CHENODIOL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CHENODIOL (CHENODIOL).
Chenodiol is a bile acid that reduces cholesterol saturation in bile by suppressing hepatic synthesis of cholesterol and inhibiting intestinal absorption of cholesterol. It also expands the bile acid pool and decreases biliary cholesterol secretion, promoting dissolution of cholesterol gallstones.
| Metabolism | Chenodiol is conjugated with glycine or taurine in the liver; undergoes enterohepatic circulation; metabolized by gut microbiota to lithocholic acid, which is partially absorbed and conjugated in the liver. |
| Excretion | Primarily biliary (renal excretion minimal; <1% unchanged in urine). Fecal excretion as metabolites. |
| Half-life | Terminal elimination half-life: 3-5 days. Clinical context: Prolonged due to enterohepatic recycling; steady-state achieved in 3-4 weeks. |
| Protein binding | >95% bound to plasma proteins (primarily albumin and low-density lipoproteins). |
| Volume of Distribution | Approximately 0.2-0.3 L/kg. Clinical meaning: Limited to extracellular fluid and liver; reflects hepatic uptake and biliary secretion. |
| Bioavailability | Oral: ~80-90% absorbed; first-pass extraction by liver reduces systemic bioavailability to 50-60%. |
| Onset of Action | Oral: 1-3 weeks for initial reduction of biliary cholesterol saturation; 6-12 weeks for radiographic gallstone dissolution. |
| Duration of Action | Clinical effect persists for months after discontinuation; gallstone dissolution requires 6-24 months of continuous therapy. Recurrence possible if treatment stopped prematurely. |
| Molecular Weight | 392.57 |
13-15 mg/kg/day orally in 2-4 divided doses, typically starting at 250 mg twice daily, then increasing by 250 mg/day every 1-2 weeks to full dose.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment recommended for mild-moderate renal impairment. Use caution in severe renal impairment (eGFR <30 mL/min/1.73m²) due to limited data. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% or consider alternative. Child-Pugh Class C: Contraindicated. |
| Pediatric use | Not approved for use in pediatric patients. Safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; start at lower end of dosing range and monitor renal function. |
| 1st trimester | Chenodiol is teratogenic in animal studies; avoid use in pregnancy. Adequate human studies are lacking. |
| 2nd trimester | Insufficient data for safety; possible fetal harm based on animal data. Use only if benefit outweighs risk. |
| 3rd trimester | Avoid use due to potential fetal toxicity and lack of safety data. |
Clinical note
Comprehensive clinical and safety monograph for CHENODIOL (CHENODIOL).
| Placental transfer | Chenodiol crosses the placenta in animals; extent in humans unknown. Likely significant due to low molecular weight. |
| Breastfeeding | Chenodiol may be excreted in breast milk; effects on nursing infants are unknown. Consider risk-benefit; alternative agents preferred. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to chenodiol or bile acidsSevere hepatic impairmentActive inflammatory bowel diseaseNon-functioning gallbladderCalcified gallstonesPregnancy
| Precautions | Hepatotoxicity: can cause dose-related hepatotoxicity, monitor liver function tests. Diarrhea: common dose-limiting adverse effect. May increase lithocholic acid levels, which is potentially hepatotoxic. Use with caution in patients with inflammatory bowel disease or colitis. |
| Food/Dietary | No specific food restrictions, but high-cholesterol diets may reduce efficacy. Avoid excessive alcohol intake as it may increase hepatotoxicity risk. |
Loading safety data…
| L3 (Moderately Safe) - Limited data suggest no significant risk but caution advised. |
| Teratogenic Risk | FDA Category X. Chenodiol is contraindicated in pregnant women. First trimester: risk of fetal hepatotoxicity and embryocidal effects based on animal studies; human data are lacking but potential for fetal harm is high. Second and third trimesters: unknown risk, but given drug's mechanism, fetal liver toxicity is possible. Use only if clearly needed and no alternative. |
| Fetal Monitoring | Pregnancy test before initiation and monthly during treatment. Monitor liver function tests (ALT, AST, alkaline phosphatase, bilirubin) and serum lipids every 1-3 months. For fetal: serial ultrasound for growth and morphology if inadvertent exposure occurs. |
| Fertility Effects | No known direct effect on fertility. However, due to teratogenicity, women of childbearing potential must use effective contraception during therapy and for 1 month after discontinuation. |
| Clinical Pearls |
| Chenodiol (chenodeoxycholic acid) is a bile acid used for dissolution of radiolucent cholesterol gallstones in patients with a functioning gallbladder. It is reserved for those who are poor surgical candidates. Monitor liver function tests (LFTs) and serum lipids periodically; may cause dose-dependent hepatotoxicity and hypertriglyceridemia. Efficacy limited to small (<1.5 cm), floating, radiolucent stones. Therapy may require up to 24 months. Discontinue if no response after 12 months. |
| Patient Advice | Take exactly as prescribed, usually in divided doses with meals. · Complete the full course of therapy; gallstone dissolution may take months. · Report any new or worsening abdominal pain, jaundice, or diarrhea. · Avoid alcohol and hepatotoxic medications during treatment. · Attend scheduled blood tests to monitor liver function and cholesterol. |