakness, especially on one side of the body, severe headache or confusion, or problems with vision, speech, or balance. oIf you have had blood clot in the past. oIf you have high blood pressure, smoke, or if you have been told you have high level of fat in your blood (hyperlipidemia). oAbout all the medicines you take. Certain other medicines can also increase your risk for blood clotsCall your healthcare provider or get medical help right away if you get any of the following during treatment with POMALYST:oSigns or symptoms of blood clot in the lung, arm, or leg may include: shortness of breath, chest pain, or arm or leg swellingoSigns or symptoms of heart attack may include: chest pain that may spread to the arms, neck, jaw, back, or stomach area (abdomen), feeling sweaty, shortness of breath, feeling sick or vomitingoSigns or symptoms of stroke may include: sudden numbness or weakness, especially on one side of the body, severe headache or confusion, or problems with vision, speech, or balance.. oSigns or symptoms of blood clot in the lung, arm, or leg may include: shortness of breath, chest pain, or arm or leg swelling. oSigns or symptoms of heart attack may include: chest pain that may spread to the arms, neck, jaw, back, or stomach area (abdomen), feeling sweaty, shortness of breath, feeling sick or vomiting. oSigns or symptoms of stroke may include: sudden numbness or weakness, especially on one side of the body, severe headache or confusion, or problems with vision, speech, or balance.. oMultiple myeloma. POMALYST is taken along with the medicine dexamethasone, in people who:ohave received at least prior medicines to treat multiple myeloma, including type of medicine known as proteasome inhibitor and lenalidomide, andotheir disease has become worse during treatment or within 60 days of finishing the last treatment ohave received at least prior medicines to treat multiple myeloma, including type of medicine known as proteasome inhibitor and lenalidomide, and. otheir disease has become worse during treatment or within 60 days of finishing the last treatment. oAIDS-related Kaposi sarcoma (KS). POMALYST is taken when highly active antiretroviral therapy (HAART) has not worked well enough or stopped working (failed). oKS who do not have HIV infection (HIV negative).. oare pregnant, plan to become pregnant, or become pregnant during treatment with POMALYST. See What is the most important information should know about POMALYST. oare allergic to pomalidomide or any of the ingredients in POMALYST. See the end of this Medication Guide for complete list of ingredients in POMALYST.. osmoke cigarettes. POMALYST may not work as well in people who smoke. ohave liver problems. ohave kidney problems and are receiving hemodialysis treatment. ohave any other medical conditions. oare breastfeeding. You should not breastfeed during treatment with POMALYST. It is not known if POMALYST passes into your breast milk and can harm your baby.. oTake POMALYST exactly as prescribed and follow all the instructions of the POMALYST REMS program.. oSwallow POMALYST capsules whole with water time day. Do not break, chew, or open your capsules.. oPOMALYST may be taken with or without food.. oTake POMALYST at about the same time each day.. oIf you are on hemodialysis, take POMALYST after hemodialysis, on hemodialysis days.. oDo not open the POMALYST capsules or handle them any more than needed. If you touch broken POMALYST capsule or the medicine in the capsule, wash the area of your body right away with soap and water.. oIf you miss dose of POMALYST and it has been less than 12 hours since your regular time, take it as soon as you remember. If it has been more than 12 hours, just skip your missed dose. Do not take doses at the same time.. oIf you take too much POMALYST, call your healthcare provider right away.. oSee What is the most important information should know about POMALYST. oFemales: Do not get pregnant and do not breastfeed while taking POMALYST.. oMales: Do not donate sperm.. oDo not share POMALYST with other people. It may cause birth defects and other serious problems.. oDo not donate blood while you take POMALYST, during any breaks (interruptions) in your treatment, and for weeks after stopping POMALYST. If someone who is pregnant gets your donated blood, her baby