Version July 2025
Because of the potential hepatotoxicity of chenodiol, poor response rate in some subgroups of chenodiol treated patients, and an increased rate of a need of cholecystectomy in other chenodiol treated subgroups, chenodiol is not an appropriate treatment for many patients with gallstones. Chenodiol should be reserved for carefully selected patients and treatment must be accompanied by systematic monitoring for liver function alterations. Aspects of patient selection, response rates and risks versus benefits are given in the insert.
Dosage guidance:
Clinical considerations: Radiopaque (calcified or partially calcified) stones and bile pigment stones do not respond to bile acid dissolution therapy. Studies have shown dissolution rates are higher in patients with small (<15 mm in diameter), radiolucent, and/or floatable stones.
Cerebrotendinous xanthomatosis: Oral: 250 mg 3 times daily.
Gallstone dissolution (monotherapy): Oral: Initial: 250 mg twice daily for 2 weeks, then increase dose by 250 mg/day each week until the recommended maintenance dose or maximum tolerated dose is achieved; maintenance: 13 to 16 mg/kg/day in 2 divided doses. Note: Dosages <10 mg/kg are usually ineffective and may increase the risk of cholecystectomy. Discontinue treatment if there is no response by 18 months; safe use beyond 24 months has not been established.
Duration of therapy: Response to therapy should be monitored with oral cholecystograms or ultrasonograms at 6- to 9-month intervals. Complete dissolution should then be confirmed by a repeat test 1 to 3 months after continued therapy. If partial dissolution is not observed by 9 to 12 months, complete dissolution is unlikely. If no response is observed by 18 months, therapy should be discontinued; safety beyond 24 months of use has not been established.
Gallstone dissolution (combination therapy; off-label dose): Oral: 5 to 7.5 mg/kg/day once daily at bedtime, in combination with ursodeoxycholic acid, with or without adjuvant lithotripsy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
Liver impairment prior to treatment initiation:
Child-Turcotte-Pugh class A to C: There are no dosage adjustments provided in the manufacturer’s labeling; avoid use in patients with preexisting liver impairment. Contraindicated for use in presence of known hepatocyte dysfunction or bile duct abnormalities.
Liver impairment developing in patient already receiving chenodiol:
Chenodiol-induced liver injury:
Cerebrotendinous xanthomatosis: Aminotransferase level >3 times ULN or total bilirubin >2 times ULN: Temporarily withhold treatment; resume when aminotransferase levels return to normal.
Other indications:
Aminotransferase level 1.5 to 3 times ULN persisting for >3 to 6 months: Temporarily withhold treatment; resume when aminotransferase levels return to normal.
Aminotransferase level >3 times ULN: Discontinue treatment immediately.
Chenodal:
Diarrhea: Temporarily decrease dose; resume previous dose when diarrhea resolves. Discontinuation of therapy may be required for persistent diarrhea.
Increased cholesterol: Discontinue treatment if cholesterol increases above acceptable age-adjusted limit
(For additional information see "Chenodeoxycholic acid (chenodiol): Pediatric drug information")
Cerebrotendinous xanthomatosis: Limited data available: Infants, Children, and Adolescents: Oral: Usual dose: 10 to 15 mg/kg/day divided 1 to 3 times daily; maximum daily dose: 750 mg/day; in infants and young children, a lower dose of 5 mg/kg/day in 3 divided doses has been suggested by some experts (Ref).
Gallstone dissolution: Limited data available; not routinely used for cholelithiasis in pediatric patients; use has been replaced by other treatments (Ref): Children ≥12 years and Adolescents: Oral: 15 mg/kg/day divided 3 times daily with meals; dosing based on reported experience in three obese pediatric patients (age range: 12 to 13 years); Note: Not first-line therapy due to frequent side effects (eg, increased LFT, diarrhea) and other therapeutic options available (Ref).
