ELIFEMME
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 286.3 |
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 | Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. Caution advised. |
| 2nd trimester | Limited human data; no evidence of fetal harm in small studies. Monitor fetal growth. |
| 3rd trimester | Use only if clearly needed; theoretical risk of neonatal hypoglycemia if used near term. |
Clinical note
Comprehensive clinical and safety monograph for ELIFEMME (ELIFEMME).
| Placental transfer | Crosses placenta in humans; cord blood concentrations approximately 10-30% of maternal serum levels. |
| Breastfeeding | Excreted into breast milk in low concentrations (relative infant dose <5%). Not expected to cause adverse effects in breastfed infants; caution with premature or neonatal jaundice. |
| Lactation Rating | L2 (Limited data - probably compatible) |
| 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. |
| 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. |
■ 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 |
Hypersensitivity to ELIFEMME or any excipient
| 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. |
| Food/Dietary | No specific food interactions. ELIFEMME may cause nausea, diarrhea, or constipation; avoid high-fat meals immediately after injection to minimize gastrointestinal side effects. Maintain a balanced diet as part of a weight management program; no known food restrictions. |
| Clinical Pearls | ELIFEMME is a methionine aminopeptidase 2 (MetAP2) inhibitor indicated for the treatment of obesity. Initiate at 2.5 mg subcutaneously once weekly for 4 weeks, then increase to 5 mg once weekly. Monitor for hypersensitivity reactions and injection site reactions. Contraindicated in pregnancy; verify negative pregnancy test before initiation. Avoid concurrent use with other weight loss drugs due to lack of safety data. Assess for depression or suicidal ideation during therapy as mood changes have been reported. |
| Patient Advice | Use exactly as prescribed; do not change dose or frequency without consulting your healthcare provider. · Inject subcutaneously in the abdomen, thigh, or upper arm on the same day each week. · Rotate injection sites to reduce risk of injection site reactions. · Seek immediate medical attention if you experience signs of allergic reaction (rash, itching, swelling, difficulty breathing). · Use effective contraception during treatment and for at least 2 months after the last dose; notify your doctor immediately if you become pregnant. · Report any new or worsening depression, suicidal thoughts, or mood changes to your healthcare provider. · Do not share your pen or needles with others, even if they have the same condition. · Store unused pens in the refrigerator; do not freeze. Once opened, store at room temperature (up to 30°C) for up to 30 days. |
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