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Chenodiol

Pronunciation

(kee noe DYE ole)

Index Terms

  • CDCA
  • Chenodeoxycholic Acid

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Chenodal: 250 mg

Brand Names: U.S.

  • Chenodal

Pharmacologic Category

  • Bile Acid

Pharmacology

Chenodiol (chenodeoxycholic acid) is a naturally occurring human bile acid, normally constituting one-third of the total bile acid pool. Synthesis of chenodiol is regulated by the relative composition and flux of cholesterol and bile acids through the hepatocyte by a negative feedback effect on the rate-limiting enzymes for synthesis of cholesterol (HMG-CoA reductase) and bile acids (cholesterol 7 alpha-hydroxyl). 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.

Absorption

Rapid, almost completely absorbed in proximal small intestine (Crosignani 1996)

Distribution

Vd: 1600 L (Crosignani 1996)

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

Excretion

Feces (80%, as lithocholate)

Half-Life Elimination

45 hours (Crosignani 1996)

Use: Labeled Indications

Oral dissolution of radiolucent cholesterol gallstones in selected patients as an alternative to surgery

Use: Unlabeled

Cerebrotendinous xanthomatosis (CTX)

Contraindications

Presence of known hepatocyte dysfunction or bile ductal abnormalities (eg, intrahepatic cholestasis, primary biliary cirrhosis, sclerosing cholangitis); use in a patient with a 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); pregnancy

Dosage

Oral:

Cerebrotendinous xanthomatosis (off-label use): Adults: 750 mg daily in 3 divided doses (Beringer, 1984)

Gallstone dissolution (monotherapy): Adults: Initial: 250 mg twice daily for the first 2 weeks and increasing by 250 mg daily each week thereafter until the recommended or maximum tolerated dose is achieved; maintenance: 13-16 mg/kg/day in 2 divided doses. Note: Dosages <10 mg/kg are usually ineffective and may increase the risk of cholecystectomy.

Gallstone dissolution (combination therapy; off-label dose): Adults: 5-7.5 mg/kg/day once daily at bedtime, in combination with ursodeoxycholic acid, with or without adjuvant lithotripsy (Jazrawi, 1992; Pereira, 1997; Petroni, 2001)

Dosage adjustment in renal impairment: No dosage adjustment provided in manufacturer’s labeling.

Dosage adjustment in hepatic impairment: Use extreme caution; contraindicated for use in presence of known hepatocyte dysfunction or bile duct abnormalities

Storage

Store at 20°C to 20°C (68°F to 77°F).

Drug Interactions

Aluminum Hydroxide: May decrease the serum concentration of Chenodiol. Management: Consider administration of chenodiol 2 hours before or 6 hours after aluminum-containing antacid products to prevent adsorption in the gastrointestinal tract. Consider therapy modification

Bile Acid Sequestrants: May decrease the serum concentration of Chenodiol. Management: Administration of chenodiol 5 hours or more after bile acid sequestrants may reduce chenodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of chenodiol in patients receiving bile acid sequestrants. Consider therapy modification

Estrogen Derivatives: May diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any estrogen derivative. Monitor therapy

Fibric Acid Derivatives: May diminish the therapeutic effect of Chenodiol. Management: Monitor clinical response to chenodiol closely when used together with any fibric acid derivative. Monitor therapy

Adverse Reactions

>10%:

Gastrointestinal: Diarrhea (30% to 40%; severe diarrhea requiring dose reduction: 10% to 15%), biliary pain

Hepatic: Aminotransferase increased (≥30%; >3 times ULN: 2% to 3%)

Frequency not defined:

Endocrine & metabolic: LDL cholesterol increased, total cholesterol increased

Gastrointestinal: Abdominal cramps, abdominal pain, anorexia, constipation, dyspepsia, flatulence, heartburn, nausea, vomiting

Hematologic: Leukopenia

Warnings/Precautions

Concerns related to adverse effects:

• Diarrhea: Dose-related diarrhea commonly occurs (up to 40% of patients). 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.

• 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; prompt discontinuation of therapy recommended.

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 disease: Avoid or use with extreme caution in patients with hepatic impairment or elevated liver enzymes; use contraindicated in patients with known hepatocyte dysfunction or bile ductal abnormalities.

Other warnings/precautions:

• Appropriate use: Careful selection of appropriate patients is necessary prior to therapy; studies have shown dissolution rates are higher in patients with small (<15 mm in diameter), radiolucent, and/or floatable stones. Radiopaque (calcified or partially calcified) stones and bile pigment stones do not respond to bile acid dissolution therapy.

• Length of therapy: Response to therapy should be monitored with oral cholecystograms or ultrasonograms. Complete dissolution should be confirmed by one repeat test 1-3 months after continued therapy. If partial dissolution is not observed by 9-12 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.

Monitoring Parameters

Oral cholecystograms and/or ultrasonograms (6-9 month intervals for response to therapy); dissolutions of stones should be confirmed 1-3 months later; serum aminotransferase levels (monthly for first 3 months, then every 3 months during therapy); serum cholesterol (every 6 months)

Pregnancy Risk Factor

X

Pregnancy Considerations

Hepatic, renal, and adrenal lesions were observed in some animal reproduction studies. Use during pregnancy is contraindicated.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, dyspepsia, constipation, flatulence, pyrosis, or lack of appetite. Have patient report immediately to prescriber signs of hepatic impairment, significant diarrhea, or pharyngitis (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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