Cholic acid
Indications
Cholic acid is used for:
Bile Acid Synthesis Disorders, Peroxisomal Disorders
Adult Dose
Bile Acid Synthesis Disorders
Indicated for bile acid synthesis disorders due to single-enzyme defects (SEDs)
10-15 mg/kg/day PO qDay or divided BID
Peroxisomal Disorders
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
Child Dose
Bile Acid Synthesis Disorders
Indicated for bile acid synthesis disorders due to single-enzyme defects (SEDs)
<3 weeks: Safety and efficacy not established
>3 weeks: 10-15 mg/kg/day PO qDay or divided BID
Peroxisomal Disorders
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
<3 weeks: Safety and efficacy not established
>3 weeks: 10-15 mg/kg/day PO qDay or divided BID
Renal Dose
Administration
Take with food
Take at least 1 hr before or 4-6 hr (or at as great an interval as possible) after a bile acid binding resin (eg, cholestyramine) or aluminum-based antacid
Contra Indications
Precautions
Monitor liver function and discontinue at any time there are clinical or laboratory indicators of worsening liver function or cholestasis
Concurrent elevations of GGT and ALT may indicate overdose; discontinue (see Dosage Modifications)
Evidence of liver impairment was present before treatment with cholic acid in ~86% of patients with bile acid synthesis disorders due to SEDs and in ~50% of patients with PDs, including Zellweger spectrum disorders
Pregnancy-Lactation
Pregnancy
No studies in pregnant women or animal reproduction studies have been conducted
Limited published case reports discuss pregnancies in women taking cholic acid for 3beta-HSD deficiency, resulting in healthy infants
Lactation
Endogenous cholic acid is present in human milk
Clinical lactation studies have not been conducted to assess the presence of Cholbam in human milk, the effects on the breastfed infant, or the effects on milk production
There are no animal lactation data and no data from case reports available in the published literature
Interactions
Adverse Effects
Side effects of Cholic acid :
1-10%
Diarrhea (2%)
Reflux esophagitis (1%)
Malaise (1%)
Jaundice (1%)
Skin lesion (1%)
Nausea (1%)
Abdominal pain (1%)
Intestinal polyp (1%)
Urinary tract infection (1%)
Peripheral neuropathy (1%)
Mechanism of Action
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 they facilitate absorption of fat-soluble vitamins in the intestine
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