Pomalyst
pomalidomide · Capsule · Oral
• POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe life-threatening birth defects ( 4 , 5.1 , 8.1 ).
• For females of reproductive potential: Exclude pregnancy before start of treatment. Prevent pregnancy during treatment by the use of 2 reliable methods of contraception ( 5.1 , 8.3 ). POMALYST is available only through a restricted program called PS-Pomalidomide REMS ( 5.2 ). VENOUS AND ARTERIAL THROMBOEMBOLISM
• Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Antithrombotic…
Uses
1 INDICATIONS AND USAGE POMALYST is a thalidomide analogue indicated for the treatment of adult patients:
• in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy ( 1.1 ).
• with 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 a confirmatory trial(s) ( 1.2 ). 1.1 Multiple 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 a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy. 1.2 Kaposi Sarcoma POMALYST is indicated for the treatment of:
• Adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART).
• Kaposi 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 a confirmatory trial(s).
Dosage and administration
• MM: 4 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression ( 2.2 ). Refer to section 14.1 for dexamethasone dosing ( 14.1 ).
• KS: 5 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity ( 2.3 ).
• Modify 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 4 mg once daily orally with or without food on Days 1 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 5 mg once daily taken orally with or without food on Days 1 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 Reactions Initiate a 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 MM Adverse Reaction Severity Dosage Modification * Permanently discontinue POMALYST if unable to tolerate 1 mg once daily. ANC= absolute neutrophil count Neutropenia [see Warnings and Precautions (5.5) ]
• ANC less than 500 per mcL or febrile neutropenia (fever greater than or equal to 38.5°C and ANC less than 1,000 per mcL)
• Withhold POMALYST until ANC is greater than or equal to 500 per mcL; follow CBC weekly.
• Resume POMALYST dose at 1 mg less than the previous dose.*
• For each subsequent drop of ANC less than 500 per mcL
• Withhold POMALYST until ANC is greater than or equal to 500 mcL.
• Resume POMALYST dose at 1 mg less than the previous dose.* Thrombocytopenia [see Warnings and Precautions (5.5) ]
• Platelets less than 25,000 per mcL
• Withhold POMALYST until platelets are greater than or equal to 50,000 per mcL; follow CBC weekly.
• Resume POMALYST dose at 1 mg less than the previous dose*
• For each subsequent drop of platelets less than 25,000 per mcL
• Withhold POMALYST until platelets are greater than or equal to 50,000 per mcL.
• Resume POMALYST at 1 mg less than the previous dose* Kaposi Sarcoma: Dosage Modifications for Hematologic Adverse Reactions Initiate a 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 KS Adverse Reaction Severity Dosage Modification * Permanently discontinue POMALYST if unable to tolerate 1mg once daily. ANC= absolute neutrophil count Neutropenia [see Warnings and Precautions (5.5) ] ANC 500 to less than 1,000 per mcL Day 1 of cycle
• Withhold POMALYST until ANC is greater than or equal to 1,000 per mcL.
• Resume POMALYST at the same dose. During cycle
• Continue POMALYST at the current dose. ANC less than 500 per mcL
• Withhold POMALYST until ANC is greater than or equal to 1,000 per mcL.
• Resume 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 38.3°C or ANC less than 1,000 per mcL and sustained temperature greater than or equal to 38°C for more than 1 hour
• Withhold POMALYST until ANC is greater than or equal to 1,000 per mcL.
• Resume POMALYST at dose 1 mg less than the previous dose.* Thrombocytopenia [see Warnings and Precautions (5.5) ] Platelet count 25,000 to less than 50,000 per mcL Day 1 of cycle
• Withhold POMALYST until platelet count is greater than or equal to 50,000 per mcL.
• Resume POMALYST at the same dose. During cycle:
• Continue POMALYST at the current dose. Platelet count less than 25,000 per mcL Permanently discontinue POMALYST. 2.5 Dosage Modifications for Non-Hematologic Adverse Reactions Permanently discontinue POMALYST for angioedema, anaphylaxis, Grade 4 rash, skin exfoliation, bullae, or any other severe dermatologic reaction [See Warnings and Precautions (5.7 , 5.12) ] . For other Grade 3 or 4 toxicities, hold treatment and restart treatment at 1 mg less than the previous dose when toxicity has resolved to less than or equal to Grade 2 at the physician's discretion. 2.6 Dosage Modifications for Strong CYP1A2 Inhibitors Avoid concomitant use of POMALYST with strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . 2.7 Dosage 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) ] .