may be exposed to POMALYST and may be born with birth defects.. oPOMALYST can cause dizziness and confusion. Avoid taking other medicines that may cause dizziness and confusion during treatment with POMALYST. Avoid situations that require you to be alert until you know how POMALYST affects you.. oSee What is the most important information should know about POMALYST. oLow white blood cells (neutropenia), low platelets (thrombocytopenia), and low red blood cells (anemia) are common with POMALYST, but can also be serious. You may need blood transfusion or certain medicines if your blood counts drop too low. Your blood counts should be checked weekly for the first weeks of treatment and monthly after that.. oSevere liver problems, including liver failure and death. Your healthcare provider should do blood tests to check your liver function during your treatment with POMALYST. Tell your healthcare provider right away if you develop any of the following symptoms of liver problems:. oYellowing of your skin or the white part of your eyes (jaundice). oDark or brown (tea-colored) urine. oPain on the upper right side of your stomach area (abdomen). oBleeding or bruising more easily than normal. oFeeling very tired. oSevere allergic reactions and severe skin reactions can happen with POMALYST and may cause death. Call your healthcare provider if you develop any of the following signs or symptoms during treatment with POMALYST: oa red, itchy, skin rash. opeeling of your skin or blisters. osevere itching. ofever. oswelling of your lips, mouth, tongue, or throat. otrouble breathing or swallowing. oraised red areas on your skin (hives). oa very fast heartbeat. oyou feel dizzy or faint. oDizziness and confusion. See What should avoid while taking POMALYST. oNerve damage. Stop taking POMALYST and call your healthcare provider if you develop symptoms of nerve damage including: numbness, tingling, pain, burning sensation in your hands, legs, or feet.. oRisk of new cancers (malignancies). New cancers, including certain blood cancers (acute myelogenous leukemia or AML) have been seen in people who received POMALYST. Talk with your healthcare provider about your risk of developing new cancers if you take POMALYST.. oTumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.. otiredness and weakness. oconstipation. onausea. odiarrhea. oshortness of breath. oupper respiratory tract infection. oback pain. ofever. otiredness. odiarrhea. oabnormal kidney function tests. odecreased phosphate and calcium in the blood. orash. See Severe allergic reactions and severe skin reactions above.. onausea. oconstipation. oincreased blood sugar. odecreased albumin in the blood. oStore POMALYST at room temperature between 68F to 77F (20C to 25C).. oReturn any unused POMALYST to Celgene or your healthcare provider.

SPL UNCLASSIFIED SECTION.

Embryo-Fetal ToxicityoPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain negative pregnancy tests before starting POMALYST treatment.oFemales of reproductive potential must use forms of contraception or continuously abstain from heterosexual sex during and for weeks after stopping POMALYST treatment [see Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)]. POMALYST is only available through restricted distribution program called POMALYST REMS [see Warnings and Precautions (5.2)]. oPOMALYST is contraindicated in pregnancy. POMALYST is thalidomide analogue. Thalidomide is known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain negative pregnancy tests before starting POMALYST treatment.. oFemales of reproductive potential must use forms of contraception or continuously abstain from heterosexual sex during and for weeks after stopping POMALYST treatment [see Contraindications (4), Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].

STORAGE AND HANDLING SECTION.

Store at 20C-25C (68F-77F); excursions permitted to 15C-30C (59F-86F) [see USP Controlled Room Temperature].Care should be exercised in handling of POMALYST. Do not open or crush POMALYST capsules. If powder from POMALYST contacts the skin, wash the skin immediately and thoroughly with soap and water. If POMALYST contacts the mucous membranes, flush thoroughly with water.Follow procedures for proper handling and disposal of hazardous drugs.

USE IN SPECIFIC POPULATIONS SECTION.

