POMALYST
Clinical safety rating
cautionComprehensive clinical and safety monograph for POMALYST (POMALYST).
Pomalidomide is an immunomodulatory agent with antineoplastic activity. It inhibits proliferation and induces apoptosis of hematopoietic tumor cells. Additionally, it enhances T-cell- and natural killer (NK) cell-mediated immunity and inhibits angiogenesis by blocking the production of pro-angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The exact mechanism of its immunomodulatory and antineoplastic effects is not fully understood.
| Metabolism | Pomalidomide is primarily metabolized by cytochrome P450 (CYP) 1A2 and CYP3A4. It also undergoes hydroxylation and subsequent glucuronidation. Minor pathways include CYP2C19 and CYP2D6. |
| Excretion | Approximately 73% of radiolabeled pomalidomide is excreted in urine (primarily as metabolites, with <2% as unchanged drug) and 15% in feces. Renal clearance is the major elimination pathway. |
| Half-life | Terminal elimination half-life is approximately 7.5 hours in patients with multiple myeloma, allowing for once-daily dosing without accumulation at steady state. |
| Protein binding | 33% bound to human plasma proteins, predominantly to albumin. |
| Volume of Distribution | Apparent volume of distribution is approximately 120 L (1.7 L/kg for a 70 kg individual), indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 73% (range: 66-81%). Administration with a high-fat meal decreases Cmax by 36% and AUC by 26% relative to fasting; therefore, take on an empty stomach. |
| Onset of Action | Oral administration: Clinical effects on tumor response (e.g., reduction in paraprotein) may be observed after 2-4 weeks of continuous dosing; maximal cytopenic effects (neutropenia) typically occur within 21-28 days. |
| Duration of Action | The duration of therapeutic action extends throughout the dosing interval (24 hours) with continuous daily dosing. Hematologic toxicities may persist for 1-2 weeks after drug discontinuation. |
| Molecular Weight | 273.24 Da |
4 mg orally once daily on days 1-21 of repeated 28-day cycles in combination with dexamethasone, for multiple myeloma; for Kaposi sarcoma, 5 mg orally once daily on days 1-21 of 28-day cycles.
| Dosage form | CAPSULE |
| Renal impairment | For CrCl ≥60 mL/min: no adjustment; CrCl 30-59 mL/min: reduce dose to 3 mg once daily; CrCl <30 mL/min: not recommended (no dose established). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose to 3 mg once daily; Child-Pugh C: reduce dose to 2 mg once daily. |
| Pediatric use | Safety and efficacy not established in pediatric patients; no standard dosing. |
| Geriatric use | No specific dose adjustment based on age alone; monitor for toxicity and adjust based on renal function as per adult recommendations. |
| 1st trimester | Contraindicated. Risk of severe birth defects due to teratogenicity (thalidomide analog). Use only if pregnancy is excluded and patient uses effective contraception. |
| 2nd trimester | Contraindicated. No human data; animal studies show fetal harm. Avoid due to potential teratogenicity. |
| 3rd trimester | Contraindicated. Potential fetal harm; avoid use during third trimester. |
Clinical note
Comprehensive clinical and safety monograph for POMALYST (POMALYST).