Inborn errors of bile acid biosynthesis; steroid dehydrogenase or reductase deficiencies (susceptible) : Very limited data available:
Note: Due to the rarity of the disease states, data is limited to small case series and case reports. Adjust dose based upon targeted bile acid or biosynthesis intermediate compound concentrations. Combination therapy with ursodeoxycholic acid (ursodiol) dependent on specific deficiency, and phenotypic presentation of syndrome.
Infants, Children, and Adolescents: Oral: Usual initial range: 5 to 10 mg/kg/day divided once or twice daily; higher initial doses of 11 to 18 mg/kg/day have also been reported; a maintenance dose of 5 mg/kg/day was the most frequently reported and initiated once targeted bile acid normalized or stabilized (depending upon the syndrome) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in manufacturer's labeling.
Infants, Children, and Adolescents: Use extreme caution; contraindicated for use in presence of known hepatocyte dysfunction or bile duct abnormalities. A case report describes an infant who developed hepatoxicity during therapy (jaundice, hepatomegaly) at 15 mg/kg/day dose; chenodiol was discontinued until clinical parameters normalized, then restarted at a reduced dose (5 mg/kg/day) without recurrence of hepatotoxicity (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Hypertension
Gastrointestinal: Abdominal pain (including upper abdominal pain), constipation, diarrhea (30% to 40%)
Hepatic: Increased serum transaminases (transient: ≥30%; including increased serum alanine aminotransferase [>3 × ULN], increased serum aspartate aminotransferase [>3 × ULN: 2% to 3%])
Nervous system: Headache, myasthenia
Respiratory: Upper respiratory tract infection
Frequency not defined:
Endocrine & metabolic: Decreased serum triglycerides (females), hypercholesterolemia (total), increased LDL cholesterol
Gastrointestinal: Abdominal cramps, anorexia, biliary colic, bowel urgency, dyspepsia, epigastric discomfort, flatulence, heartburn, nausea, vomiting
Hematologic & oncologic: Decreased white blood cell count
Postmarketing:
Hepatic: Chronic active hepatitis, hepatotoxicity
Hypersensitivity: Hypersensitivity reaction
Chenodal: Known hepatocyte dysfunction or bile ductal abnormalities (eg, intrahepatic cholestasis, primary biliary cirrhosis, sclerosing cholangitis); gallbladder confirmed as nonvisualizing after two consecutive single doses of dye; radiopaque stones; gallstone complications or compelling reasons for gallbladder surgery (eg, unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, biliary gastrointestinal fistula); use in pregnancy or in patients who can become pregnant.
Ctexli: There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Diarrhea: Dose-related diarrhea commonly occurs (up to 40% of patients); may occur at any time, but is most common during treatment initiation. Diarrhea is usually mild and does not interfere with therapy; however, diarrhea may be severe and a temporary dosage reduction or discontinuation may be required. Antidiarrheal agents may be of benefit in some patients.
• Hepatotoxicity: Drug-induced liver toxicity may occur (dose-related); close monitoring of serum aminotransferase levels recommended during therapy. Aminotransferase elevations >3 times ULN have been reported. Biochemical and histologic chronic active hepatitis has been reported (rare case reports), although a causal relationship to chenodiol could not be determined. Cerebrotendinous xanthomatosis patients with preexisting liver disease or bile duct abnormalities may be at increased risk for hepatoxicity; patients who are poor sulfators of lithocholic acid have an increased risk of developing chenodiol-induced serum aminotransferase elevations.
Disease-related concerns:
• Colon cancer: Epidemiologic studies have suggested that bile acids may increase the risk of colon cancer. Evidence is weak and conflicting; however, a potential link between bile acids and colon cancer cannot be ruled out.
• Hepatic impairment: Avoid use in patients with preexisting hepatic impairment or elevated liver enzymes; use contraindicated in patients with known hepatocyte dysfunction or bile ductal abnormalities.