8USE IN SPECIFIC POPULATIONS. oLactation: Advise women not to breastfeed (8.2).. oLactation: Advise women not to breastfeed (8.2).. 8.1Pregnancy. Pregnancy Exposure RegistryThere is pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.. Risk SummaryBased on the mechanism of action [see Clinical Pharmacology (12.1)] and findings from animal studies, POMALYST can cause embryo-fetal harm when administered to pregnant female and is contraindicated during pregnancy [see Contraindications (4), and Warnings and Precautions (5.1)].POMALYST is thalidomide analogue. Thalidomide is human teratogen, inducing high frequency of severe and life-threatening birth defects such as amelia (absence of limbs), phocomelia (short limbs), hypoplasticity of the bones, absence of bones, external ear abnormalities (including anotia, micropinna, small or absent external auditory canals), facial palsy, eye abnormalities (anophthalmos, microphthalmos), and congenital heart defects. Alimentary tract, urinary tract, and genital malformations have also been documented, and mortality at or shortly after birth has been reported in about 40% of infants.Pomalidomide was teratogenic in both rats and rabbits when administered during the period of organogenesis. Pomalidomide crossed the placenta after administration to pregnant rabbits (see Data). If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to fetus.If pregnancy does occur during treatment, immediately discontinue the drug. Under these conditions, refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. The estimated background risk in the U.S. general population of major birth defects is 2%-4% and of miscarriage is 15%-20% of clinically recognized pregnancies.. Data. Animal DataPomalidomide was teratogenic in both rats and rabbits in the embryo-fetal developmental studies when administered during the period of organogenesis.In rats, pomalidomide was administered orally to pregnant animals at doses of 25 to 1000 mg/kg/day. Malformations or absence of urinary bladder, absence of thyroid gland, and fusion and misalignment of lumbar and thoracic vertebral elements (vertebral, central, and/or neural arches) were observed at all dose levels. There was no maternal toxicity observed in this study. The lowest dose in rats resulted in an exposure (AUC) approximately 85-fold of the human exposure at the recommended dose of mg/day. Other embryo-fetal toxicities included increased resorptions leading to decreased number of viable fetuses.In rabbits, pomalidomide was administered orally to pregnant animals at doses of 10 to 250 mg/kg/day. Increased cardiac malformations such as interventricular septal defect were seen at all doses with significant increases at 250 mg/kg/day. Additional malformations observed at 250 mg/kg/day included anomalies in limbs (flexed and/or rotated fore- and/or hindlimbs, unattached or absent digit) and associated skeletal malformations (not ossified metacarpal, misaligned phalanx and metacarpal, absent digit, not ossified phalanx, and short not ossified or bent tibia), moderate dilation of the lateral ventricle in the brain, abnormal placement of the right subclavian artery, absent intermediate lobe in the lungs, low-set kidney, altered liver morphology, incompletely or not ossified pelvis, an increased average for supernumerary thoracic ribs, and reduced average for ossified tarsals. No maternal toxicity was observed at the low dose (10 mg/kg/day) that resulted in cardiac anomalies in fetuses; this dose resulted in an exposure (AUC) approximately equal to that reported in humans at the recommended dose of mg/day. Additional embryo-fetal toxicity included increased resorption.Following daily oral administration of pomalidomide from Gestation Day through Gestation Day 20 in pregnant rabbits, fetal plasma pomalidomide concentrations were approximately 50% of the maternal Cmax at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta.. 8.2Lactation. Risk SummaryThere is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed child, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats (see Data). Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed child from POMALYST, advise women not to breastfeed during treatment with POMALYST.. Data. Animal DataFollowing single oral administration of pomalidomide to lactating rats approximately 14 days postpartum, pomalidomide was transferred into milk, with milk to plasma ratios of 0.63 to 1.46.. 