• For patients with MM with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily.
• For patients with KS with severe renal impairment requiring dialysis, reduce the recommended dosage to 4 mg orally daily.
Dosage forms and strengths
• Capsules: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
• 2 mg, dark blue opaque cap and orange opaque body, imprinted "POML" on the cap and "2 mg" on the body in white ink
• 3 mg, dark blue opaque cap and green opaque body, imprinted "POML" on the cap and "3 mg" on the body in white ink
• 4 mg, dark blue opaque cap and blue opaque body, imprinted "POML" on the cap and "4 mg" on the body in white ink Capsules: 1 mg, 2 mg, 3 mg, and 4 mg ( 3 )
Contraindications
• Pregnancy ( 4.1 )
• Hypersensitivity ( 4.2 ) 4.1 Pregnancy POMALYST is contraindicated in females who are pregnant. POMALYST can cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. Pomalidomide is a 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 a 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) ] .
Warnings and precautions
• Increased Mortality: Observed in patients with MM when pembrolizumab was added to dexamethasone and a thalidomide analogue ( 5.4 ).
• Hematologic Toxicity: Neutropenia was the most frequently reported Grade 3/4 adverse event. Monitor patients for hematologic toxicities, especially neutropenia ( 5.5 ).
• Hepatotoxicity: Hepatic failure including fatalities; monitor liver function tests monthly ( 5.6 ).
• Severe Cutaneous Reactions: Discontinue POMALYST for severe reactions ( 5.7 ).
• Tumor Lysis Syndrome (TLS): Monitor patients at risk of TLS (i.e., those with high tumor burden) and take appropriate precautions ( 5.11 ).
• Hypersensitivity: Monitor patients for potential hypersensitivity. Discontinue POMALYST for angioedema and anaphylaxis ( 5.12 ). 5.1 Embryo-Fetal Toxicity POMALYST is a thalidomide analogue and is contraindicated for use during pregnancy. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death [see Use in Specific Populations (8.1) ] . POMALYST is only available through PS-Pomalidomide REMS [see Warnings and Precautions (5.2) ]. Females of Reproductive Potential Females of reproductive potential must avoid pregnancy for at least 4 weeks before beginning POMALYST therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy. Females must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control, beginning 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for 4 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 2 weeks in females with irregular menstrual cycles [see Use in Specific Populations (8.3) ]. Males Pomalidomide is present in the semen of patients receiving the drug. Therefore, males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Male patients taking POMALYST must not donate sperm [see Use in Specific Populations (8.3) ] . Blood Donation Patients must not donate blood during treatment with POMALYST and for 4 weeks following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST. 5.2 PS-Pomalidomide REMS Because of the embryo-fetal risk [see Warnings and Precautions (5.1) ] , POMALYST is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), "PS-Pomalidomide REMS" . Required components of PS-Pomalidomide REMS include the following:
• Prescribers must be certified with PS-Pomalidomide REMS by enrolling and complying with the REMS requirements.
• Patients must sign a Patient-Physician Agreement Form and comply with the REMS requirements. In particular, female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ] and males must comply with contraception requirements [see Use in Specific Populations (8.3) ] .
• Pharmacies must be certified with PS-Pomalidomide REMS , must only dispense to patients who are authorized to receive POMALYST and comply with REMS requirements. Further information about PS-Pomalidomide REMS is available at www.PS-PomalidomideREMS.com or by telephone at 1-888-423-5436. 5.3 Venous and Arterial Thromboembolism Venous thromboembolic events (deep venous thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke) have been observed in patients treated with 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 patient's underlying risk factors. 5.4 Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone In two randomized clinical trials in patients with MM, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone, a use for which no PD-1 or PD-L1 blocking antibody is indicated, resulted in increased mortality. Treatment of patients with MM with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials. 5.5 Hematologic Toxicity Multiple Myeloma In trials 1 and 2 in patients who received POMALYST + Low-dose Dex, neutropenia was the most frequently reported Grade 3 or 4 adverse reaction, followed by anemia and thrombocytopenia. Neutropenia of any grade was reported in 51% of patients in both trials. The rate of Grade 3 or 4 neutropenia was 46%.
