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Cholic Acid

Class: GI Drugs, Miscellaneous
Chemical Name: (4R) - 4 - [(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R) - 3,7,12 - trihydroxy - 10,13 - dimethyl - 2,3,4,5,6,7,8,9,11,12,14,15,16,17 - tetradecahydro - 1H - cyclopenta[a]phenanthren - 17 - yl]pentanoic acid
Molecular Formula: C24H40O5
CAS Number: 81-25-4
Brands: Cholbam

Introduction

Cholic acid is a primary bile acid.

Uses for Cholic Acid

Cholic acid has the following uses:

Cholic acid is a bile acid indicated for the treatment of bile acid synthesis disorders due to single enzyme defects (SEDs).1

Cholic acid also is indicated for 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. 1

Cholic acid has the following limitation of use:

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.1

Cholic Acid Dosage and Administration

General

Cholic acid is available in the following dosage form(s) and strength(s):

Capsules: 50 mg, 250 mg.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • The recommended dosage is 10 to 15 mg/kg daily, given either once daily or in two divided doses, in pediatric patients and adults. See prescribing information for weight-based dosing tables.1

  • The recommended dosage in patients with concomitant familial hypertriglyceridemia is 11 to 17 mg/kg daily, given either once daily or in two divided doses, and is adjusted based on clinical response.1

  • Monitor AST, ALT, GGT, alkaline phosphatase, bilirubin, and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the next three years, and annually thereafter. Administer the lowest dose that effectively maintains liver function.1

  • Discontinue cholic acid if liver function does not improve within 3 months of starting treatment, if complete biliary obstruction develops, or if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis; continue to monitor liver function and consider restarting at a lower dose when parameters return to baseline.1

  • Administration Instructions
  • Take with food.1

  • Do not crush or chew the capsules. For patients unable to swallow the capsules, the capsules can be opened and the contents mixed with drink/food.1

Cautions for Cholic Acid

Contraindications

None.1

Warnings/Precautions

Exacerbation of Liver Impairment

Monitor liver function and discontinue cholic acid in patients who develop worsening of liver function while on treatment. Concurrent elevations of serum gamma glutamyltransferase (GGT), alanine aminotransferase (ALT) may indicate cholic acid overdose. Discontinue treatment with cholic acid at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis. 1

Evidence of liver impairment was present before treatment with cholic acid in approximately 86% (44/51) of patients with bile acid synthesis disorders due to SEDs and in approximately 50% (14/28) of patients with PDs including Zellweger spectrum disorders. Five of the patients (3 SED and 2 PD) with liver impairment at baseline experienced worsening serum transaminases, elevated bilirubin values, or worsening cholestasis on liver biopsy following treatment. An additional 5 patients (2 SED and 3 PD) who did not have baseline cholestasis experienced an exacerbation of their liver disease while on treatment. Exacerbation of liver impairment by cholic acid in these patients cannot be ruled out.1

Six patients with single enzyme defects underwent liver transplant, including four patients diagnosed with AKR1D1 deficiency, one with 3β-HSD deficiency, and one with CYP7A1 deficiency.1

Specific Populations

Pregnancy

There is a pregnancy surveillance program that monitors pregnancy outcomes in women exposed to cholic acid during pregnancy (COCOA Registry [ChOlbam: Child and mOther's heAlth]). Women who become pregnant during cholic acid treatment are encouraged to enroll. Patients or their health care provider should call 1-844-20C-OCOA or 1-844-202-6262 to enroll. 1

No studies in pregnant women or animal reproduction studies have been conducted with cholic acid. 1 Limited published case reports discuss pregnancies in women taking cholic acid for 3β-HSD deficiency resulting in healthy infants. These reports may not adequately inform the presence or absence of drug-associated risk with the use of cholic acid during pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.1

Lactation

Endogenous cholic acid is present in human milk. Clinical lactation studies have not been conducted to assess the presence of cholic acid in human milk, the effects of cholic acid on the breastfed infant, or the effects of cholic acid on milk production. There are no animal lactation data and no data from case reports available in the published literature. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for cholic acid and any potential adverse effects on the breastfed infant from cholic acid or from the underlying maternal condition.1

Pediatric Use

The safety and effectiveness of cholic acid have been established in pediatric patients 3 weeks of age and older for the treatment of bile acid synthesis disorders due to SEDs, and for adjunctive treatment of patients with PDs including Zellweger spectrum disorders who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption.1

Geriatric Use

Clinical studies of cholic acid did not include any patients aged 65 years and over. It is not known if elderly patients respond differently from younger patients.1

Hepatic Impairment

Discontinue treatment with cholic acid if liver function does not improve within 3 months of the start of treatment.1

Discontinue treatment with cholic acid at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.1

Common Adverse Effects

Most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

  • Bile Salt Efflux Pump (BSEP) Inhibitors (e.g., cyclosporine): Avoid concomitant use; if concomitant use is necessary, monitor serum transaminases and bilirubin.1

  • Bile Acid Resins and Aluminum-Based Antacids: 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 antacids.1

Actions

Cholic acid is a primary bile acid synthesized from cholesterol in the liver. In bile acid synthesis disorders due to SEDs in the biosynthetic pathway, and in PDs including Zellweger spectrum disorders, deficiency of primary bile acids leads to unregulated accumulation of intermediate bile acids and cholestasis. Bile acids facilitate fat digestion and absorption by forming mixed micelles, and facilitate absorption of fat-soluble vitamins in the intestine.1

Endogenous bile acids including cholic acid enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions. 1

Advice to Patients

Exacerbation of Liver Impairment

Advise patients that they will need to undergo laboratory testing periodically while on treatment to assess liver function.1

Advise patients that cholic acid may worsen liver impairment and that they should immediately report to their health care provider any symptoms associated with liver impairment (e.g., skin or the whites of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleeding or bruising occurs more easily than normal, or increased lethargy).1

Administration

Advise patients to take cholic acid with food.1

Advise patients to take cholic acid at least one hour before or 4 to 6 hours after taking a bile acid binding resin or an aluminum-based antacid.1

Advise patients not to crush or chew the capsules.1

For infants and children who cannot swallow capsules, the capsules can be opened and the contents mixed with either infant formula or expressed breast milk (for younger children), or soft food such as mashed potatoes or apple puree (for older children and adults) in order to mask any unpleasant taste: 1) Hold the capsule over the prepared liquid/food, gently twist open, and allow the contents to fall into the liquid/food. 2) Mix the entire capsule contents with one or two tablespoonfuls (15 mL to 30 mL) of infant formula, expressed breast milk, or soft food such as mashed potatoes or apple puree. 3) Stir for 30 seconds. 4) The capsule contents will remain as fine granules in the milk or food, and will not dissolve. 5) Administer the mixture immediately.1

Pregnancy Registry

Advise patients there is a pregnancy surveillance program that monitors pregnancy outcomes in women exposed to cholic acid during pregnancy.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Cholic Acid

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsule

50 mg

Cholbam

Manchester Pharmaceuticals

250 mg

Cholbam

Manchester Pharmaceuticals

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: September 14, 2016
Last reviewed: September 14, 2016
Date modified: October 12, 2016

References

1. Manchester Pharmaceuticals. Cholbam (Cholic Acid) ORAL prescribing information. 2015 Mar.

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