Chenodiol (chenodeoxycholic acid) is a naturally occurring human bile acid.1, 24
Chenodiol (Chenodal® only) is used for dissolution of gallstones in patients with radiolucent stones in well-opacifying gallbladders who are not candidates for elective surgery because of systemic disease or advanced age.1 Chenodiol is designated an orphan drug by FDA for this indication.3
Safety and efficacy of chenodiol were evaluated in a double-blind, randomized, placebo-controlled study (National Cooperative Gallstone Study [NCGS]) that included 915 patients with radiolucent gallstones present in functioning gallbladders.1, 20 Patients were randomized to receive chenodiol 375 mg daily, chenodiol 750 mg daily, or placebo.1, 5, 20 Complete dissolution of gallstones occurred in 0.8, 5.2, or 13.5% of patients receiving placebo, 375 mg of chenodiol, or 750 mg of chenodiol, respectively, over 24 months of treatment.1, 5, 20 In a subgroup having small (<15 mm in diameter) radiolucent stones receiving 750 mg of chenodiol daily, complete dissolution was observed in about 20% of patients.1, 20 Additionally, patients with a history of biliary pain prior to treatment had higher cholecystectomy rates with low-dosage chenodiol (375 mg daily) compared to either placebo or high-dosage chenodiol (750 mg daily).1, 20
In uncontrolled trials, complete dissolution rates of 28-38% have been observed in patients receiving chenodiol at dosages higher than those used in NCGS (i.e., 13-16 mg/kg daily) for up to 24 months.1 In these trials, rates of complete dissolution for small radiolucent stones ranged from 42-60%.1 Even higher dissolution rates have been observed in patients with small floatable stones.1 In a prospective trial, 31% of enrolled surgical-risk patients receiving chenodiol 15 mg/kg daily for more than 6 months achieved complete dissolution.1
Some obese patients and occasional patients with normal weight fail, for unknown reasons, to achieve bile desaturation even with dosages of chenodiol up to 19 mg/kg daily.1 The association of cholecystectomy with low-dosage chenodiol, although not clearly a causal one, suggests that patients unable to take higher doses of chenodiol may be at greater risk of cholecystectomy.1
A major finding in clinical trials was a difference between floatable and nonfloatable stones, with respect to both natural history and response to chenodiol.1 Over the 2-year course of NCGS, placebo-treated patients with floatable stones had significantly higher rates of biliary pain and cholecystectomy than patients with nonfloatable stones (47% versus 27% and 19% versus 4%, respectively).1 Administration of chenodiol (750 mg daily) compared with placebo was associated with substantial reduction in both biliary pain and cholecystectomy rates in the group with floatable stones (27 versus 47% and 1.5 versus 19%, respectively).1 In an uncontrolled clinical trial using chenodiol dosages of 15 mg/kg daily, 70% of patients with small (<15 mm) floatable stones had complete confirmed dissolution.1 In NCGS patients with nonfloatable stones, chenodiol produced no reduction in biliary pain and tended to increase the cholecystectomy rate (8 versus 4%).1 This finding was more pronounced with dosages of chenodiol <10 mg/kg daily.1 The subgroup of patients with nonfloatable stones and a history of biliary pain had the highest rates of cholecystectomy and serum aminotransferase elevations during chenodiol treatment.1 Dose-related aminotransferase elevations and diarrhea have occurred with equal frequency in patients with floatable or nonfloatable stones, except for the subgroup with pretreatment biliary pain.1 In the uncontrolled clinical trial, 27% of the patients with nonfloatable stones had complete confirmed dissolution, including 35% with small and 11% with large, nonfloatable stones.1
In a double-blind controlled study, patients with radiolucent gallstones in a functioning gallbladder were randomized to receive ursodeoxycholic acid 800 mg, chenodiol 750 mg, ursodeoxycholic acid 400 mg, or chenodiol 375 mg daily, or placebo.4 Ursodeoxycholic acid was significantly more effective than chenodiol in dissolving gallstones after 12 months of treatment.4 Although there continued to be better dissolution during ursodeoxycholic acid treatment (complete dissolution in 30% and partial dissolution in 30%) than during chenodiol treatment (complete dissolution in 7% and partial dissolution in 40%) at 24 months, the difference between the treatment groups was no longer statistically significant.4 The incidence of floating stones was significantly higher in patients who had stone dissolution than in those who did not.4 Floating stones