Overview
11 DESCRIPTION Pomalidomide is a thalidomide analog. The chemical name is ( RS )-4-Amino-2-(2,6-dioxo-piperidin-3-yl)-isoindoline-1,3-dione and it has the following chemical structure: The empirical formula for pomalidomide is C 13 H 11 N 3 O 4 and the gram molecular weight is 273.25. Pomalidomide is a light yellow to yellow colored powder.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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.
Indications
- 1 INDICATIONS AND USAGE Pomalidomide capsules are a thalidomide analogue indicated for the treatment of adult patients: in combination with dexamethasone, for patients with multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy ( 1.1 ). with AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIV-negative.
Common Doses
- 4 mg
- 5 mg
- 1 mg
- 2 mg
Dosage
2 DOSAGE AND ADMINISTRATION MM: 4 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression ( 2.2 ). Refer to section 14.1 for dexamethasone dosing ( 14.1 ). KS: 5 mg per day taken orally on Days 1 through 21 of repeated 28-day cycles until disease progression or unacceptable toxicity ( 2.3 ). Modify the dosage for certain patients with renal impairment ( 2.7 , 8.6 ) or hepatic impairment ( 2.8, 8.7 ). 2.
Black Box Warning
BOXED WARNING WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM Embryo-Fetal Toxicity Pomalidomide capsules are contraindicated in pregnancy. Pomalidomide capsules are 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 capsules treatment.
Contraindications
- 4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Hypersensitivity ( 4.2 ) 4.1 Pregnancy Pomalidomide capsules are contraindicated in females who are pregnant. Pomalidomide capsules can cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1 )]. Pomalidomide is a thalidomide analogue and is teratogenic in both rats and rabbits when administered during the period of organogenesis. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus. 4.
Side Effects
- 6 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.
Interactions
- 7 DRUG INTERACTIONS Strong CYP1A2 Inhibitors: Avoid concomitant use of strong CYP1A2 inhibitors. If concomitant use of a strong CYP1A2 inhibitor is unavoidable, reduce pomalidomide capsules dose to 2 mg ( 2.6 , 7.1 , 12.3 ). 7.1 Drugs That Affect Pomalidomide Plasma Concentrations CYP1A2 inhibitors: In healthy subjects, co-administration of fluvoxamine, a strong CYP1A2 inhibitor, increased C max and AUC of pomalidomide by 24% and 125% respectively [see Clinical Pharmacology (12.3 )]. Increased pomalidomide exposure may increase the risk of exposure related toxicities.