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.

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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

Adults

PO 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 contraceptives

Because 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.

Warfarin

Because 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

Warnings

Chenodiol 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.


Monitor

Monitor 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.

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