failed to dissolve in 3 patients receiving chenodiol (750 mg daily [2 patients] or 375 mg daily [1 patient]) versus none of those receiving ursodeoxycholic acid.4 Gallstone dissolution with ursodeoxycholic acid occurred despite a rise in biliary cholesterol saturation, which was consistent with a nonmicellar mechanism of cholelitholysis.4 ALT concentrations increased by more than threefold in 2 patients receiving chenodiol (375 or 750 mg daily) and none of those receiving ursodeoxycholic acid; the enzyme levels returned to normal following discontinuance of chenodiol and remained normal during 13 or 8 months, respectively, of therapy with ursodeoxycholic acid 800 mg daily.4 The study results indicate that ursodeoxycholic acid dissolves gallstones faster and with fewer adverse effects than chenodiol.4, 8, 9 The results of the study also suggest that ursodeoxycholic acid is cholelitholytic at a lower dose than is chenodiol.4
Results of a randomized multicenter study indicate that there is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodiol compared with ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.10
Gallstones are a common occurrence among individuals in the US, although up to 70% are asymptomatic.21 The most common type of gallstone found among patients in the US (about 75%) is comprised primarily of cholesterol.21, 22 Treatment for gallstones is dependent on whether the patient is asymptomatic or symptomatic.22 For asymptomatic patients, treatment is based on the risk of symptom development or complications.22 Standard therapy is expectant management; however, for some patients, prophylactic cholecystectomy may be considered.21, 22 For symptomatic patients who are surgical candidates, laparoscopic cholecystectomy is recommended; for patients who are not surgical candidates, oral dissolution therapy (e.g., ursodeoxycholic acid or chenodiol) or extracorporeal shock wave therapy may be considered.22, 23
Cerebrotendinous Xanthomatosis (CTX)
Chenodiol (Ctexli™ only) is used for the treatment of CTX in adults.24 Chenodiol is designated an orphan drug by FDA for this indication.3
The safety and efficacy of chenodiol for treatment of CTX were evaluated in the RESTORE trial, a 24-week, randomized, double-blind study enrolling 14 adult patients.24, 25 Patients were given chenodiol 250 mg three times daily for two 8-week periods (an 8-week run-in and an 8-week open label period) in between two 4-week, double-blind, withdrawal periods where patients received either chenodiol or placebo.24, 25 Thirteen patients were randomized; 62% were male, 62% were white, and 15% were Asian, with a baseline median age of 42 years.24 Change from baseline in urinary bile alcohol 5ß-cholestane-3α, 7α, 12α, 23S, 25-pentol biomarker and change in plasma cholesterol were evaluated for each double-blind period.24, 25 Mean change in plasma cholesterol from baseline was -2.3 mcg/mL with chenodiol and +6.2 mcg/mL for placebo.24 For urine 23S-pentol, mean change with chenodiol was +185 ng/mL and +29506 ng/mL with placebo.24
Cerebrotendinous xanthomatosis is a rare, genetic lipid storage disorder that manifests as a deficiency in bile acids and an accumulation of cholesterol metabolites in various tissues (e.g., tendons and brain), resulting in progressive neurologic dysfunction.26, 27 Early diagnosis and treatment is critical in preventing complications of CTX.26 Standard of care for CTX is chenodiol given as 250 mg three times daily; weight-based dosing is used for children†.26, 27 The goal of treatment is to stabilize or improve neurologic symptoms of CTX.27
Chenodiol is administered orally 2-3 times daily.1, 24 Swallow tablets whole.24 For Ctexli™ tablets, if a dose is missed, advise the patient to skip the missed dose and to resume taking the prescribed dose at the next scheduled time.24 Doubling the dose is not recommended.24
Store tablets in a tight container at 20-25°C.1, 24
For Ctexli™ tablets, excursions permitted between 15-30°C.24
The recommended dosage of Chenodal® for dissolution of gallstones in adults with radiolucent stones in well-opacifying gallbladders is 13-16 mg/kg daily, given in 2 divided doses (morning and evening).1 The recommended initial dosage is 250 mg twice daily for the first 2 weeks.1 Increase dosage by 250 mg daily each week thereafter, until the recommended or maximum tolerated dosage is reached.1 Discontinue the drug if there is no response by 18 months.1
Dosages less than 10 mg/kg daily usually are ineffective and may be associated with increased risk of cholecystectomy; therefore, such dosages are not recommended.1 More information on recommended adult dosages is presented in Table 1.
