Chenodiol
Pronunciation: KEE-noe-DYE-ol
Class: Gallstone solubilizing agent
Trade Names
Chenodal
- Tablets 250 mg
Pharmacology
Suppresses hepatic synthesis of cholesterol and cholic acid, contributing to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones.
Pharmacokinetics
Absorption
Well absorbed from the small intestine.
Distribution
The body pool of chenodiol resides mainly in the enterohepatic circulation.
Metabolism
Converted in the liver to taurine and glycine conjugates and secreted in the bile. At steady state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacteria to lithocholic acid.
Elimination
About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to a poorly absorbed sulfolithocholyl conjugate.
Indications and Usage
Dissolution of gallbladder stones in patients with radiolucent stones in well-opacifying gallbladders, in whom elective surgery would be undertaken except for the presence of increased surgical risk because of systemic disease or age.
Contraindications
Known hepatocyte dysfunction or bile ductal abnormalities such as intrahepatic cholestasis, primary biliary cirrhosis, or sclerosing cholangitis; gallbladder confirmed as nonvisualizing after 2 consecutive single doses of dye; radiopaque stones; gallstone complications or compelling reasons for gallbladder surgery including unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis, or biliary GI fistula; women who are or may become pregnant.
Dosage and Administration
AdultsPO 13 to 16 mg/kg/day in 2 divided doses, morning and night. Start with 250 mg twice daily for the first 2 weeks and increase by 250 mg/day each week thereafter until the recommended usual dose or max tolerated dose is reached.
General Advice
- If diarrhea occurs during dosage buildup or later in treatment, temporarily decrease the dosage until symptoms resolve.
- Discontinue treatment if no response is seen by 18 mo; safety of use beyond 24 mo is not established.
Storage/Stability
Store at 68° to 77°F.
Drug Interactions
Aluminum-based antacids (eg, aluminum-hydroxide), bile acid sequestrants (eg, cholestyramine, colestipol)Chenodiol absorption may be reduced, decreasing the pharmacologic effect. Coadminister with caution. Consider separating the administration times by as much as possible. If an interaction is still suspected, consider discontinuing one of the drugs.
Clofibrate, estrogens, hormonal contraceptivesBecause these agents increase biliary cholesterol secretion and the incidence of cholesterol gallstones, chenodiol effectiveness may be counteracted. Coadminister with caution. If an interaction is suspected, consider discontinuing one of the drugs.
WarfarinBecause chenodiol is hepatotoxic, warfarin pharmacodynamics may be affected, resulting in PT prolongation and hemorrhage. Carefully monitor anticoagulant parameters. Adjust the warfarin dose as needed or discontinue chenodiol therapy.
Laboratory Test Interactions
None well documented.
Adverse Reactions
GI
Dose-related diarrhea (30% to 40%).
Hepatic
Evidence of intrahepatic cholestasis (89%).
Lab Tests
Increased ALT (at least 30%).
Precautions
WarningsChenodiol is not an appropriate treatment for many patients with gallstones because of the potential for hepatotoxicity, poor response rates in some subgroups, and an increased rate of need for cholecystectomy in some subgroups. Reserve for carefully selected patients and systematically monitor for liver function alterations. |
MonitorMonitor serum aminotransferase levels monthly for the first 3 mo and every 3 mo thereafter during therapy. Monitor serum cholesterol at 6-mo intervals. Oral cholecystograms or ultrasonograms are recommended at 6- to 9-mo intervals to monitor response; repeat test to confirm complete dissolutions after 1 to 3 mo of continued chenodiol therapy. |
Pregnancy
Category X .
Lactation
Undetermined.
Children
Safety and efficacy not established.
Hepatic Function
Safe use depends upon selection of patients without preexisting liver disease.
Cholecystectomy
Increased rate of need for cholecystectomy seen in patients on lower dosages of chenodiol.
Colon cancer
Studies suggest bile acids might be involved in pathogenesis of human colon cancer; however, direct evidence is lacking.
Gallstone recurrence
May recur within 5 yr in 50% of patients. Indications for and safety of retreatment are not well defined.
Hepatic effects
Aminotransferase elevations may occur. If minor, transient elevations (1.5 to 3 times the ULN) persists for more than 3 to 6 mo, discontinue chenodiol and resume only after the aminotransferase level returns to normal. Elevations over 3 times the ULN require immediate discontinuation of therapy and usually reoccur on challenge.
Lipid elevations
May occur; primarily elevations in total cholesterol and LDL.
Overdosage
Symptoms
None well documented.
Patient Information
- Inform patients of the importance of periodic visits for liver function tests and tests for monitoring stone dissolution.
- Inform patients of the symptoms of gallstone complications and advise them to report such symptoms immediately to their health care provider.
- Inform patients that temporary dosage reduction may be necessary if episodes of diarrhea occur. Use of an antidiarrheal has been helpful in some patients.
Copyright © 2009 Wolters Kluwer Health.