8.3Females and Males of Reproductive Potential. Pregnancy TestingPOMALYST can cause fetal harm when administered during pregnancy [see Use in Specific Populations (8.1)]. Verify the pregnancy status of females of reproductive potential prior to initiating POMALYST therapy and during therapy. Advise females of reproductive potential that they must avoid pregnancy weeks before therapy, while taking POMALYST, during dose interruptions and for at least weeks after completing therapy.Females of reproductive potential must have negative pregnancy tests before initiating POMALYST. The first test should be performed within 10-14 days, and the second test within 24 hours prior to prescribing POMALYST. Once treatment has started and during dose interruptions, pregnancy testing for females of reproductive potential should occur weekly during the first weeks of use, then pregnancy testing should be repeated every weeks in females with regular menstrual cycles. If menstrual cycles are irregular, the pregnancy testing should occur every weeks. Pregnancy testing and counseling should be performed if patient misses her period or if there is any abnormality in her menstrual bleeding. POMALYST treatment must be discontinued during this evaluation.. Contraception. FemalesFemales of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use methods of reliable birth control simultaneously: one highly effective form of contraception tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partners vasectomy, and additional effective contraceptive method male latex or synthetic condom, diaphragm, or cervical cap. Contraception must begin weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for weeks following discontinuation of POMALYST therapy. Reliable contraception is indicated even where there has been history of infertility, unless due to hysterectomy. Females of reproductive potential should be referred to qualified provider of contraceptive methods, if needed.. MalesPomalidomide is present in the semen of males who take POMALYST. Therefore, males must always use latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to weeks after discontinuing POMALYST, even if they have undergone successful vasectomy. Male patients taking POMALYST must not donate sperm.. InfertilityBased on findings in animals, female fertility may be compromised by treatment with POMALYST [see Nonclinical Toxicology (13.1)].. 8.4Pediatric Use. The safety and effectiveness of POMALYST have not been established in pediatric patients. The safety and effectiveness were assessed but not established in two open-label studies: dose escalation study in 25 pediatric patients aged to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and parallel-group study conducted in 47 pediatric patients aged to <17 years with recurrent or progressive high-grade glioma, medulloblastoma, ependymoma, or diffuse intrinsic pontine glioma (DIPG) [NCT03257631]. No new safety signals were observed in pediatric patients across these studies.At the same dose by body surface area, pomalidomide exposure in 55 pediatric patients aged to 17 years old was within the range observed in adult patients with MM but higher than the exposure observed in adult patients with KS [see Clinical Pharmacology (12.3)].. 8.5Geriatric Use. Multiple MyelomaOf the total number of patients in clinical studies of POMALYST, 44% were aged older than 65 years, while 10% were aged older than 75 years. No overall differences in effectiveness were observed between these patients and younger patients. In these studies, patients older than 65 years were more likely than patients less than or equal to 65 years of age to experience pneumonia.. Kaposi SarcomaOf the 28 patients who received POMALYST, 11% were 65 years or older, and 3.6% were 75 years of age or older. The clinical study did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.. 8.6Renal Impairment. In patients with severe renal impairment requiring dialysis, the AUC of pomalidomide increased by 38% and the rate of SAE increased by 64% relative to patients with normal renal function; therefore, starting dose adjustment is recommended.For patients with severe renal impairment requiring dialysis, administer POMALYST after the completion of hemodialysis on dialysis days because exposure of pomalidomide could be significantly decreased during dialysis [see Dosage and Administration (2.7) and Clinical Pharmacology (12.3)].. 8.7Hepatic Impairment. Pomalidomide is metabolized primarily by the liver. Following single dose administration, the AUC of pomalidomide increased 51%, 58%, and 72% in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment, respectively compared to subjects with normal liver function. Dose adjustment is recommended in patients with hepatic impairment [see Dosage and Administration (2.8) and Clinical Pharmacology (12.3)].. 8.8Smoking Tobacco. Cigarette smoking reduces pomalidomide AUC due to CYP1A2 induction. Advise patients that smoking may reduce the efficacy of pomalidomide [see Clinical Pharmacology (12.3)].

WARNINGS AND PRECAUTIONS SECTION.