Body Weight (kg) | Recommended No. Tablets Daily | Daily Dosage Range (mg/kg) |
|---|---|---|
45-58 | 3 | 13-17 |
59-75 | 4 | 13-17 |
76-90 | 5 | 14-18 |
91-107 | 6 | 14-18 |
108-125 | 7 | 14-18 |
Cerebrotendinous Xanthomatosis
The recommended dosage of Ctexli™ for treatment of cerebrotendinous xanthomatosis in adults is 250 mg orally three times daily with or without food.24
Dosage Modifications for Toxicity
In patients with gallstones, if diarrhea occurs during dosage titration or later during treatment, temporarily adjust dosage until symptoms abate, after which the previous dosage usually is tolerated.1
In patients with gallstones, if aminotransferase levels are elevated >3 times the upper limit of normal (ULN), discontinue chenodiol treatment.1
In patients with cerebrotendinous xanthomatosis, if liver transaminase (ALT, AST) levels are elevated >3 times the ULN or total bilirubin level is >2 times ULN, interrupt treatment until the levels have returned to baseline values.24 Monitor liver transaminase and total bilirubin levels yearly and as clinically indicated.24
For patients receiving treatment for gallstone dissolution, the use of Chenodal® in hepatic impairment is contraindicated.1 The manufacturer of Ctexli™ provides no specific dosage recommendations for patients with hepatic impairment.24
The manufacturer provides no specific dosage recommendations for patients with renal impairment.1, 24
The manufacturer provides no specific dosage recommendations for geriatric patients.1, 24
Chenodal®
Hepatotoxicity has been reported in association with chenodiol therapy.1, 2, 4, 24 In the National Cooperative Gallstone Study (NCGS), significant hepatotoxicity (defined as either a major abnormality identified in a liver biopsy specimen by light microscopy or a major elevation in serum aminotransferase levels) occurred in 3% of patients receiving chenodiol dosages of 750 mg daily while such hepatotoxicity occurred in only 0.4% of patients receiving chenodiol dosages of 375 mg daily or placebo.2 In 2-3% of patients receiving the drug, serum aminotransferase (mainly ALT) elevations exceeded 3 times the upper limit of normal (ULN), recurred on rechallenge with the drug, and required discontinuance of chenodiol treatment.1 Hepatic enzyme concentrations returned to normal following withdrawal of the drug.1 Although clinical and biopsy studies have not shown fulminant lesions, the possibility remains that an occasional patient may develop serious hepatic disease.1
Dose-related serum aminotransferase (mainly ALT) elevations, usually not accompanied by elevations of alkaline phosphatase or bilirubin, occurred in 30% or more of patients receiving recommended doses of chenodiol.1 In most cases, these elevations were minor (1.5-3 times ULN) and transient, returning to the normal range within 6 months despite continued administration of the drug.1
Morphologic studies of liver biopsy specimens obtained before and after 9 and 24 months of treatment with chenodiol have shown that 63% of patients had evidence of intrahepatic cholestasis prior to chenodiol treatment.1 Almost all patients had pretreatment electron microscopic abnormalities.1 By the ninth month of treatment, reexamination of 66% of patients showed an 89% incidence of signs of intrahepatic cholestasis.1
In patients with gallstones, if aminotransferase levels are elevated >3 times ULN, discontinue chenodiol treatment.1
Ctexli™
In a trial evaluating Ctexli™ efficacy and safety, one patient (7%) had increased ALT levels >3 times ULN, which led to treatment interruption.24 Patients with pre-existing liver disease or bile duct abnormalities may be at higher risk for hepatotoxicity during treatment.24 Published reports suggest patients who are poor sulfators of lithocholic acid are more likely to develop chenodiol-induced serum aminotransferase elevations.24
Obtain baseline liver transaminase (ALT, AST) and total bilirubin levels in all patients prior to treatment initiation.24 If liver transaminase levels are elevated >3 times ULN or total bilirubin level is >2 times ULN, interrupt treatment until the levels have returned to baseline values.24 Monitor liver transaminase and total bilirubin levels yearly and as clinically indicated.24 For persistent or recurrent liver test abnormalities, consider discontinuing treatment.24
Inform patients of the symptoms of hepatotoxicity (e.g., abdominal pain, bruising, dark-colored urine, fatigue, bleeding, jaundice, nausea, pruritus).24 If clinical signs and symptoms consistent with hepatotoxicity occur, have the patient discontinue therapy immediately.24
Chenodal®
Epidemiologic studies suggest that bile acids might contribute to human colon cancer, but direct evidence is lacking.1 Bile acids, including chenodiol and lithocholic acid, have no carcinogenic potential in animal models, but have been shown to increase the number of tumors when administered with certain carcinogens.1 The possibility that chenodiol therapy might contribute to colon cancer in otherwise susceptible individuals cannot be ruled out.1
