Pomalidomide (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- POMALIDOMIDE
- POMALYST
Boxed Warning
Embryo-Fetal Toxicity Pomalidomide is contraindicated in pregnancy. Pomalidomide 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 pomalidomide treatment. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping pomalidomide treatment [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 , 8.3 )]. Pomalidomide is only available through a restricted distribution program called PS-Pomalidomide REMS [see Warnings and Precautions ( 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 pomalidomide. 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 )].
Adverse Reactions
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)]
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.
Overdosage
Hemodialysis can remove pomalidomide from circulation.