Therapy

Treating bile acid synthesis disorders due to single enzyme defects with CHOLBAM® (cholic acid) capsules

Effect of cholic acid on biochemical parameters

Effect of cholic acid and ursodeoxycholic acid on biochemical parameters
Liver biochemistry results normalized in all patients (N=15) treated with CHOLBAM® and remained normal through follow-up.2,3

  • Median follow-up with treatment was 12.4 years (range, 5.6-15 years)
  • Patients (n=8) were on ursodeoxycholic acid (UDCA) prior to diagnosis of Bile Acid Synthesis Disorders

ALT, alanine transaminase; CA, cholic acid; UDCA, ursodeoxycholic acid

Cholic acid

In a published case series (n=15) with Bile Acid Synthesis Disorders due to Single Enzyme Defects2,3

  • 8 patients received UDCA initially prior to diagnosis of Bile Acid Synthesis Disorders but were switched to CA upon diagnosis
    • 7 patients were started immediately on CA
    • Median duration of CA treatment was 12.4 years (range 5.6 to 15 years)
  • After cholic acid treatment, biochemical parameters normalized in all patients and remained normal at follow-up
  • Unlike ursodeoxycholic acid, cholic acid is an farnesoid X receptor (FXR) agonist
    • Provides physiological feedback
    • Suppresses the production of hepatotoxic atypical bile acids

1. Setchell KDR. Adolf Windaus Prize Lecture 2004. Defects in bile acid synthesis—specific and treatable causes of metabolic liver disease. In: Paumgartner G et al, eds. Bile Acid Biology and Its Therapeutic Implications. Proceedings of the Falk Symposium 141 (XVIII Internationale Bile Acid Meeting) held in Stockholm, Sweden, June 18-19, 2004. Netherlands: Springer; 2005:1-15. 2. CHOLBAM® (cholic acid) capsules, for oral use [prescribing information]. San Diego, CA: Travere Therapeutics, Inc.; March 2015. 3. Gonzales E, Gerhardt MF, Fabre M, et al. Oral cholic acid for hereditary defects of primary bile acid synthesis: a safe and effective long-term therapy. Gastroenterology. 2009;137(4):1310-1320.

Indication and Usage
CHOLBAM® is a bile acid indicated for:

  • Treatment of bile acid synthesis disorders due to single enzyme defects
  • Adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who show signs and symptoms of liver disease, steatorrhea (fatty stools), or complications from decreased fat soluble vitamins absorption (A, D, E, K)

Limitation of Use:
The safety and effectiveness of CHOLBAM® on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorder including Zellweger spectrum disorders have not been established.

Important Safety Information
Warnings and Precautions—Exacerbation of Liver Impairment

  • Monitor liver function and discontinue CHOLBAM® (cholic acid) in patients who develop worsening of liver function while on treatment.
  • Monitor AST, ALT, GGT, alkaline phosphatase, bilirubin, and international normalized ratio (INR) every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the next 3 years and annually thereafter. Administer the lowest dose that effectively maintains liver function.
  • Discontinue CHOLBAM® 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.

Adverse Reactions
In the CHOLBAM® clinical trials, diarrhea was the most common adverse reaction in approximately 2% of the patient population. All other adverse reactions are less than or equal to 1% of the patient population.

Drug Interaction

  • Bile Salt Efflux Pump (BSEP) Inhibitors (eg, cyclosporine): Avoid concomitant use; if concomitant use is necessary, monitor serum transaminases and bilirubin.
  • Bile Acid Resins and Aluminum-Based Antacids: Take CHOLBAM® 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.

Pregnancy
No studies in pregnant women or animal reproduction studies have been conducted with CHOLBAM®. Women who become pregnant during CHOLBAM® treatment are encouraged to call 1-844-202-6262.

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 of CHOLBAM® on the breastfed infant, or the effects of CHOLBAM® on milk production.

There are no animal lactation data and no data from case reports available in the published literature.

Overdosage
In the event of overdose (elevated GGT and ALT), the patient should be monitored and treated symptomatically.

Elevated serum gamma glutamyltransferase (GGT) and serum alanine aminotransferase (ALT) may indicate CHOLBAM® overdose. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

Please see full prescribing information for CHOLBAM® (cholic acid) 50 mg and 250 mg capsules.

To report SUSPECTED ADVERSE REACTIONS, contact Travere Therapeutics, Inc. at 1-877-659-5518 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.