CHOLBAM

Orally administered cholic acid is subject to the same metabolic pathway as endogenous cholic acid. Cholic acid is absorbed by passive diffusion along the length of the gastrointestinal tract. Once absorbed, cholic acid enters into the body’s bile acid pool and undergoes enterohepatic circulation mainly in conjugated forms. In the liver, cholic acid is conjugated with glycine or taurine by bile acid-CoA synthetase and bile acid-CoA:amino acid N-acyltransferase. Conjugated cholic acid is actively...

14.1 Bile Acid Synthesis Disorders due to Single Enzyme Defects The effectiveness of CHOLBAM at dosages of 10 to 15 mg/kg per day in patients with SEDs was assessed in:

• Trial 1: a non-randomized, open-label, single-arm trial in 50 patients over an 18‑year period
• Trial 2: an extension trial of 12 new patients along with 21 patients who rolled over from Trial 1 (n=33 total). Efficacy data are available for 21 months of treatment.
• A published case series of 15 patients with SEDs and 3 patients with PDs. Enrollment criteria in Trials 1 and 2 were based on abnormal urinary bile acid by Fast A...

The following clinically significant adverse reaction is described elsewhere in the labeling:

• Exacerbation of Liver Impairment [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mirum Pharmaceuticals at 1-855-MRM-4YOU or FDA at 1-800-FDA-1088 or www.fda.gov/m...

None. None ( 4 )

Exacerbation of Liver Impairment: Monitor liver function. Discontinue CHOLBAM if liver function worsens while on treatment. ( 5.1 ) 5.1 Exacerbation of Liver Impairment In clinical trials, evidence of liver impairment was present before treatment with CHOLBAM 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 impairmen...

7 DRUG INTERACTIONS

• Bile Salt Efflux Pump (BSEP) Inhibitors (e.g., cyclosporine): Avoid concomitant use; if concomitant use is necessary, monitor serum transaminases and bilirubin ( 7.1 )
• 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. ( 2.3 , 7...