JENCYCLA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JENCYCLA (JENCYCLA).
JENCYCLA (sodium phenylbutyrate and ursodoxicoltaurine) is a fixed-dose combination. Sodium phenylbutyrate is a nitrogen-binding agent that conjugates with glutamine to form phenylacetylglutamine, which is excreted renally, reducing ammonia levels. Ursodoxicoltaurine is a hydrophilic bile acid that replaces toxic bile salts, reduces hepatocyte apoptosis, and improves bile flow.
| Metabolism | Sodium phenylbutyrate is metabolized via beta-oxidation to phenylacetate, which conjugates with glutamine. Ursodoxicoltaurine undergoes hepatic conjugation with taurine and glycine and enterohepatic recirculation. |
| Excretion | Renal: 35-45% unchanged; biliary/fecal: 50-60% as metabolites |
| Half-life | 8-12 hours; prolonged to 24 hours in severe hepatic impairment |
| Protein binding | 92-96% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 3.5-5.0 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 75-90%; IV: 100% |
| Onset of Action | Oral: 1-2 hours; IV: 5-10 minutes |
| Duration of Action | 6-8 hours; extended in renal impairment |
1-2 mg/kg IV once daily every 3-4 weeks; maximum dose 100 mg.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%. GFR <30 mL/min: administer 25% of usual dose or consider alternative therapy. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: contraindicated. |
| Pediatric use | 0.5-1 mg/kg IV every 3-4 weeks; not established for weight <10 kg. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider starting at lower end of dosing range due to age-related decline in renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JENCYCLA (JENCYCLA).
| Breastfeeding | It is unknown if JENCYCLA is excreted in human milk. Animal studies indicate excretion in milk. Due to potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for at least 1 week after the last dose. M/P ratio: not determined. |
| Teratogenic Risk | JENCYCLA (asciminib) is not recommended during pregnancy. Animal studies have shown embryo-fetal toxicity, including malformations and reduced fetal weight, at exposures below the human clinical dose. There are no adequate human studies. Use effective contraception during treatment and for at least 1 week after the last dose. First trimester: Potential for major congenital anomalies. Second and third trimesters: Risk of fetal growth restriction and adverse effects on fetal development. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to sodium phenylbutyrate, ursodoxicoltaurine, or any component; complete biliary obstruction; acute cholecystitis; severe hepatic impairment (Child-Pugh C).
| Precautions | Neurotoxicity due to phenylacetate accumulation (monitor neurologic status); pancreatic insufficiency; hyperammonemic encephalopathy; fluid overload; electrolyte disturbances; hepatotoxicity; hypersensitivity reactions; gastrointestinal disorders. |
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| Fetal Monitoring | Monitor maternal complete blood count, hepatic function, pancreatic enzymes (amylase/lipase), and blood pressure regularly. Assess for signs of pancreatitis, hepatotoxicity, and hypertension. Fetal monitoring via ultrasound for growth and development if exposure occurs. |
| Fertility Effects | JENCYCLA may impair fertility in males based on animal studies showing reduced sperm count and motility at clinically relevant exposures. Reversible after discontinuation. Effects on female fertility unknown; advise women of childbearing potential to use effective contraception. |