Lenalidomide

Indications

Lenalidomide is used for: Myelodysplastic disease, Multiple myeloma

Adult Dose

Oral Myelodysplastic disease Adult: Initially, 10 mg once daily for 21 consecutive days of repeated 28-day cycle. Multiple myeloma Adult: In combination w/ dexamethasone. Lenalidomide: Initially, 25 mg once daily for 21 consecutive days of repeated 28-day cycle. Dexamethasone: 40 mg once daily on days 1-4, 9-12 and 17-20 of each 28-day cycle, for the 1st 4 cycles, then 40 mg once daily on days 1-4 of each 28-day cycle. Elderly: No dosage adjustment needed.

Child Dose

<18 years old: Safety and efficacy not established

Renal Dose

Myelodysplastic disease: Moderate: 5 mg once daily. Severe (not requiring dialysis): 5 mg every other day. End-stage renal disease: 5 mg 3 times/wk after dialysis. Multiple myeloma: Moderate: 10 mg once daily may be increased to 15 mg once daily after 2 cycles if needed. Severe (not requiring dialysis): 15 mg every other day, may be increased to 10 mg once daily if needed. End-stage renal disease: 5 mg once daily after dialysis.

Administration

May be taken with or without food. Swallow whole, do not break/chew/open.

Contra Indications

Pregnancy and lactation; sexually active women of childbearing potential not using 2 forms of contraception. Demonstrated hypersensitivity (eg, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis)

Precautions

Potential for human birth defects Analog of thalidomide, a known human teratogen that causes severe, life-threatening human birth defects. Avoid during pregnancy; if taken during pregnancy, likely to cause birth defects or fetal death. Pregnancy test is required prior initiation of therapy and should commence contraceptive measures following negative result. Pregnancy test must be repeated at a regular interval during therapy. History of thrombosis; smokers; patients w/ HTN, hyperlipidaemia, high tumour burden. Renal impairment. Significantly increased risk of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as risk of myocardial infarction and stroke in patients with multiple myeloma receiving lenalidomide with dexamethasone. Lactation: discontinue drug or do not nurse

Pregnancy-Lactation

Interactions

May increase risk of thrombosis w/ erythropoietic agents. May increase plasma concentration of digoxin, ketoconazole, itraconazole, ciclosporin, verapamil, quinidine, clarithromycin.

Adverse Effects

Side effects of Lenalidomide : >10% Thrombocytopenia (62%),Neutropenia (59%),Diarrhea (48%),Pruritus (42%),Nausea (35%),Rash (35%),Fatigue (31%),Constipation (24%),Arthralgia (22%),Back pain (21%),Peripheral edema (21%),Pyrexia (21%),Dizziness (20%),Headache (20%),Cough (19%),Muscle cramp (18%),Dyspnea (17%),URTI (15%),Anemia (12%),Pneumonia (12%),UTI (11%) 1-10% (critical AEs) Tumor flare reaction - MCL (10%),Abdominal pain (8%),Leukopenia (8%),Myalgia (8%),Pain (7%),Bronchitis (6%),Rhinitis (6%),Febrile neutropenia (5%),Peripheral neuropathy (5%) Potentially Fatal: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioedema. Acute hepatic failure; toxic, cytolytic, cholestatic and mixed cytolytic/ cholestatic hepatitis.

Mechanism of Action

Lenalidomide, a thalidomide analogue, is an immunomodulatory agent w/ antiangiogenic and antineoplastic property. It inhibits proinflammatory cytokines secretion, increases interleukin-2 and interferon-γ secretion, and increases cytolytic T-cell and natural killer cell response. It also inhibits the growth of myeloma cells by inducing cell cycle arrest and cell death.