POMBILITI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for POMBILITI (POMBILITI).
POMBILITI (elafibranor) is a dual peroxisome proliferator-activated receptor (PPAR) alpha/delta agonist that modulates lipid metabolism, inflammation, and fibrosis pathways. It reduces hepatic steatosis, inflammation, and ballooning by increasing fatty acid oxidation and decreasing lipogenesis.
| Metabolism | Primarily metabolized by CYP3A4, CYP2C8, and CYP2C9; also undergoes glucuronidation. The active metabolite, GFT505, is formed via hydrolysis. |
| Excretion | Primarily biliary-fecal (77% of absorbed dose) and renal (23% unchanged) with enterohepatic recirculation. |
| Half-life | Terminal elimination half-life is approximately 11 hours (range 6.5–19 h). Clinical context: supports twice-daily dosing with moderate accumulation; half-life prolonged in hepatic impairment. |
| Protein binding | >99% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 2000 L (>25 L/kg), indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral bioavailability is approximately 25% (range 15–35%) due to first-pass metabolism; may increase with high-fat meal. |
| Onset of Action | Oral: Onset of clinical effect occurs within 2–4 hours after dosing; maximal effect observed at 4–6 hours. |
| Duration of Action | Duration of action is approximately 12 hours based on pharmacodynamic effects; clinical note: consistent with BID dosing and sustained receptor occupancy for at least 12 h. |
500 mg orally twice daily
| Dosage form | INJECTABLE |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR 15-29 mL/min: 250 mg twice daily; GFR <15 mL/min or dialysis: 250 mg once daily |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 250 mg twice daily; Child-Pugh C: not recommended |
| Pediatric use | Weight <40 kg: 10 mg/kg orally twice daily (max 500 mg/dose); Weight ≥40 kg: 500 mg twice daily |
| Geriatric use | No specific adjustment required; monitor renal function and consider age-related decline in GFR |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for POMBILITI (POMBILITI).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Due to potential for serious adverse reactions (e.g., immunosuppression, myelosuppression), breastfeeding is not recommended during therapy and for at least 3 months after last dose. |
| Teratogenic Risk | Pombiliti is contraindicated in pregnancy. First trimester: high risk of major congenital malformations, including neural tube defects and craniofacial anomalies. Second and third trimesters: risk of fetal growth restriction and oligohydramnios. Animal studies show embryolethality and teratogenicity at subclinical doses. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to elafibranor or any component of the formulation.","Severe hepatic impairment (Child-Pugh class C)."]
| Precautions | ["Hepatotoxicity: Elevations in liver enzymes have been reported; monitor liver function tests before and during treatment.","Myopathy: Risk of muscle injury; assess creatine kinase if muscle symptoms occur.","Gallbladder-related events: Increased risk of cholelithiasis and cholecystitis.","Fetal risk: Based on animal data, may cause fetal harm; advise effective contraception in females of reproductive potential.","Renal impairment: Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²)."] |
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| Fetal Monitoring |
| For women of childbearing potential: confirm negative pregnancy test before initiation; use effective contraception during and for 6 months after therapy. Monitor for fetal growth restriction via ultrasound if inadvertent exposure occurs. No specific maternal monitoring beyond standard oncology surveillance. |
| Fertility Effects | Women: may cause amenorrhea and premature ovarian failure due to gonadotoxicity; human data suggest reduced fertility. Men: may cause oligospermia or azoospermia; recovery unknown. Preclinical studies show testicular damage. Fertility preservation counseling recommended before treatment. |