Side effects
The following clinically significant adverse reactions are described in detail in other labeling sections:
• Embryo-Fetal Toxicity [see Warnings and Precautions (5.1 , 5.2) ]
• Venous and Arterial Thromboembolism [see Warnings and Precautions (5.3) ]
• Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and Precautions (5.4) ]
• Hematologic Toxicity [see Warnings and Precautions (5.5)]
• Hepatotoxicity [see Warnings and Precautions (5.6) ]
• Severe Cutaneous Reactions [see Warnings and Precautions (5.7) ]
• Dizziness and Confusional State [see Warnings and Precautions (5.8) ]
• Neuropathy [see Warnings and Precautions (5.9) ]
• Risk of Second Primary Malignancies [see Warnings and Precautions (5.10) ]
• Tumor Lysis Syndrome [see Warnings and Precautions (5.11) ]
• Hypersensitivity [see Warnings and Precautions (5.12) ]
• MM: Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain, and pyrexia ( 6.1 ).
• KS: 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 Bristol Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Multiple Myeloma (MM) In Trial 1, data were evaluated from 219 patients (safety population) who received treatment with POMALYST + Low-dose Dex (112 patients) or POMALYST alone (107 patients). Median number of treatment cycles was 5. Sixty-seven percent of patients in the study had a dose interruption of either drug due to adverse reactions. Forty-two percent of patients in the study had a dose reduction of either drug due to adverse reactions. The discontinuation rate due to adverse reactions was 11%. In Trial 2, data were evaluated from 450 patients (safety population) who received treatment with POMALYST + Low-dose Dex (300 patients) or High-dose Dexamethasone (High-dose Dex) (150 patients). The median number of treatment cycles for the POMALYST + Low-dose Dex arm was 5. In the POMALYST + Low-dose Dex arm, 67% of patients had a dose interruption of POMALYST, the median time to the first dose interruption of POMALYST was 4.1 weeks. Twenty-seven percent of patients had a dose reduction of POMALYST, the median time to the first dose reduction of POMALYST was 4.5 weeks. Eight percent of patients discontinued POMALYST due to adverse reactions. Tables 3 and 4 summarize the adverse reactions reported in Trials 1 and 2, respectively. Table 3: Adverse Reactions in Any POMALYST Treatment Arm in Trial 1* * Regardless of attribution of relatedness to POMALYST. a POMALYST alone arm includes all patients randomized to the POMALYST alone arm who took study drug; 61 of the 107 patients had dexamethasone added during the treatment period. b Serious adverse reactions were reported in at least 2 patients in any POMALYST treatment arm. Data cutoff: 01 March 2013 All Adverse Reactions ≥10% in Either Arm Grade 3 or 4 ≥5% in Either Arm Body System Adverse Reaction POMALYST a (N=107) POMALYST + Low-dose Dex (N=112) POMALYST (N=107) POMALYST + Low-dose Dex (N=112) Number (%) of patients with at least one adverse reaction 107 (100) 112 (100) 98 (92) 102 (91) Blood and lymphatic system disorders Neutropenia b 57 (53) 55 (49) 51 (48) 46 (41) Anemia b 41 (38) 47 (42) 25 (23) 24 (21) Thrombocytopenia b 28 (26) 26 (23) 24 (22) 21 (19) Leukopenia 14 (13) 22 (20) 7 (7) 11 (10) Febrile neutropenia b <10% <10% 6 (6) 3 (3) Lymphopenia 4 (4) 17 (15) 2 (2) 8 (7) General disorders and administration site conditions Fatigue and asthenia b 62 (58) 70 (63) 13 (12) 19 (17) Edema peripheral 27 (25) 19 (17) 0 (0.0) 0 (0.0) Pyrexia b 25 (23) 36 (32) <5% <5% Chills 11 (10) 14 (13) 0 (0.0) 0 (0.0) Gastrointestinal disorders Nausea b 39 (36) 27 (24) <5% <5% Constipation b 38 (36) 41 (37) <5% <5% Diarrhea 37 (35) 40 (36) <5% <5% Vomiting b 15 (14) 16 (14) <5% 0 (0.0) Musculoskeletal and connective tissue disorders Back pain b 37 (35) 36 (32) 15 (14) 11 (10) Musculoskeletal chest pain 25 (23) 22 (20) <5% 0 (0.0) Muscle spasms 23 (21) 22 (20) <5% <5% Arthralgia 18 (17) 17 (15) <5% <5% Muscular weakness 15 (14) 15 (13) 6 (6) 4 (4) Bone pain 13 (12) 8 (7) <5% <5% Musculoskeletal pain 13 (12) 19 (17) <5% <5% Pain in extremity 8 (7) 16 (14) 0 (0.0) <5% Infections and infestations Upper respiratory tract infection 40 (37) 32 (29) <5% <5% Pneumonia b 30 (28) 38 (34) 21 (20) 32 (29) Urinary tract infection b 11 (10) 19 (17) 2 (2) 10 (9) Sepsis b <10% <10% 6 (6) 5 (4) Metabolism and nutrition disorders Decreased appetite 25 (23) 21 (19) <5% 0 (0.0) Hypercalcemia b 23 (21) 13 (12) 11 (10) 1 (<1) Hypokalemia 13 (12) 13 (12) <5% <5% Hyperglycemia 12 (11) 17 (15) <5% <5% Hyponatremia 12 (11) 14 (13) <5% <5% Dehydration b <10% <10% 5 (4.7) 6 (5.4) Hypocalcemia 6 (6) 13 (12) 0 (0.0) <5% Respiratory, thoracic and mediastinal disorders Dyspnea b 38 (36) 50 (45) 8 (7) 14 (13) Cough 18 (17) 25 (22) 0 (0.0) 0 (0.0) Epistaxis 18 (17) 12 (11) <5% 0 (0.0) Productive cough 10 (9) 14 (13) 0 (0.0) 0 (0.0) Oropharyngeal pain 6 (6) 12 (11) 0 (0.0) 0 (0.0) Nervous system disorders Dizziness 24 (22) 20 (18) <5% <5% Peripheral neuropathy 23 (21) 20 (18) 0 (0.0) 0 (0.0) Headache 16 (15) 15 (13) 0 (0.0) <5% Tremor 11 (10) 15 (13) 0 (0.0) 0 (0.0) Skin and subcutaneous tissue disorders Rash 22 (21) 18 (16) 0 (0.0) <5% Pruritus 16 (15) 10 (9…