Chenodal® may cause fetal harm when administered during pregnancy based on animal studies.1 Serious hepatic, renal, and adrenal lesions occurred in fetuses of female Rhesus monkeys given 60 to 90 mg/kg per day (4 to 6 times the maximum recommended human dose, MRHD) from day 21 to day 45 of pregnancy.1, 24 Hepatic lesions also occurred in neonatal baboons whose mothers had received 18 to 38 mg/kg, all during pregnancy.1, 24
Fetal malformations were not observed.1 Neither fetal liver damage nor fetal abnormalities occurred in reproduction studies in rats and hamsters.1
Chenodal® is contraindicated in women who are or may become pregnant.1 If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, inform the patient of the potential hazard to the fetus.1
Ctexli™ (used for cerebrotendinous xanthomatosis) does not have a contraindication for use in pregnancy.24 According to the manufacturer, the safety findings in animal studies have not been observed with human use.24
It is not known whether chenodiol is distributed into human or animal milk or its effect on the breast-fed infant or on milk production.1, 24 Use the drug with caution in nursing women, taking into consideration the mother's clinical need for the drug and potential adverse effects on the breast-fed infant from the medication or the underlying maternal condition.1, 24
Safety and efficacy of chenodiol in pediatric patients have not been established.1, 24
Evaluation of Ctexli™ in patients with cerebrotendinous xanthomatosis did not include patients ≥65 years of age.24
Chenodiol undergoes first-pass hepatic clearance and is hepatically metabolized.1, 24 Its use for gallstone dissolution in patients with pre-existing hepatic impairment is contraindicated.1 Information on appropriate use for cerebrotendinous xanthomatosis in patients with pre-existing hepatic impairment is not available.24
The manufacturer does not provide information on use in patients with renal impairment.1, 24
Chenodal®: Serum aminotransferase elevations, diarrhea (usually mild, translucent, well tolerated), increased serum total cholesterol and low-density lipoprotein (LDL)-cholesterol, and decreased leukocyte count (not below 3000/mm3) have been reported.1
Ctexli™: The most common adverse reactions (incidence >14%) are diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory infection.24
Chenodiol and its glyco- and tauro-conjugates are not expected to inhibit cytochrome P450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4, or induce CYP 1A2 or 2B6 at the recommended dose of chenodiol of 250 mg three times daily.24 Chenodiol and its tauro-conjugate may upregulate CYP3A4 mRNA.24 The clinical significance of this in vitro upregulation is unknown.24
The glyco- and tauro-conjugates of chenodiol are high affinity substrates for bile salt export pump (BSEP), and studies suggest that chenodiol may inhibit organic anion transporting polypeptide (OATP)1B1 and 1B3 at the in vitro recommended dose of 250 mg three times daily (clinical significance unknown).24 Chenodiol and its glyco- and tauro-conjugates are not predicted to inhibit P-glycoprotein, breast cancer resistance protein (BCRP), OATP2B1, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)1, OCT2, multidrug and toxin compound extrusion (MATE)1, or MATE2-K.24
Concomitant administration of aluminum-containing antacids may result in decreased absorption of chenodiol.1, 24 Avoid concomitant use.24
Cholestyramine and colestipol decrease absorption of chenodiol.1, 24 Avoid concomitant use.24
Coumarin-derivative Anticoagulants
Because of its hepatotoxic effects, chenodiol can affect the pharmacodynamics of coumarin derivatives resulting in unexpected prolongation of the prothrombin time and hemorrhage.1, 24 Carefully monitor patients receiving chenodiol concomitantly with a coumarin derivative, and adjust dosage of the coumarin derivative as required.1, 24 If needed, discontinue chenodiol.1
Possible reduced efficacy of chenodiol because of increased biliary cholesterol secretion caused by estrogens.1
Possible reduced efficacy of chenodiol because of increased biliary cholesterol secretion caused by oral contraceptives.1
Chenodal®
At therapeutic doses, chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid, in an expanded bile acid pool.1 These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gallbladder visualized by oral cholecystography.1 Chenodiol has no effect on radiopaque (calcified) gallstones or on radiolucent bile pigment stones.1
Ctexli™
Endogenous chenodiol (chenodeoxycholic acid) is a primary bile acid, synthesized from cholesterol in the liver.24 In cerebrotendinous xanthomatosis (CTX), the major bile acid synthesis pathways are disrupted due to partial or total deficiency in sterol 27-hydroxylase encoded by the CYP27A1 gene.24
