POMALIDOMIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POMALIDOMIDE (POMALIDOMIDE).
Immunomodulatory drug with antineoplastic activity; targets cereblon, leading to ubiquitination and degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), resulting in direct cytotoxicity and immune modulation.
| Metabolism | Primarily metabolized by CYP1A2 and CYP3A4; undergoes glucuronidation via UGT1A8. |
| Excretion | Renal (73% as unchanged drug and metabolites), fecal (15%), biliary (minimal). |
| Half-life | Terminal half-life approximately 7.5 hours in patients with normal renal function; prolonged to 9-12 hours in moderate renal impairment. |
| Protein binding | 12-44% bound to albumin and alpha-1-acid glycoprotein; mean ~30%. |
| Volume of Distribution | 62-138 L (approx 0.8-1.7 L/kg); indicates extensive tissue distribution. |
| Bioavailability | Oral: 73% (range 56-85%); high fat meal reduces AUC by 13% but no significant effect. |
| Onset of Action | Oral: 2-4 weeks for hematologic response in multiple myeloma. |
| Duration of Action | Not formally established; continuous therapy until disease progression or unacceptable toxicity; immunomodulatory effects persist days after last dose. |
4 mg orally once daily on days 1-21 of a 28-day cycle, in combination with dexamethasone.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-59 mL/min: 3 mg once daily. CrCl <30 mL/min: 2 mg once daily. Not recommended if CrCl <15 mL/min or requiring dialysis. |
| Liver impairment | Child-Pugh A: 4 mg once daily. Child-Pugh B: 2 mg once daily. Child-Pugh C: 1 mg once daily. |
| Pediatric use | Safety and efficacy not established; no recommended dosing. |
| Geriatric use | No specific dose adjustment; monitor for increased toxicity (e.g., myelosuppression, neurotoxicity) due to age-related organ function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for POMALIDOMIDE (POMALIDOMIDE).
| Breastfeeding | No data on M/P ratio; excreted in animal milk; potential for serious adverse reactions in infant; breastfeeding contraindicated during therapy and for at least 7 days after last dose. |
| Teratogenic Risk | First trimester: High risk of severe birth defects (e.g., limb anomalies, neural tube defects) due to potent teratogenicity; absolutely contraindicated. Second/third trimester: Risk of fetal harm persists; no safe level established; discontinue if possible. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: EMBRYO-FETAL TOXICITY, VENOUS AND ARTERIAL THROMBOEMBOLISM, HEPATOTOXICITY, and INCREASED MORTALITY IN MULTIPLE MYELOMA. Pomalidomide is contraindicated in pregnant women due to teratogenicity. Thromboembolic events (DVT, PE, MI, stroke) are increased. Hepatotoxicity may be severe. In multiple myeloma clinical trials, pomalidomide/dexamethasone was associated with increased mortality in patients with high-risk cytogenetics (del 17p, t(4;14), t(14;16)).
| Common Effects | Fatigue Fever Bone pain Muscle cramp Diarrhea Nausea Constipation Breathing problems Cough Decreased appetite Decreased white blood cell count neutrophils Low blood platelets Decreased white blood cell count lymphocytes Anemia low number of red blood cells |
| Serious Effects |
Pregnancy (absolute); women of childbearing potential not using effective contraception; men not using condoms during sexual activity with pregnant or non-pregnant women; hypersensitivity to pomalidomide or thalidomide analogs; prior severe dermatologic reactions to pomalidomide.
| Precautions |
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| Pregnancy test before start, weekly during first month, then monthly; confirm negative test before each cycle; monitor for fetal growth (ultrasound) if exposure occurs; complete blood counts (CBC) and liver/renal function tests monthly; ECG for QT prolongation if risk factors. |
| Fertility Effects | May impair male fertility via spermatogenesis disruption; reversible upon discontinuation; females: possible anovulation; recommend fertility preservation counseling before treatment. |
| Embryo-fetal toxicity (must use contraception); venous/arterial thromboembolism (consider prophylaxis); hepatotoxicity (monitor LFTs); increased mortality in high-risk multiple myeloma; hematologic toxicity (neutropenia, thrombocytopenia); cardiac toxicity (arrhythmias, heart failure); severe cutaneous reactions; tumor lysis syndrome; renal impairment; fetal risk during pregnancy; avoid use in patients with prior hypersensitivity to thalidomide analogs. |