cholic acid

Adult Dosing

Bile acid synthesis disorders due to SEDs and peroxisomal disorders including Zellweger spectrum disorders

10-15 mg/kg PO qd or divided bid with food
In patients with concomitant familial hypertriglyceridemia : 11-17 mg/kg PO qd or divided bid with food

Note:

Refer package insert for number of capsules that should be administered daily to approximate a 10 mg/kg/day and 15 mg/kg/day dosage using the available 50 mg and 250 mg capsules alone or in combination
Take cholic acid at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin or aluminum-based antacid
Administer the lowest dose that effectively maintains liver function
The safety and effectiveness of cholic acid on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established

Monitoring

Monitor serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma glutamyltransferase (GGT), alkaline phosphatase (ALP), bilirubin, and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the subsequent three years and annually thereafter
More frequent monitoring is advised during periods of rapid growth, concomitant disease, and pregnancy
Discontinue therapy if liver function does not improve within 3 months of treatment initiation or if complete biliary obstruction develops
Discontinue therapy if clinical or laboratory indicators persistently suggest worsening liver function or cholestasis

Pediatric Dosing

Bile acid synthesis disorders due to SEDs and peroxisomal disorders including Zellweger spectrum disorders

<3 weeks: Safety and efficacy have not been established
3 weeks or older: 10-15 mg/kg PO qd or divided bid with food
In patients with concomitant familial hypertriglyceridemia : 11-17 mg/kg PO qd or divided bid with food

Note:

Refer package insert for number of capsules that should be administered daily to approximate a 10 mg/kg/day and 15 mg/kg/day dosage using the available 50 mg and 250 mg capsules alone or in combination
Take cholic acid at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin or aluminum-based antacid
Administer the lowest dose that effectively maintains liver function
The safety and effectiveness of cholic acid on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established

Monitoring

Monitor serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma glutamyltransferase (GGT), alkaline phosphatase (ALP), bilirubin and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the subsequent three years and annually thereafter
More frequent monitoring is advised during periods of rapid growth, concomitant disease, and pregnancy
Discontinue therapy if liver function does not improve within 3 months of treatment initiation or if complete biliary obstruction develops
Discontinue therapy if clinical or laboratory indicators persistently suggest worsening liver function or cholestasis

[Outline]

Indications ⬆ ⬇

Treatment of bile acid synthesis disorders due to single-enzyme defects (SEDs)
Adjunctive treatment of peroxisomal disorders (PDs), including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption

Note:

The safety and effectiveness of cholic acid on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established

Contraindications ⬆ ⬇

Black Box Warnings ⬆ ⬇

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Hepatic Dose Adjustment

Hepatic impairment: Discontinue treatment if liver function does not improve within 3 months of treatment initiation or at any time if clinical and laboratory indicators suggest worsening liver function or cholestasis

Warnings/Precautions ⬆ ⬇

Monitor liver function and discontinue therapy in case of exacerbation of liver impairment
Discontinue therapy if clinical or laboratory indicators are suggestive of worsening liver function or cholestasis
Concurrent elevations of serum GGT and ALT may indicate overdose; continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline
Discontinue treatment if liver function does not improve within 3 months of treatment initiation or if complete biliary obstruction develops

Supplemental Patient Information

Advise patients that they will need to undergo laboratory testing periodically while on treatment to assess liver function
Advise patients that cholic acid treatment may worsen liver impairment and that they should immediately report any symptoms associated with liver impairment to their health care provider

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy category: Not rated

Inform patients about the pregnancy surveillance program that monitors pregnancy outcomes in women exposed to cholic acid during pregnancy

Breastfeeding: Safety Unknown. Manufacturer advises caution.

Adverse Reactions ⬆ ⬇

Clinical Pharmacology ⬆ ⬇

Bile acid replacements; exact mechanism of action has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of FXR (a nuclear receptor called farnesoid X receptor) which regulates enzymes and transporters involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions
Metabolism: Metabolized in liver; CYP450: none
Excretion: Excreted in feces
Half-life: Unknown

Brands and Availability ⬆ ⬇