Drug interactions
Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce POMALYST dose to 2 mg ( 2.6 , 7.1 , 12.3 ). 7.1 Drugs That Affect Pomalidomide Plasma Concentrations CYP1A2 inhibitors : In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased C max 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) ] .
Use in specific populations
• Lactation: Advise women not to breastfeed ( 8.2 ). 8.1 Pregnancy Pregnancy Exposure Registry There is a 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 the REMS Call Center at 1-888-423-5436. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1) ] and findings from animal studies, POMALYST can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4) , and Warnings and Precautions (5.1) ] . POMALYST is a thalidomide analogue. Thalidomide is a human teratogen, inducing a 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 a 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 the REMS Call Center 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 Data Pomalidomide 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 4 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 a 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 4 mg/day. Additional embryo-fetal toxicity included increased resorption. Following daily oral administration of pomalidomide from Gestation Day 7 through Gestation Day 20 in pregnant rabbits, fetal plasma pomalidomide concentrations were approximately 50% of the maternal C max at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta. 8.2 Lactation Risk Summary There 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 a breastfed child from POMALYST, advise women not to breastfeed during treatment with POMALYST. Data Animal Data Following a 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. 8.3 Females and Males of Reproductive Potential Pregnancy Testing POMALYST 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 4 weeks before therapy, while taking POMALYST, during dose interruptions and for at least 4 weeks after completing therapy. Females of reproductive potential must have 2 negative pregnancy tests before initiating POMALYST.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a 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 the REMS Call Center at 1-888-423-5436. Risk Summary Based on the mechanism of action [see Clinical Pharmacology (12.1) ] and findings from animal studies, POMALYST can cause embryo-fetal harm when administered to a pregnant female and is contraindicated during pregnancy [see Contraindications (4) , and Warnings and Precautions (5.1) ] . POMALYST is a thalidomide analogue. Thalidomide is a human teratogen, inducing a 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 a 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 the REMS Call Center 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 Data Pomalidomide 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 4 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 a 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 4 mg/day. Additional embryo-fetal toxicity included increased resorption. Following daily oral administration of pomalidomide from Gestation Day 7 through Gestation Day 20 in pregnant rabbits, fetal plasma pomalidomide concentrations were approximately 50% of the maternal C max at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta.
Pediatric use
8.4 Pediatric 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: a dose escalation study in 25 pediatric patients aged 5 to <17 with recurrent, progressive or refractory CNS tumors [NCT02415153] and a parallel-group study conducted in 47 pediatric patients aged 4 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 4 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) ] .
Geriatric use
8.5 Geriatric Use Multiple Myeloma Of 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 Sarcoma Of 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.
