Pomalidomida

Uses

Pomalidomida is a thalidomide analogue used in combination with dexamethasone to treat patients with multiple myeloma.

Pomalidomida is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Pomalidomida is also used to associated treatment for these conditions: Refractory Multiple Myeloma

How Pomalidomida works

Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2.

Toxicity

Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia.

Food Interaction

• Take at the same time every day.
• Take with or without food. Administration of pomalidomide with food reduces the AUC and Cmax by 8% and 27%, respectively, and delays Tmax by two and a half hours.

[Moderate] MONITOR: Cigarette smoking may reduce pomalidomide exposure due to induction of CYP450 1A2, the isoenzyme that is responsible for the metabolic clearance of pomalidomide along with CYP450 3A4.

MANAGEMENT: Patients should be advised that smoking may reduce the efficacy of pomalidomide therapy.

Pomalidomida should be taken on an empty stomach, at least 2 hours before or 2 hours after a meal.

Pomalidomida Drug Interaction

Moderate: lactobacillus acidophilus, carfilzomib, bortezomibUnknown: aspirin, charcoal, aspirin, sulfamethoxazole / trimethoprim, daratumumab, dexamethasone, apixaban, furosemide, metoprolol, amlodipine, acetaminophen, clopidogrel, vitamin a topical, lenalidomide, cyanocobalamin, cholecalciferol, ondansetron

Pomalidomida Disease Interaction

Major: thromboembolismModerate: hematologic toxicities, hepatic impairment, neuropathy, renal impairment, smoking, tumor lysis syndrome

Volume of Distribution

Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L

Elimination Route

Pomalidomida is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses.

Half Life

Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours.

Clearance

Total body clearance = 7-10 L/hour

Elimination Route

When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively.

Innovators Monograph

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