Dosage & Administration
Pomalyst Prescribing Information
Embryo-Fetal Toxicity
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- POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.
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- Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 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 a restricted distribution program called PS-Pomalidomide REMS [see Warnings and Precautions (5.2)]. Information about PS-Pomalidomide REMS is available at www.PS-PomalidomideREMS.com or by calling the REMS Call Center at 1-888-423-5436.
Venous and Arterial Thromboembolism
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- Deep 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 patient's underlying risk factors [see Warnings and Precautions (5.3)].
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.
Kaposi Sarcoma
POMALYST is indicated for the treatment of:
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- Adult patients with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART).
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- 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).
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)].
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)].
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)].
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.
| 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)] |
|
|
|
| |
Thrombocytopenia [see Warnings and Precautions (5.5)] |
|
|
|
| |
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.
| 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
During cycle
|
ANC less than 500 per mcL |
| |
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 |
|
Thrombocytopenia [see Warnings and Precautions (5.5)] | Platelet count 25,000 to less than 50,000 per mcL | Day 1 of cycle
During cycle:
|
Platelet count less than 25,000 per mcL | Permanently discontinue POMALYST. | |
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.
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)].
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)].
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- For patients with MM with severe renal impairment requiring dialysis, reduce the recommended dosage to 3 mg orally daily.
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- For patients with KS with severe renal impairment requiring dialysis, reduce the recommended dosage to 4 mg orally daily.
Dosage Modification for Hepatic Impairment
Multiple Myeloma
For patients with MM with mild or moderate hepatic impairment (Child-Pugh A or B), reduce the recommended dosage to 3 mg orally daily.
For patients with MM with severe hepatic impairment (Child-Pugh C), reduce the recommended dosage to 2 mg [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Kaposi Sarcoma
For patients with KS with mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C), reduce the recommended dosage to 3 mg orally daily [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
Administration
Swallow capsules whole with water. Do not break, chew, or open the capsules.
POMALYST may be taken with or without food.
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- 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
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- 2 mg, dark blue opaque cap and orange opaque body, imprinted "POML" on the cap and "2 mg" on the body in white ink
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- 3 mg, dark blue opaque cap and green opaque body, imprinted "POML" on the cap and "3 mg" on the body in white ink
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- 4 mg, dark blue opaque cap and blue opaque body, imprinted "POML" on the cap and "4 mg" on the body in white ink
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 Cmax at all dosages (5 to 250 mg/kg/day), indicating that pomalidomide crossed the placenta.
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.
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. 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 4 weeks of use, then pregnancy testing should be repeated every 4 weeks in females with regular menstrual cycles. If menstrual cycles are irregular, the pregnancy testing should occur every 2 weeks. Pregnancy testing and counseling should be performed if a patient misses her period or if there is any abnormality in her menstrual bleeding. POMALYST treatment must be discontinued during this evaluation.
Contraception
Females
Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use 2 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 partner's vasectomy, and 1 additional effective contraceptive method – male latex or synthetic condom, diaphragm, or cervical cap. Contraception must begin 4 weeks prior to initiating treatment with POMALYST, during therapy, during dose interruptions, and continuing for 4 weeks following discontinuation of POMALYST therapy. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy. Females of reproductive potential should be referred to a qualified provider of contraceptive methods, if needed.
Males
Pomalidomide is present in the semen of males who take POMALYST. 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.
Infertility
Based on findings in animals, female fertility may be compromised by treatment with POMALYST [see Nonclinical Toxicology (13.1)].
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
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.
Renal 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)].
Hepatic 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)].
Smoking 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)].
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.
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)].