POMBILITI
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 493.6 |
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 | No adequate human data; animal studies suggest risk. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Limited data; potential for fetal harm. Use only if clearly needed. |
| 3rd trimester | May cause fetal harm; avoid near term due to risk of neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for POMBILITI (POMBILITI).
| Placental transfer | Highly likely based on molecular weight and lipophilicity; crosses placenta in animal studies. |
| Breastfeeding | Not recommended during breastfeeding due to potential for serious adverse reactions in nursing infants. Consider alternative therapies. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to pombiliti or any excipientSevere hepatic impairmentPregnancy (unless benefit outweighs risk)
| 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). |
| Food/Dietary | No known food interactions. Maintain a balanced diet as recommended by a healthcare provider. There are no specific dietary restrictions required with Pombiliti. |
| Clinical Pearls | Pombiliti (cipaglucosidase alfa) is a recombinant human acid alpha-glucosidase (GAA) enzyme replacement therapy for Pompe disease. Do not confuse with alglucosidase alfa (Myozyme/Lumizyme). Requires premedication with antihistamines and antipyretics due to risk of infusion-associated reactions (IARs). Monitor for anaphylaxis, particularly during initial infusions. Administer by IV infusion over approximately 4 hours. Use a low-protein-binding infusion set with an in-line low-protein-binding filter. May cause rapid deterioration in patients with cardiac hypertrophy; monitor cardiac function before and during treatment. |
| Patient Advice | Inform your healthcare provider immediately if you experience hives, itching, difficulty breathing, swelling, chest tightness, or fever during or after the infusion. · You may receive premedications (such as antihistamines and acetaminophen) before your infusion to reduce the risk of allergic reactions. · Do not miss your scheduled infusions; regular treatment is necessary to manage Pompe disease. · Report any new or worsening muscle weakness, breathing difficulties, or heart-related symptoms. · Keep a list of all medications you take, including over-the-counter drugs and supplements, and share it with your doctor. · Pombiliti is not a cure; it is an enzyme replacement therapy to reduce symptoms and slow disease progression. |
Loading safety data…