Cholic acid

Bile Acid Synthesis Disorders, Peroxisomal Disorders

Bile Acid Synthesis Disorders Indicated for bile acid synthesis disorders due to single-enzyme defects (SEDs) 10-15 mg/kg/day PO once daily 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 10-15 mg/kg/day PO once daily or divided BID

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 once daily 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 once daily or divided BID

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

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 In patients with cirrhosis, cases of severe hepatotoxicity observed following postmarket use of therapy; exacerbation of liver impairment in these patients cannot be ruled out MONITORING PARAMETERS Monitor liver function and discontinue at any time there are clinical or laboratory indicators of worsening liver function or cholestasis 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. Monitor serum and/or urine bile-acid concentrations every 3 months for the first year, then every 6 months for three years, then annually.

Not Classi 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 The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Bile Salt Efflux Pump (BSEP) Inhibitors (e.g., cyclosporine): Avoid concomitant use; if concomitant use is necessary, monitor serum transaminases and bilirubin 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. Contraindicated (0) Serious (2) atazanavir felodipine

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%)

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