BLACK BOX WARNING
- embryo-fetal toxicity — mandatory REMS program (REVLIMID REMS)
- venous and arterial thromboembolism
- hematologic toxicity
lenalidomide
Brand: Revlimid
⚠ BBW ISMP High Alert Prototype: thalidomide
Drug Class: immunomodulatory imide drug (IMiD)
Drug Family: antineoplastic
Subclass: thalidomide analog with improved efficacy and safety
Organ Systems: hematology-oncologyimmunology
Mechanism of Action
Binds cereblon (CRBN), a component of a CRL4 E3 ubiquitin ligase complex; redirects ubiquitin ligase to degrade two transcription factors (Ikaros/IKZF1 and Aiolos/IKZF3) that are essential for myeloma cell survival; also has direct anti-angiogenic, anti-proliferative, and immunostimulatory effects.
cereblon (CRBN) E3 ubiquitin ligase complex
Indications
- multiple myeloma (with dexamethasone or with bortezomib+dexamethasone)
- myelodysplastic syndrome (5q deletion — del(5q) MDS)
- mantle cell lymphoma (maintenance after autologous HSCT)
- follicular lymphoma
Contraindications
- pregnancy (severe teratogen — thalidomide analog)
- hypersensitivity to thalidomide or lenalidomide
Adverse Effects
Common
- myelosuppression (neutropenia, thrombocytopenia)
- diarrhea
- fatigue
- rash
Serious
- venous thromboembolism (DVT/PE — requires thromboprophylaxis)
- severe myelosuppression
- teratogenicity (phocomelia)
- peripheral neuropathy (less than thalidomide)
- second primary malignancies
- tumor flare reaction
Pharmacokinetics (ADME)
| Absorption | 25–30% oral bioavailability |
| Distribution | moderate distribution; crosses placenta |
| Metabolism | minimal; two metabolites with <10% of parent activity |
| Excretion | renal (80% unchanged); dose adjustment required in CKD |
| Half-life | 3–5 hours |
| Onset | days |
| Peak | 0.6–1.5 hours |
| Duration | daily (21 or 28 days per cycle) |
| Protein Binding | 30% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| erythropoietin/darbepoetin | additive thrombosis risk — increase DVT/PE incidence in myeloma; avoid combination without anticoagulation | major |
| digoxin | lenalidomide may increase digoxin levels via P-gp inhibition | moderate |
Nursing Considerations
- REMS program participation is MANDATORY for prescribers, dispensing pharmacists, and patients; no prescription can be filled without confirmation of REMS enrollment and negative pregnancy test.
- Mandatory thromboprophylaxis: all patients receiving lenalidomide with dexamethasone require aspirin (low risk) or therapeutic anticoagulation (LMWH or warfarin for high-risk patients).
- Monitor CBC every 2 weeks for the first 12 weeks; lenalidomide causes significant neutropenia and thrombocytopenia.
- Reiterate pregnancy avoidance counseling at every encounter; women must have two negative pregnancy tests before initiating and monthly during therapy.
Clinical Pearls
- Lenalidomide's mechanism (cereblon-mediated targeted protein degradation) established the PROTAC (proteolysis-targeting chimera) concept in cancer biology — directing the cell's own ubiquitin-proteasome system to degrade specific oncoproteins.
- The REVLIMID REMS program is one of the most restrictive in U.S. pharmaceutical history, requiring mandatory prescriber certification, patient enrollment, negative pregnancy tests before each cycle, and direct dispensing through certified pharmacies — a regulatory framework driven by the thalidomide disaster.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.