| Placental transfer | Pomalidomide is known to cross the placenta in humans, similar to other immunomodulatory agents. Fetal exposure confirmed in clinical studies involving pregnant women inadvertently exposed. |
| Breastfeeding | Pomalidomide is excreted in animal milk; human data unavailable. Potential for serious adverse reactions in nursing infants, including neutropenia and developmental toxicity. Advise against breastfeeding during treatment and for at least 4 weeks after last dose. |
| Lactation Rating | Avoid |
| Teratogenic Risk | Pomalidomide is an immunomodulatory drug (IMiD) structurally related to thalidomide, a known human teratogen. It is contraindicated in pregnancy due to high risk of severe birth defects or embryo-fetal death. Fetal exposure during any trimester can cause major congenital malformations, including limb defects, craniofacial anomalies, and cardiovascular abnormalities. Use in females of reproductive potential requires negative pregnancy testing before treatment, and use of two effective contraceptive methods during therapy and for 4 weeks after discontinuation. Pregnancy testing frequency: weekly during first month, then every 2-4 weeks if regular cycles, or every 2 weeks if irregular cycles. |
| Fetal Monitoring | For females of reproductive potential: pregnancy test at initiation (negative with sensitivity at least 25 mIU/mL), weekly for first 4 weeks, then every 2-4 weeks (or every 2 weeks if irregular cycles). For males: avoid seminal fluid exposure to pregnant partner; use condoms during treatment and for 2 weeks after discontinuation. Monitor for fetal development via ultrasound. For thromboembolic risk: monitor for signs/symptoms of venous thromboembolism; consider prophylactic anticoagulation based on underlying risk factors. |
| Fertility Effects | Pomalidomide may impair female fertility based on animal studies; no human fertility data. In male animal studies, no effect on fertility but effects on spermatogenesis observed. Clinical significance in humans is unknown. May cause ovarian failure in women of reproductive age. |
■ FDA Black Box Warning
WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM. Pomalidomide is contraindicated in pregnant women because it can cause severe birth defects or death to an unborn baby. Females of reproductive potential must avoid pregnancy during treatment and for at least 4 weeks after the last dose. Pomalidomide is only available through a restricted distribution program called the POMALYST REMS program. Additionally, pomalidomide significantly increases the risk of venous and arterial thromboembolism (including deep vein thrombosis, pulmonary embolism, myocardial infarction, stroke). Thromboprophylaxis is recommended.
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraceptionHypersensitivity to pomalidomide or any excipientCoadministration with strong CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) - if applicableBreastfeeding
| Precautions | Embryo-fetal toxicity: Can cause fetal harm; females of reproductive potential must use effective contraception and avoid pregnancy. Males should avoid donating sperm., Thromboembolism: Increased risk of venous and arterial thromboembolic events; thromboprophylaxis recommended., Hematologic toxicity: Neutropenia and thrombocytopenia are common; monitor blood counts regularly., Hepatotoxicity: Can cause elevated liver enzymes and hepatic failure; monitor liver function tests., Cardiac toxicity: Increased risk of heart failure, myocardial infarction, and atrial fibrillation., Hypersensitivity reactions: Including angioedema, Stevens-Johnson syndrome, and toxic epidermal necrolysis; discontinue if severe reaction occurs., Tumor lysis syndrome: Monitor patients at risk., Interference with oral contraceptives: May reduce efficacy of oral contraceptives; consider additional non-hormonal contraception. |
| Food/Dietary | Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction. No specific dietary restrictions otherwise; take with or without food. Maintain adequate hydration to prevent tumor lysis syndrome. Avoid alcohol due to increased risk of liver toxicity. |
| Clinical Pearls | Pomalidomide is an immunomodulatory drug used in multiple myeloma after prior therapies including lenalidomide and bortezomib. Requires baseline and periodic CBCs, liver and renal function tests. High risk for venous thromboembolism; prophylaxis with aspirin or anticoagulation recommended. Contraindicated in pregnancy due to severe teratogenicity, necessitating REMS program. Dose adjust for renal impairment (CrCl <45 mL/min) and hepatic impairment (Child-Pugh C). Monitor for tumor lysis syndrome, especially in patients with high tumor burden. |
| Patient Advice | Pomalidomide is a chemotherapy drug that helps treat multiple myeloma by targeting cancer cells. · Do not take if pregnant or planning to become pregnant; use effective contraception during treatment and for 4 weeks after stopping. · Do not breastfeed while taking pomalidomide. · Report any signs of bleeding, bruising, fever, shortness of breath, or chest pain immediately. · Take exactly as prescribed; do not break, chew, or crush capsules; swallow whole with water. · May cause dizziness or drowsiness; avoid driving or operating machinery until you know how it affects you. · Avoid live vaccines while on this medication. · Store at room temperature away from moisture and heat. · Keep all appointments for blood tests and other monitoring. · Inform all healthcare providers that you are taking pomalidomide. |
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