Other warnings/precautions:
• Gallstone recurrence: May occur within 5 years in approximately 50% of patients; serial cholecystograms or ultrasonograms are recommended to monitor for recurrence. Prophylactic doses have not been established and reduced doses cannot be recommended. Long-term consequences of repeated courses or chenodiol are not known.
Ctexli: FDA approved February 2025; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Ctexli tablets are indicated for the treatment of cerebrotendinous xanthomatosis in adults. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Chenodal: 250 mg
Ctexli: 250 mg
No
Tablets (Chenodal Oral)
250 mg (per each): $695.15
Tablets (Ctexli Oral)
250 mg (per each): $716.00
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Prescriptions are only dispensed by Dohmen Life Science Services Chenodal Total Care Program which may be contacted at 866-758-7068.
Oral: May be taken without regard to meals. Swallow tablets whole.
Oral: May be taken without regard to meals.
Gallstone dissolution (Chenodal): Dissolution of radiolucent cholesterol gallstones in select patients as an alternative to surgery.
Limitations of use: Will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.
Cerebrotendinous xanthomatosis (Ctexli): Treatment of cerebrotendinous xanthomatosis in adult patients.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aluminum Hydroxide: May decrease serum concentration of Chenodiol. Risk C: Monitor
Bile Acid Sequestrants: May decrease serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce the magnitude of this interaction. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants. Risk D: Consider Therapy Modification
Elobixibat: May decrease absorption of Chenodiol. Risk C: Monitor
Estrogen Derivatives: May decrease therapeutic effects of Chenodiol. Risk C: Monitor
Vitamin K Antagonists: Chenodiol may increase anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Use is contraindicated in women who may become pregnant.
Use is contraindicated in women who are pregnant. Adverse events were observed in some animal reproduction studies.
It is not known if chenodiol is excreted in breast milk. The manufacturer recommends that caution be exercised when administering chenodiol to breastfeeding women.
Cerebrotendinous xanthomatosis: Serum aminotransferase levels at baseline and yearly as indicated.
Other indications: Serum aminotransferase monthly for first 3 months, then every 3 months thereafter during therapy; serum cholesterol (every 6 months); oral cholecystograms and/or ultrasonograms (at 6- to 9-month intervals for response to therapy); dissolutions of stones should be confirmed 1 to 3 months later.
Chenodiol (chenodeoxycholic acid) is a naturally occurring human bile acid, normally constituting one-third of the total bile acid pool. In patients with cholesterol gallstones, chenodiol is believed to suppress hepatic synthesis of cholesterol and cholic acid, and inhibit biliary cholesterol secretion, which leads to increased production of cholesterol unsaturated bile thereby allowing for dissolution of gallstones. Patients with cerebrotendinous xanthomatosis are deficient in endogenous levels of chenodeoxycholic acid. Chenodiol increases chenodiol levels in the enterohepatic bile acid pool to restore the activation of farnesoid X receptor and downregulate CYP7A1 which may lead to suppression and reduction of atypical bile acids and bile alcohols, including cholestanol and 23S-pentol.
Absorption: Chenodal: Rapid, almost completely absorbed in proximal small intestine (Crosignani 1996).
Distribution: Vd: Chenodal: ~1,600 L (Crosignani 1996); Ctexli: 0.36 L/kg.
Protein binding: Ctexli: ~98%.
Metabolism: Converted hepatically to taurine and glycine conjugates and secreted in bile; extensive first-pass hepatic clearance; undergoes enterohepatic circulation; further metabolized in colon by bacteria to lithocholic acid; small portion of lithocholate is absorbed and converted to sulfolithocholyl conjugates in the liver
Half-life: Chenodal: ~45 hours (Crosignani 1996).
Time to peak: Ctexli: 3 hours (range: 0.5 to 8 hours).
Excretion: Chenodal: Feces (~80%, as lithocholate).
Clearance: Ctexli: 20 L/hour.