Overdosage
Hemodialysis can remove pomalidomide from circulation.
Description
Pomalidomide is a 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 C 13 H 11 N 3 O 4 and the gram molecular weight is 273.24. Pomalidomide is a 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 a chiral carbon atom which exists as a 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. pom-chem-structure
Mechanism of action
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, a component of a 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 T cell- and natural killer (NK) cell-mediated immunity and inhibited production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. Pomalidomide demonstrated anti-angiogenic activity in a mouse tumor model and in the in vitro umbilical cord model.
How supplied
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 1 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 ink 2 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 ink 3 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 ink 4 mg bottles of 21 (NDC 59572-504-21) 4 mg bottles of 100 (NDC 59572-504-00) Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [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. 1
Storage
Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [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. 1
Patient information
Advise the patient to read the FDA-approved patient labeling (Medication Guide). Embryo-Fetal Toxicity Advise patients that POMALYST is contraindicated in pregnancy [see Contraindications (4) ] . POMALYST is a thalidomide analogue and may cause serious birth defects or death to a developing baby [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] .
• Advise females of reproductive potential that they must avoid pregnancy while taking POMALYST and for at least 4 weeks after completing therapy.
• Initiate POMALYST treatment in females of reproductive potential only following a negative pregnancy test.
• Advise females of reproductive potential of the importance of monthly pregnancy tests and the need to use 2 different forms of contraception, including at least 1 highly effective form, simultaneously during POMALYST therapy, during dose interruptions, and for 4 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 a partner's vasectomy. Additional effective contraceptive methods include latex or synthetic condom, diaphragm, and cervical cap.
• Instruct 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.
• Advise patient that if her healthcare provider is not available, she should call the REMS Call Center at 1-888-423-5436 [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ].
• Advise males to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy.
• Advise male patients taking POMALYST that they must not donate sperm [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3) ] .
• All patients must be instructed to not donate blood while taking POMALYST and for 4 weeks following discontinuation of POMALYST [see Warnings and Precautions (5.1) ] . PS-Pomalidomide REMS Because of the risk of embryo-fetal toxicity, POMALYST is only available through a restricted program called PS-Pomalidomide REMS [see Warnings and Precautions (5.2) ] .
• Patients must sign a 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) ] .
• POMALYST is available only from pharmacies that are certified in PS-Pomalidomide REMS. Provide patients with the telephone number and website for information on how to obtain the product. Pregnancy Exposure Registry Inform females that there is a 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 Thromboembolism Inform 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 Toxicities Inform 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) ] . Hepatotoxicity Inform 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 Reactions Inform 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 State Inform patients of the potential risk of dizziness and confusional state with the drug, to avoid situations where dizziness or confusional state may be a problem, and not to take other medications that may cause dizziness or confusional state without adequate medical advice [see Warnings and Precautions (5.8) ] . Neuropathy Inform 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 Malignancies Inform 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 Syndrome Inform 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) ] . Hypersensitivity Inform 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 Tobacco Advise patients that smoking tobacco may reduce the efficacy of POMALYST [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3) ] .
Label text from the FDA structured product label by Celgene Corporation (revised Feb 26, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pomalidomide in 4 products
Pomalyst NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 59572-501 | Pomalidomide 1 mg/1 Capsule | Celgene Corporation | NDA |
| 59572-502 | Pomalidomide 2 mg/1 Capsule | Celgene Corporation | NDA |
| 59572-503 | Pomalidomide 3 mg/1 Capsule | Celgene Corporation | NDA |
| 59572-504 | Pomalidomide 4 mg/1 Capsule | Celgene Corporation | NDA |
Frequently asked questions
What is Pomalyst used for?
1 INDICATIONS AND USAGE POMALYST is a thalidomide analogue indicated for the treatment of adult patients: • in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy ( 1.1 ). • with…
What are the side effects of Pomalyst?
The following clinically significant adverse reactions are described in detail in other labeling sections: • Embryo-Fetal Toxicity [see Warnings and Precautions (5.1 , 5.2) ] • Venous and Arterial Thromboembolism [see Warnings and Precautions (5.3) ] • Increased Mortality in Patients with Multiple Myeloma When Pembrolizumab Is Added to a Thalidomide Analogue and Dexamethasone [see Warnings and… See the full label for the complete list.
Who makes Pomalyst?
Pomalyst is listed by 1 labeler in the FDA NDC directory, including Celgene Corporation.