5WARNINGS AND PRECAUTIONS. oIncreased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and thalidomide analogue (5.4).oHematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia (5.5).oHepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly (5.6).oSevere Cutaneous Reactions: Discontinue POMALYST for severe reactions (5.7).oTumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions (5.11).oHypersensitivity: Monitor patients for potential hypersensitivity. Discontinue POMALYST for angioedema and anaphylaxis (5.12).. oIncreased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and thalidomide analogue (5.4).. oHematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia (5.5).. oHepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly (5.6).. oSevere Cutaneous Reactions: Discontinue POMALYST for severe reactions (5.7).. oTumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions (5.11).. oHypersensitivity: Monitor patients for potential hypersensitivity. Discontinue POMALYST for angioedema and anaphylaxis (5.12).. 5.1Embryo-Fetal Toxicity. POMALYST is thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations (8.1)]. POMALYST is only available through the POMALYST REMS program [see Warnings and Precautions (5.2)]. Females of Reproductive PotentialFemales of reproductive potential must avoid pregnancy for at least weeks before beginning POMALYST therapy, during therapy, during dose interruptions and for at least weeks after completing therapy.Females must commit either to abstain continuously from heterosexual sexual intercourse or to use methods of reliable birth control, beginning weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for weeks following discontinuation of POMALYST 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 POMALYST therapy and then weekly during the first month, then monthly thereafter in females with regular menstrual cycles, or every weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3)]. MalesPomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to weeks after discontinuing POMALYST, even if they have undergone successful vasectomy. Male patients taking POMALYST must not donate sperm [see Use in Specific Populations (8.3)].. Blood DonationPatients must not donate blood during treatment with POMALYST and for weeks following discontinuation of the drug because the blood might be given to pregnant female patient whose fetus must not be exposed to POMALYST.. 5.2POMALYST REMS Program. Because of the embryo-fetal risk [see Warnings and Precautions (5.1)], POMALYST is available only through restricted program under Risk Evaluation and Mitigation Strategy (REMS), the POMALYST REMS program.Required components of the POMALYST REMS program include the following:oPrescribers must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements.oPatients must sign 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)]. oPharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are authorized to receive POMALYST and comply with REMS requirements.Further information about the POMALYST REMS program is available at www.celgeneriskmanagement.com or by telephone at 1-888-423-5436.. oPrescribers must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements.. oPatients must sign 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)]. oPharmacies must be certified with the POMALYST REMS program, must only dispense to patients who are authorized to receive POMALYST and comply with REMS requirements.. 5.3Venous 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 POMALYST. In Trial 2, where anticoagulant therapies were mandated, thromboembolic events occurred in 8.0% of patients treated with POMALYST 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 POMALYST 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 3.0% of patients treated with POMALYST 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 patients underlying risk factors.. 5.4Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to Thalidomide Analogue and Dexamethasone. In two randomized clinical trials in patients with MM, the addition of pembrolizumab to thalidomide analogue plus dexamethasone, use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM with PD-1 or PD-L1 blocking antibody in combination with thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.. 5.5Hematologic Toxicity. Multiple MyelomaIn trials and in patients who received POMALYST Low-dose Dex, neutropenia was the most frequently reported Grade or adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade or 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 weeks and monthly thereafter. Patients may require dose interruption and/or modification [see Dosage and Administration (2.4)].. Kaposi SarcomaIn Trial 12-C-0047, hematologic toxicities were the most common (all grades and Grade or 4) adverse reactions [see Adverse Reactions (6.1)]. Fifty percent of patients had Grade or neutropenia. Monitor patients for hematologic toxicities, especially decreased neutrophils. Monitor complete blood counts every weeks for the first 12 weeks and monthly thereafter. Withhold, reduce the dose, or permanently discontinue POMALYST based on the severity of the reaction [see Dosage and Administration (2.4)].. 5.6Hepatotoxicity. Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes and evaluate. After return to baseline values, treatment at 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 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 POMALYST interruption or discontinuation for Grade or skin rash. Permanently discontinue POMALYST for Grade rash, exfoliative or bullous rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS [see Dosage and Administration (2.5)].. 5.8Dizziness and Confusional State. In trials and in patients who received POMALYST Low-dose Dex, 14% of patients experienced dizziness and 7% of patients experienced confusional state; 1% of patients experienced Grade or dizziness, and 3% of patients experienced Grade or confusional state. Instruct patients to avoid situations where dizziness or confusional state may be problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.. 5.9Neuropathy. In trials and in patients who received POMALYST Low-dose Dex, 18% of patients experienced neuropathy, with approximately 12% of the patients experiencing peripheral neuropathy. Two percent of patients experienced Grade neuropathy in trial 2. There were no cases of Grade 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 POMALYST as an investigational therapy outside of MM.. 5.11 Tumor Lysis Syndrome. Tumor lysis syndrome (TLS) may occur in patients treated with POMALYST. 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 POMALYST have been reported. Permanently discontinue POMALYST for angioedema or anaphylaxis [see Dosage and Administration (2.5)].