Indications
Pomalidomide is used together with dexamethasone in adults with multiple myeloma (MM). It is meant for people who have already had at least two earlier therapies, including lenalidomide and a proteasome inhibitor, and whose disease has progressed on or within 60 days of finishing the last therapy. Pomalidomide is also used to treat Kaposi sarcoma (KS). This covers adults with AIDS-related Kaposi sarcoma after highly active antiretroviral therapy (HAART) has failed, and adults with Kaposi sarcoma who are HIV-negative.
⚠️ Always consult a registered physician before taking any medicine.
Pharmacology
Pomalidomide is an analogue of thalidomide. It has immunomodulatory, antiangiogenic and antineoplastic properties. Its effects in cells work through its target, cereblon, which is part of a cullin ring E3 ubiquitin ligase enzyme complex. In vitro, when the drug is present, substrate proteins (including Aiolos and Ikaros) are marked for ubiquitination and then broken down. This leads to direct cytotoxic and immunomodulatory effects. In in vitro cellular assays, pomalidomide stopped hematopoietic tumor cells from multiplying and induced apoptosis in them. It also stopped the growth of lenalidomide-resistant multiple myeloma (MM) cell lines. With dexamethasone, it worked together to induce tumor cell apoptosis in both lenalidomide-sensitive and lenalidomide-resistant cell lines. Pomalidomide strengthened T cell- and natural killer (NK) cell-mediated immunity, and it reduced the production of pro-inflammatory cytokines (e.g., TNF-α and IL-6) by monocytes. It showed anti-angiogenic activity in a mouse tumor model and in the in vitro umbilical cord model.
Pharmacodynamics
Exposure-response analyses found no relationship between systemic pomalidomide exposure and either efficacy or safety after a pomalidomide dose of 4 mg.
Pharmacokinetics
In patients with MM who took pomalidomide 4 mg daily, alone or with dexamethasone, steady-state exposure was an AUC (CV%) of 860 (37%) ng-h/mL and a Cmax (CV%) of 75 (32%) ng/mL. In patients with Kaposi sarcoma (KS) who took pomalidomide 5 mg daily, steady-state exposure was an AUC of 462.3 ng-h/mL (82%) and a Cmax of 53.1 ng/mL (50%).
Absorption
After single oral doses of pomalidomide, the maximum plasma concentration (Cmax) is reached 2 to 3 hours after the dose in patients with MM or KS.
Distribution
At steady state, pomalidomide has a mean apparent volume of distribution (Vd/F) of between 62 and 138 L in patients with MM or KS. It passes into semen in healthy subjects, reaching approximately 67% of the plasma level at 4 hours after the dose (~Tmax) following 4 days of 2 mg once-daily dosing. Human plasma protein binding of pomalidomide ranges from 12% to 44% and does not depend on concentration. Pomalidomide is a substrate for P-gp.
Metabolism
Pomalidomide is mainly metabolized in the liver by CYP1A2 and CYP3A4. In vitro, CYP2C19 and CYP2D6 were also seen to contribute in a minor way.
Elimination
In patients with MM or KS, pomalidomide has a mean total body clearance (CL/F) of 7 to 10 L/h. Its median plasma half-life is 9.5 hours in healthy subjects and 7.5 hours in patients with MM or KS.
Excretion
Healthy subjects were given a single oral dose of 14C-pomalidomide. Approximately 73% of the radioactive dose was eliminated in urine and 15% in feces. Of the radiolabeled dose, approximately 2% in urine and 8% in feces was eliminated unchanged as pomalidomide.
Pregnancy & Breastfeeding
Pregnancy: Pomalidomide must not be used by women who are pregnant. It can harm an unborn baby when given to a pregnant woman. Pomalidomide is an analogue of thalidomide, and it caused birth defects in both rats and rabbits when given during the period of organogenesis. If a patient becomes pregnant while taking this medicine, she should be told about the possible risk to the baby.
Lactation: There is no information on whether pomalidomide passes into human milk, what effect it has on a breastfed child, or whether it changes milk production. It did pass into the milk of lactating rats (see Data). Many drugs pass into human milk, and Pomalidomide could cause adverse reactions in a breastfed child, so women are advised not to breastfeed during treatment with Pomalidomide.
⚠️ Talk to your doctor before taking any medicine during pregnancy or while breastfeeding.
Dosage Reference
⚠️ Reference ranges from official sources only. Consult your doctor for personalized dosing.