Ctexli™ may act to replace deficient levels of the endogenous bile acid chenodeoxycholic acid in patients with CTX.24 Increased chenodiol levels in the enterohepatic bile acid pool restore the activation of farnesoid X receptor (FXR) and downregulate CYP7A1 leading to suppression and reduction of atypical bile acids and bile alcohols including cholestanol and 23S-pentol.24
In the trial of patients treated for CTX, plasma cholestanol and urine 23S-pentol concentrations were elevated.24 Treatment resulted in reductions of plasma cholestanol and urine 23S-pentol concentrations in the 8-week run-in, open label treatment period.24 Continued treatment for 4 weeks in the double-blind treatment period resulted in the maintenance of low levels of urine 23S-pentol and additional reductions of plasma cholestanol.24
Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted into the bile along with other endogenous bile acids in the enterohepatic circulation.1, 24 Due to first-pass hepatic clearance, the body pool of chenodiol resides mainly in the enterohepatic circulation.1, 24 The plasma protein binding of chenodiol is approximately 98%.24 Chenodiol that escapes to the colon is converted by bacterial action to lithocholic acid.1, 24 Humans have the capacity to form sulfate conjugates of lithocholic acid.1, 24 About 80% of the lithocholate is excreted in the feces and the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates.1, 24
Conjugated chenodiol is either reabsorbed in the terminal ileum, deconjugated before excretion, or decomposed by bacteria to lithocholic acid.1, 24
In patients with CTX, the median time to reach maximum concentration of Ctexli™ following oral administration was 3 (0.5 to 8) hours.24
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Ph=armacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Ctexli™ is obtained through designated specialty pharmacies. Contact the manufacturer or consult the Ctexli™ website ([Web]) for specific availability information.28
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 250 mg | Retrophin, Inc. | |
250 mg | Ctexli™ |
1. Retrophin, Inc. Chenodal® (chenodiol) tablets prescribing information. San Diego, CA; 2015 Jun.
2. Fisher RL, Hofmann AF, Converse JL et al. The lack of relationship between hepatotoxicity and lithocholic-acid sulfation in biliary bile acids during chenodiol therapy in the National Cooperative Gallstone Study. Hepatology . 1991; 14:454-63. [PubMed 1874490]
3. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2025 May 27. [Web]
4. Fromm H, Roat JW, Gonzalez V et al. Comparative efficacy and side effects of ursodeoxycholic and chenodeoxycholic acids in dissolving gallstones. A double-blind controlled study. Gastroenterology . 1983 Dec; 85:1257-64.
5. Grundy SM, Lan SP, Lachin J. The effects of chenodiol on biliary lipids and their association with gallstone dissolution in the National Cooperative Gallstone Study (NCGS). J Clin Invest . 1984; 73:1156-66. [PubMed 6368591]
8. Roda E, Bazzoli F, Morselli Labate AM et al. Ursodeoxycholic acid vs. chenodeoxycholic acid as cholesterol gallstone-dissolving agents: a comparative randomized study. Hepatology . 1982; 2:804-10. [PubMed 7141392]
9. Konikoff FM. Gallstones - approach to medical management. Med Gen Med . 2003; 5:8.
10. Petroni ML, Jazrawi RP, Pazzi P et al. Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group. Aliment Pharmacol Ther . 2001; 15:123-8. [PubMed 11136285]
20. Schoenfield LJ, Lachin JM, Baum RA, et al. Chenodiol (chenodeoxycholic acid) for dissolution of gallstones: the National Cooperative Gallstone Study. Ann Intern Med. 1981;95(3):257-282.
21. Lam R, Zakko A, Petrov J, et al. Gallbladder disorders: a comprehensive review. Dis Month. 2021;67(7):101130.
22. Ibrahim M, S Sarvepalli S, Morris-Stiff G, et al. Gallstones: watch and wait, or intervene. Cleve Clin J Med. 2018;85(4):323-331.
23. Abraham S, Rivero H, Erlikh I, et al. Surgical and nonsurgical management of gallstones. Am Fam Physician. 2014;89(10): 795-802.
24. Mirum Pharmaceuticals, Inc. CTEXLI (chenodiol) tablets prescribing information. Foster City, CA; 2025 Feb.
25. DeBarber A, Kisanuki Y, Nobrega P, et al. Efficacy, safety and tolerability of chenodeoxycholic acid in adult patients with cerebrotendinous xanthomatosis (RESTORE): a randomized, placebo-controlled phase 3 study. GIM Open. 2024; 2(Suppl 1): P142 [abstract]
26. DeBarber A, Duell PB. Update on cerebrotendinoius xanthomatosis. Curr Opin Lipidol. 2021; 32(2):123-131.
27. Nobrega P, Bernardes A, Ribeiro R, et al. Cerebrotendinous xanthomatosis: a practice review of pathophysiology, diagnosis, and treatment. Front Neurol. 2022;13:1049850
28. Mirum Pharmaceuticals. Mirum Access Plus. From Ctexli Website. Accessed May 19, 2025.