LENALIDOMIDE
Clinical safety rating
cautionComprehensive clinical and safety monograph for LENALIDOMIDE (LENALIDOMIDE).
Immunomodulatory agent with anti-angiogenic and anti-proliferative properties; alters cytokine production, enhances T-cell and NK-cell activity, inhibits tumor angiogenesis, and directly induces apoptosis in tumor cells.
| Metabolism | Metabolized via hydrolysis and glucuronidation; CYP450 enzymes play a minor role. |
| Excretion | Renal: ~82% unchanged; fecal <5%; biliary negligible. |
| Half-life | Terminal half-life ~3 hours (range 2-5 h) in multiple myeloma patients; prolongation in renal impairment requires dose adjustment. |
| Protein binding | ~30% bound, primarily to albumin. |
| Volume of Distribution | Approximately 0.6 L/kg (range 0.4-0.8 L/kg), indicating distribution into total body water. |
| Bioavailability | Oral: ~80% (range 60-100%); food does not significantly affect absorption. |
| Onset of Action | Oral: 2-4 weeks for initial clinical response in multiple myeloma; maximal response may take 3-6 months. |
| Duration of Action | Duration varies with dosing schedule; continuous daily dosing with 21/28 day cycles; effects diminish after discontinuation. |
| Molecular Weight | 259.3 |
10 mg orally once daily on days 1-21 of 28-day cycle for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes; 25 mg orally once daily on days 1-21 of 28-day cycle for relapsed/refractory multiple myeloma.
| Dosage form | CAPSULE |
| Renal impairment | For CrCl 30-60 mL/min: 5 mg once daily; for CrCl <30 mL/min not requiring dialysis: 2.5 mg once daily; for CrCl <30 mL/min requiring dialysis: 2.5 mg once daily post-dialysis on dialysis days. |
| Liver impairment | No specific dose adjustment for hepatic impairment in FDA labeling; use with caution in severe hepatic impairment (Child-Pugh C) due to lack of data. |
| Pediatric use | Not approved in pediatric patients; safety and efficacy not established in patients <18 years. |
| Geriatric use | No specific dose adjustment beyond renal function; monitor for hematologic toxicity and thromboembolic events due to age-related comorbidities and renal impairment. |
| 1st trimester | Contraindicated. Severe teratogen causing multiple congenital malformations (e.g., phocomelia). Use only if effective contraception is used. |
| 2nd trimester | Contraindicated. Fetal toxicity and teratogenicity continue; risk of severe malformations. |
| 3rd trimester | Contraindicated. Risk of fetal harm and potential for neonatal complications. |
Clinical note
Comprehensive clinical and safety monograph for LENALIDOMIDE (LENALIDOMIDE).
| Placental transfer | Extensive; crosses placenta readily in animal models and humans. Known human teratogen. |
| Breastfeeding | Excretion into human milk unknown. Due to potential for serious adverse reactions in nursing infants, breastfeeding should be avoided during therapy and for at least 1 week after last dose. |
| Lactation Rating | L5 |
| Teratogenic Risk | Lenalidomide is a thalidomide analogue; it is teratogenic in humans. Pregnancy category X. In the first trimester, there is a high risk of severe birth defects (e.g., limb defects, cardiac anomalies) and fetal death. No adequate studies in second or third trimester, but risk persists throughout pregnancy. Contraindicated in pregnancy. |
| Fetal Monitoring | All females of reproductive potential must undergo pregnancy testing prior to therapy (negative serum pregnancy test with sensitivity at least 25 mIU/mL), then weekly during first month, then every 2-4 weeks thereafter. Use two forms of effective contraception or complete abstinence. Monitor for fetal exposure; if pregnancy occurs, discontinue drug immediately and refer to obstetrician. |
| Fertility Effects | Lenalidomide may impair fertility in males and females. In males, it may reduce sperm count and motility; reversible upon discontinuation. In females, may cause ovarian failure or menstrual irregularities. Advise patients of potential impact on future fertility. |
■ FDA Black Box Warning
Embryo-fetal toxicity: Can cause fetal harm. Do not use during pregnancy. Females of reproductive potential must use contraception or abstain. Hematologic toxicity: Significant neutropenia and thrombocytopenia; monitor blood counts. Deep vein thrombosis and pulmonary embolism: Increased risk; monitor and consider prophylaxis.
| Common Effects | Headache Nausea Rash Breathlessness Dizziness Fatigue Decreased white blood cell count neutrophils Joint pain Itching Diarrhea Low blood platelets Peripheral edema Cough Back pain Upper respiratory tract infection Decreased appetite Nasopharyngitis inflammation of the throat and nasal passages |
| Serious Effects |
PregnancyWomen of childbearing potential not using effective contraceptionHypersensitivity to lenalidomide or any component
| Precautions | Hematologic toxicity (neutropenia and thrombocytopenia); thromboembolic events; hepatotoxicity; allergic reactions; tumor lysis syndrome; thyroid disorders; neuropathy; increased risk of second primary malignancies. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges (including marmalade) as they inhibit CYP3A4 and may increase lenalidomide exposure. No other significant food interactions. Take capsules with water; do not crush or chew. |
| Clinical Pearls | Lenalidomide is an immunomodulatory drug (IMiD) with anti-angiogenic and anti-proliferative properties. It requires risk evaluation and mitigation strategy (REMS) due to teratogenicity. Monitor for thromboembolic events (DVT/PE) especially when combined with dexamethasone. Consider dose adjustment for renal impairment (CrCl < 60 mL/min). Baseline and periodic monitoring of CBC, thyroid function, and liver enzymes is essential. May cause tumor lysis syndrome in high tumor burden patients; ensure hydration and prophylaxis. |
| Patient Advice | Do not take lenalidomide if you are pregnant, breastfeeding, or planning to become pregnant; use two reliable forms of contraception during treatment and for 4 weeks after stopping. · Do not donate blood or sperm while taking lenalidomide and for 4 weeks after discontinuation. · Report any symptoms of blood clots (swelling, pain, redness in leg, sudden chest pain, shortness of breath) or signs of infection (fever, chills) immediately. · Take lenalidomide exactly as prescribed, usually once daily with a glass of water; do not break, chew, or open capsules. · Avoid grapefruit, grapefruit juice, and Seville oranges as they may affect drug metabolism. · Keep all appointments for blood tests to monitor for low blood cell counts and other side effects. |
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