Lenalidomide

(BAN, USAN, rINN)
Lenalidomide Chemical formula
Synonyms: CC-5013; CDC-501; Lénalidomide; Lenalidomidum. 3-(4-Amino-1-oxo-1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione.
Cyrillic synonym: Леналидомид.

💊 Chemical information

Chemical formula: C13H13N3O3 = 259.3.
CAS — 191732-72-6.
ATC — L04AX04.
ATC Vet — QL04AX04.

💊 Adverse Effects, Treatment, and Precautions

Lenalidomide is associated with significant neutropenia and thrombocytopenia. Anaemia is also common. Patients may require dose reduction or therapy may need to be delayed or stopped. Full blood counts should be monitored weekly for the first 8 weeks of therapy, and monthly thereafter. There is also an increased risk of deep-vein thrombosis and pulmonary embolism with lenalidomide. Other adverse effects include gastrointestinal disturbances, pruritus, rash, and fatigue. Dyspnoea, muscle cramps, hypotension, tremor, hypoaesthesia, and infections such as pneumonia are common. Peripheral neuropathy has been reported, as have cases of hypothyroidism; thyroid function should be monitored. Cardiac disorders and hepatotoxicity have also been reported. Caution is advised in patients with renal impairment as lenalidomide is excreted via the kidneys. Because of potential teratogenicity lenalidomide use is restricted in women of child-bearing potential, see also under Thalidomide.

💊 Interactions

Lenalidomide may increase peak plasma concentrations of digoxin. Epoetins or other drugs that increase the risk of thrombosis should be used with caution in patients taking lenalidomide.

💊 Pharmacokinetics

Lenalidomide is rapidly absorbed with maximum plasma concentrations occurring between about 0.6 and 1.5 hours after an oral dose. Giving lenalidomide with food may reduce plasma concentrations but not the extent of absorption. Binding to plasma proteins is about 30%. About two-thirds of a dose is eliminated unchanged through the kidneys. The elimination halflife is about 3 hours after a 5 mg-dose; half-life increases with dose. Clearance decreases proportionally with renal function.

💊 Uses and Administration

Lenalidomide is an analogue of thalidomide that has immunomodulatory and antiangiogenic properties. It is given orally for the treatment of patients with transfusion-dependent anaemia due to myelodysplastic syndromes associated with certain abnormalities of chromosome 5 (deletion 5q abnormalities). The recommended initial dose is 10 mg daily. Lenalidomide is also used orally with dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. The recommended starting dose of lenalidomide is 25 mg daily, given for 21 days of a 28-day cycle. The recommended oral dose of dexamethasone is 40 mg daily on days 1 to 4, days 9 to 12, and days 17 to 20 of each 28-day cycle, for the first 4 cycles, and then 40 mg daily on days 1 to 4 of each 28-day cycle thereafter. Lenalidomide is associated with significant neutropenia and thrombocytopenia, and dosage is adjusted according to haematological toxicity.
1. List A, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005; 352: 549–57
2. Anderson KC. Lenalidomide and thalidomide: mechanisms of action—similarities and differences. Semin Hematol 2005; 42 (suppl 4): S3–S8
3. Hideshima T, et al. Current therapeutic uses of lenalidomide in multiple myeloma. Expert Opin Invest Drugs 2006; 15: 171–9
4. List A, et al. Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006; 355: 1456–65
5. Shah SR, Tran TM. Lenalidomide in myelodysplastic syndrome and multiple myeloma. Drugs 2007; 67: 1869–81
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7. Lacy MQ, et al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clin Proc 2007; 82: 1179–84
8. Dimopoulos M, et al. Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 2007; 357: 2123–32
9. Weber DM, et al. Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007; 357: 2133–42
10. Chanan-Khan AA, Cheson BD. Lenalidomide for the treatment of B-cell malignancies. J Clin Oncol 2008; 26: 1544–52.

Administration in

renal impairment. Lenalidomide is eliminated mainly via the kidneys as unchanged drug. Clearance decreases as renal function decreases, prolonging the elimination half-life and increasing exposure to the drug. A study recommended that dose adjustments be made for patients with creatinine clearance (CC) less than 50 mL/minute; a 40% reduction to 60% of the starting dose was recommended for these patients. For those with CC less than 30 mL/minute, the reduced dose should be given at extended dosing intervals. About 30% of circulating lenalidomide was removed by a 4-hour session of haemodialysis.1 UK licensed product information makes the following recommendations at the start of oral therapy for patients with multiple myeloma and renal impairment:
mild renal impairment (CC greater than or equal to 50 mL/minute): 25 mg once daily (full dose)
moderate renal impairment (CC from 30 mL/minute to less than 50 mL/minute): 10 mg once daily. This dose may be increased to 15 mg once daily after 2 cycles if the patient is not responding to treatment, but is tolerating lenalidomide
severe renal impairment (CC less than 30 mL/minute, not requiring dialysis): 15 mg every other day
end-stage renal disease (CC less than 30 mL/minute, requiring dialysis): 15 mg, three times weekly, after dialysis
1. Chen N, et al. Pharmacokinetics of lenalidomide in subjects with various degrees of renal impairment and in subjects on hemodialysis. J Clin Pharmacol 2007; 47: 1466–75.

💊 Preparations

Proprietary Preparations

Cz.: Revlimid; Fr.: Revlimid; Port.: Revlimid; UK: Revlimid; USA: Revlimid.
Published January 17, 2019.