REVLIMID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REVLIMID (REVLIMID).
Revlimid (lenalidomide) is an immunomodulatory agent with antiangiogenic and antineoplastic properties. It inhibits tumor necrosis factor-alpha, stimulates T-cell proliferation and IL-2 production, and inhibits angiogenesis by blocking VEGF and bFGF. It also modulates the ubiquitin E3 ligase cereblon, leading to degradation of transcription factors Ikaros and Aiolos, which results in direct tumor cell apoptosis and enhanced immune function.
| Metabolism | Lenalidomide is primarily metabolized via hydrolysis, with minor involvement of CYP1A2 and CYP3A4. The major route of elimination is renal excretion of unchanged drug; approximately 67% of the dose is excreted unchanged in urine. |
| Excretion | Primarily renal excretion as unchanged drug (approximately 67% of the dose in urine over 24 hours) with minor fecal elimination (<4%). |
| Half-life | Terminal elimination half-life of approximately 3-5 hours in patients with normal renal function. Half-life is prolonged in renal impairment (up to 9 hours in severe impairment). |
| Protein binding | Approximately 30% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 0.6-1.0 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Absolute oral bioavailability is approximately 33% (range 20-50%) due to first-pass metabolism. Food does not significantly alter bioavailability. |
| Onset of Action | Clinical effects (e.g., reduction in tumor markers, hematologic improvement) may be observed within 2-4 weeks of oral administration. |
| Duration of Action | Duration of clinical effect is continuous with daily dosing; sustained response requires ongoing therapy. Cytopenias and thromboembolic risk persist throughout treatment. |
5-10 mg orally once daily for 21 days of a 28-day cycle; dose depends on indication (e.g., 10 mg for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes).
| Dosage form | CAPSULE |
| Renal impairment | For CrCl ≥60 mL/min: start at 10 mg daily; CrCl 30-60 mL/min: start at 5 mg daily; CrCl <30 mL/min: 5 mg every other day; for dialysis patients: 5 mg three times weekly after dialysis. |
| Liver impairment | No specific Child-Pugh based dose adjustments provided in labeling; use caution and monitor for toxicity in hepatic impairment. |
| Pediatric use | Safety and efficacy not established; not recommended for pediatric use outside clinical trials. |
| Geriatric use | No specific dose adjustment based solely on age; monitor renal function and adjust per renal guidelines as elderly often have decreased CrCl. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REVLIMID (REVLIMID).
| Breastfeeding | It is unknown if lenalidomide is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated. M/P ratio is not available. |
| Teratogenic Risk | REVLIMID (lenalidomide) is an analog of thalidomide, a known human teratogen. It is absolutely contraindicated in pregnancy. Fetal exposure can cause severe, life-threatening birth defects including limb reduction, cardiac anomalies, and neural tube defects. Risk is highest during the first trimester but extends throughout gestation. |
■ FDA Black Box Warning
Revlimid (lenalidomide) can cause fetal harm. Women of childbearing potential must use effective contraception and undergo pregnancy testing prior to and during therapy. There is an increased risk of venous thromboembolism, including deep vein thrombosis and pulmonary embolism. The drug is contraindicated in pregnant women.
| Serious Effects |
["Pregnancy (due to teratogenicity)","Women of childbearing potential not using effective contraception","Hypersensitivity to lenalidomide or any component of the formulation"]
| Precautions | ["Hematologic toxicity: Neutropenia and thrombocytopenia are common, requiring dose adjustments.","Thromboembolism: Increased risk of DVT, PE, and stroke; consider prophylactic anticoagulation or antiplatelet therapy.","Second primary malignancies: Risk of development of other cancers (e.g., AML, MDS) in patients receiving lenalidomide.","Hepatotoxicity: Elevations of liver enzymes have been reported.","Allergic reactions: Including angioedema and Stevens-Johnson syndrome.","Renal impairment: Requires dose adjustment; monitor renal function."] |
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| Fetal Monitoring |
| There is no safe monitoring; pregnancy must be excluded before treatment. Females of reproductive potential must use two reliable forms of contraception for 4 weeks before, during, and for 4 weeks after therapy. Pregnancy tests are required weekly for first 4 weeks, then every 2-4 weeks thereafter. |
| Fertility Effects | Lenalidomide may impair fertility in males and females based on animal studies. Reversible effects on spermatogenesis have been observed. In females, it may cause menstrual irregularities and ovarian suppression. |