Safety

Possible side effects of CHOLBAM® (cholic acid) capsules

CHOLBAM® has been proven to be safe and effective with over 18 years of clinical trial experience.

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

Call your doctor right away if there is

  • Yellowing of the skin or whites of the eyes
  • Dark or brown (tea-colored) urine
  • Pain on the right side of the stomach
  • Bleeding or bruising that occurs more easily than normal
  • Increased tiredness

Monitor liver function
Patients taking CHOLBAM® will need to undergo laboratory testing periodically while on treatment to assess liver function.

Most Common Adverse Reactions in Trials 1 and 2*
Adverse Reactions Trial 1 Trial 2** Overall (%)
Diarrhea 1 2** 3 (2%)
Reflux esophagitis 1 0 1 (1%)
Malaise 1 0 1 (1%)
Jaundice 1 0 1 (1%)
Skin lesion 1 0 1 (1%)
Nausea 0 1** 1 (1%)
Abdominal pain 0 1** 1 (1%)
Intestinal polyp 0 1** 1 (1%)
Urinary tract infection 0 1** 1 (1%)
Peripheral neuropathy 0 1** 1 (1%)

*There were 12 adverse reactions reported across 9 patients in the trials

**Adverse reactions that occurred in new patients

CHOLBAM® (cholic acid) capsules, for oral use [prescribing information]. San Diego, CA: Retrophin, Inc.; March 2015.

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 Retrophin, Inc. at 1-877-659-5518 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.