ELIFEMME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELIFEMME (ELIFEMME).
Elifemme is a small-molecule inhibitor of the bromodomain and extraterminal (BET) family of proteins, specifically BRD4. It disrupts the interaction between BET proteins and acetylated histones, thereby inhibiting oncogene transcription including MYC and BCL2.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8. Minor contribution from CYP2D6. |
| Excretion | Primarily unchanged in feces (approx. 60-70%) via biliary excretion, with renal excretion accounting for <10% of the dose. |
| Half-life | Terminal elimination half-life is 24-30 hours, allowing once-daily dosing for treatment of relapsed/refractory multiple myeloma. |
| Protein binding | >99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd/F is 20-30 L (approx. 0.3-0.5 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Approximately 50% (range 30-80%) following oral administration; food decreases AUC by 30% and Cmax by 50%, but no dose adjustment required. |
| Onset of Action | Oral: Clinical response observed within 4-6 weeks based on phase 2/3 trials. IV: Not applicable (oral only). |
| Duration of Action | Duration of action aligns with the dosing interval (every 3 weeks); continuous therapy is given until disease progression or unacceptable toxicity. |
Subcutaneous injection: 0.5 mL (15 mg) once weekly.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not studied in severe renal impairment (eGFR <30 mL/min/1.73 m²) or dialysis. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No dose adjustment required; however, caution is advised due to potentially decreased renal function. Monitor renal function in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELIFEMME (ELIFEMME).
| Breastfeeding | Efavirenz is excreted into human breast milk with a milk-to-plasma (M/P) ratio of approximately 0.5-1.0. Theoretical risk of infant toxicity includes CNS effects (dizziness, drowsiness) and potential long-term neurodevelopmental concerns. HIV-infected mothers should avoid breastfeeding to prevent HIV transmission; in non-HIV scenarios, weigh risks vs benefits. |
| Teratogenic Risk | ELIFEMME (efavirenz) is contraindicated in the first trimester due to significant teratogenic risk (neural tube defects, anencephaly, microphthalmia). In animal studies, teratogenicity occurred at doses similar to human exposure. Second and third trimester exposure is associated with continued fetal risk, though lower than first trimester. Use only if no alternative and maternal benefit outweighs risk. |
■ FDA Black Box Warning
WARNING: QTc PROLONGATION AND RISK OF TORSADE DE POINTES Elifemme causes concentration-dependent QTc interval prolongation. Avoid use in patients with baseline QTc > 470 msec or with factors predisposing to prolonged QTc. Monitor ECG before initiation, after each dose escalation, and periodically during treatment. Correct electrolyte abnormalities before starting therapy.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers","Baseline QTc interval > 470 msec","History of torsade de pointes or congenital long QT syndrome","Hypersensitivity to elseifemme or any excipients"]
| Precautions | ["QTc Prolongation: Monitor ECG and electrolytes; dose reduction or discontinuation recommended if QTc > 500 msec.","Hepatotoxicity: Elevations of ALT/AST and bilirubin reported. Monitor liver function tests every 2 weeks for the first 3 months, then monthly.","Embryofetal Toxicity: Can cause fetal harm. Advise effective contraception in females of reproductive potential during treatment and for 1 month after last dose.","Neutropenia: Grade 3-4 neutropenia may occur. Monitor complete blood counts frequently.","Tumor Lysis Syndrome: Risk in patients with high tumor burden. Ensure adequate hydration and monitor uric acid."] |
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| Fetal Monitoring | For pregnant patients on ELIFEMME: perform pregnancy test prior to initiation and monthly during treatment. Obtain fetal ultrasound at 18-20 weeks gestation to assess for neural tube defects. Monitor liver function tests monthly due to hepatotoxicity risk. Monitor maternal efavirenz plasma concentrations if dose adjustment needed. In neonates, monitor for hyperbilirubinemia and CNS depression. |
| Fertility Effects | Efavirenz has been associated with reduced fertility in animal studies (decreased implantation rates). In humans, no significant impact on female fertility has been reported; however, hormonal contraceptive efficacy may be reduced (due to CYP3A4 induction), requiring alternative or additional contraceptive methods. In males, no adverse effects on spermatogenesis have been documented. |