(kee noe DYE ole)
Gallstone dissolution: Dissolution of radiolucent cholesterol gallstones in selected patients as an alternative to surgery
Limitations of use: Will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.
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); use in pregnancy or in women who can become pregnant.
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.
Gallstone dissolution (monotherapy): Oral: 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 to 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): Oral: 5 to 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)
Cerebrotendinous xanthomatosis (off-label use): Oral: 750 mg/day in 3 divided doses for at least 1 year (Berginer 1984)
There are no dosage adjustments provided in the manufacturer 's labeling.
Preexisting hepatic impairment: There are no dosage adjustments provided in the manufacturer 's labeling; Avoid use in patients with preexisting hepatic impairment. Contraindicated for use in presence of known hepatocyte dysfunction or bile duct abnormalities.
Hepatotoxicity during treatment:
Aminotransferase level 1.5 to 3 times ULN persisting for >3 to 6 months: Temporarily withhold treatment; resume when aminotransferases levels return to normal
Aminotransferase level >3 times ULN: Discontinue treatment immediately
Store at 20 ‚ °C to 20 ‚ °C (68 ‚ °F to 77 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Chenodal: 250 mg
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
Vitamin K Antagonists (eg, warfarin): Chenodiol may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Serum aminotransferase levels (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
Frequency not always defined. *Incidence not specifically defined, but reported in the range of >10%.
Endocrine & metabolic: Increased LDL cholesterol, increased serum cholesterol (total)
Gastrointestinal: Diarrhea (30% to 40%; severe diarrhea that requires dose reduction: 10% to 15%), increased aminotransferases ( ≥30%; >3 x ULN: 2% to 3%), biliary colic,* abdominal cramps, abdominal pain, anorexia, constipation, dyspepsia, flatulence, heartburn, nausea, vomiting
Hematologic & oncologic: Leukopenia
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; prompt discontinuation of therapy recommended. Transaminase levels usually return to normal after chenodiol is withheld. Temporarily withhold therapy for transient transaminase elevations of 1.5 to 3 times ULN. Biochemical and histologic chronic active hepatitis has been reported (rare case reports), although a causal relationship to chenodiol could not be determined.
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.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Other warnings/precautions:
- Appropriate use: [US Boxed Warning]: Due to the hepatotoxicity potential, poor response rate in certain subgroups, and an increased rate of cholecystectomy necessary in other subgroups, chenodiol is not an appropriate treatment for many patients with gallstones. Use should be reserved to carefully selected patients; treatment must be accompanied with liver function monitoring. 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.
- 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 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.
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Use is contraindicated in women who are or can become pregnant. Adverse events were observed in some animal reproduction studies.
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.
Rapid, almost completely absorbed in proximal small intestine (Crosignani 1996)
Vd: ~1600 L (Crosignani 1996)
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
Feces (~80%, as lithocholate)
~45 hours (Crosignani 1996)
- 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, vomiting, abdominal cramps, abdominal pain, constipation, flatulence, heartburn, or lack of appetite. Have patient report immediately to prescriber signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes) or severe diarrhea (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.