Drug Detail:Chenodiol (Chenodiol (chenodeoxycholic acid) [ kee-noe-dye-ol ])
Drug Class: Gallstone solubilizing agents
Usual Adult Dose for Gallbladder Disease
Initial dose: 250 mg orally 2 times a day
Maintenance dose: 13 to 16 mg/kg/day in 2 divided doses
Duration of therapy: 24 months
Comments:
- After the first 2 weeks, the dose should be increased by 250 mg/day each week thereafter until the recommended or maximum tolerated dose is reached.
- Doses less than 10 mg/kg were usually ineffective and may be associated with an increased risk of cholecystectomy.
- Oral cholecystograms or ultrasonograms should be conducted at 6 to 9 months.
- Most patients who achieve complete dissolution will show at least partial dissolution at the first on-treatment test. Complete dissolution should be confirmed with oral cholecystogram or ultrasonogram after 1 to 3 months of continued treatment.
Use: Patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease/age
Renal Dose Adjustments
Data not available
Liver Dose Adjustments
Serum aminotransferase level monitoring: Monthly for the first 3 months, then every 3 months thereafter.
- Minor, usually transient elevations (1.5 to 3 times upper limit of normal [1.5 to 3 x ULN]) persisting longer than 3 to 6 months: Treatment should be discontinued and should not be resumed until levels return to normal.
- Some experts state that safety of allowing elevations to persist is unknown.
- Elevations over 3 x ULN: Treatment should be discontinued immediately. Elevations have recurred on rechallenge.
Dose Adjustments
Cholesterol levels: Treatment discontinuation should be considered in patients if cholesterol levels rise above acceptable age-adjusted limits.
Diarrhea occurring during treatment: Temporarily adjust the dose until symptoms abate, then continue treatment with the previous dose.
Lack of response: Treatment should be discontinued if there is no response by 18 months.
Precautions
US BOXED WARNINGS:
SPECIAL NOTE:
- Because of the potential hepatotoxicity of this drug, poor response rate in some subgroups of patients treated with this drug, and an increased rate of a need for cholecystectomy in other subgroups treated with this drug, this drug is not an appropriate treatment for many patients with gallstones.
- This drug 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.
Safety and efficacy have not been established in children.
Consult WARNINGS section for additional precautions.
Dialysis
Data not available
Other Comments
Administration advice:
- Doses may be taken without regard to food.
- Capsules should be taken with water at the same time each day.
- For patients who cannot swallow, some capsule formulations may be opened and mixed with an 8.4% sodium bicarbonate solution prior to administration.
Storage requirements:
- Prepared suspension formulations should be stored in a glass bottle, and may be stored for up to 7 days.
- Prepared suspensions should not be refrigerated or frozen.
Reconstitution/preparation techniques:
- Prepared suspensions: The manufacturer product information should be consulted.
General:
- This drug will not dissolve calcified/radiopaque or radiolucent bile pigment stones.
- Successful dissolution is greater in smaller and/or floatable stones. Emergent surgery may result from a delay due to unsuccessful treatment in patients with unfloatable stones.
- Some experts recommend that treatment should be limited to healthcare providers experienced in the management of cerebrotendinous xanthomatosis or inborn errors of primary bile acid synthesis.
Monitoring:
- Gastrointestinal: Cholecystogram, at least every 6 months
- Genitourinary: Urine bile alcohols, at least yearly
- Hepatic: Liver function tests
- Metabolic: Serum cholesterol, serum cholestenol at least every 6 months
Patient advice:
- Inform patients that this drug may cause (dizziness, blurred vision, somnolence, etc.), and they should avoid driving or operating machinery if these side effects occur.
- Counsel patients on the importance of periodic liver function tests, oral cholecystograms/ultrasonograms, and compliance with the dosage regimen.
- Instruct patients to immediately report signs/symptoms of gallstone complications.
- Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
