Lenalidomide

Brand Names: Lenalidomide

Drug Class: Thalidomide Analog

Overview

11 DESCRIPTION Lenalidomide, a thalidomide analogue, is an immunomodulatory agent with antiangiogenic and antineoplastic properties. The chemical name is 3-(4-amino-1-oxo 1,3-dihydro-2 H -isoindol-2-yl) piperidine-2,6-dione and it has the following chemical structure: 3-(4-amino-1-oxo 1,3-dihydro-2 H -isoindol-2-yl) piperidine-2,6-dione The empirical formula for lenalidomide is C 13 H 13 N 3 O 3...

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Lenalidomide is an analogue of thalidomide with immunomodulatory, antiangiogenic, and antineoplastic properties. Cellular activities of lenalidomide 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, Ikaros, and CK1α) are targeted for ubiquitination and subsequent degradation leading to direct cytotoxic and immunomodulatory effects. Lenalidomide inhibits proliferation and induces apoptosis of certain hematopoietic tumor cells including MM, mantle cell lymphoma, and del (5q) myelodysplastic syndromes in vitro .

Indications

  • 1 INDICATIONS AND USAGE Lenalidomide is a thalidomide analogue indicated for the treatment of adult patients with: Multiple myeloma (MM), in combination with dexamethasone ( 1.1 ). Transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities ( 1.2 ). Mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib ( 1.3 ).

Common Doses

  • 25 mg
  • 10 mg
  • 2.5 mg
  • 5 mg

Dosage

2 DOSAGE AND ADMINISTRATION MM combination therapy: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles. ( 2.1 ). MDS: 10 mg once daily ( 2.2 ). MCL: 25 mg once daily orally on Days 1 to 21 of repeated 28-day cycles ( 2.3 ). Renal impairment: Adjust starting dose based on the creatinine clearance value ( 2.6 ). For concomitant therapy doses, see Full Prescribing Information ( 2.1 , 14.1 ). 2.1 Recommended Dosage for Multiple Myeloma Lenalidomide Capsules Combination Therapy The recommended starting dose of lenalidomide capsules is 25 mg orally once daily on Days 1 to 21 of...

Black Box Warning

WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS and ARTERIAL THROMBOEMBOLISM Embryo-Fetal Toxicity Do not use lenalidomide capsules during pregnancy. Lenalidomide, a thalidomide analogue, caused limb abnormalities in a developmental monkey study. Thalidomide is a known human teratogen that causes severe life-threatening human birth defects. If lenalidomide is used during pregnancy, it may cause birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting lenalidomide treatment.

Contraindications

  • 4 CONTRAINDICATIONS Pregnancy ( Boxed Warning , 4.1 , 5.1 , 8.1 ). Demonstrated severe hypersensitivity to lenalidomide ( 4.2 , 5.9 , 5.15 ). 4.1 Pregnancy Lenalidomide capsules can cause fetal harm when administered to a pregnant female. Limb abnormalities were seen in the offspring of monkeys that were dosed with lenalidomide during organogenesis. This effect was seen at all doses tested. Due to the results of this developmental monkey study, and lenalidomide’s structural similarities to thalidomide, a known human teratogen, lenalidomide is contraindicated in females who are pregnant [see...

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in detail in other sections of the prescribing information: Embryo-Fetal Toxicity [see Boxed Warning , Warnings and Precautions ( 5.1 , 5.2 )] Hematologic Toxicity [see Boxed Warning , Warnings and Precautions ( 5.3 )] Venous and Arterial Thromboembolism [see Boxed Warning , Warnings and Precautions ( 5.4 )] Increased Mortality in Patients with CLL [see Warnings and Precautions ( 5.5 )] Second Primary Malignancies [see Warnings and Precautions ( 5.

Interactions

  • 7 DRUG INTERACTIONS Digoxin: Monitor digoxin plasma levels periodically due to increased C max and AUC with concomitant lenalidomide capsules therapy ( 7.1 ). Concomitant use of erythropoietin stimulating agents or estrogen containing therapies with lenalidomide capsules may increase the risk of thrombosis ( 7.2 ). 7.1 Digoxin When digoxin was co-administered with multiple doses of lenalidomide capsules (10 mg/day) the digoxin C max and AUC inf were increased by 14%.