Frequently asked questions
About CHOLBAM® (cholic acid)
When may CHOLBAM be appropriate?
CHOLBAM is a bile acid indicated for:
- Treatment of bile acid synthesis disorders due to single enzyme defects1
- Adjunctive treatment of peroxisomal disorders, including peroxisomal biogenesis disorder-Zellweger spectrum disorder (PBD‑ZSD), in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption.1
The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders, including PBD‑ZSD, have not been established.1
How does CHOLBAM work?
CHOLBAM works by increasing cholic acid levels. By increasing cholic acid in the hepatocyte, CHOLBAM is thought to suppress the production of the hepatotoxic atypical bile acids DHCA and THCA.2
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, 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.1
CHOLBAM may improve bile flow and increase solubilization of dietary fats and fat-soluble vitamins through emulsification.2
Why should I prescribe CHOLBAM?
Treatment with CHOLBAM may reduce hepatocyte exposure to DHCA and THCA and reduce liver injury. CHOLBAM may also increase intraluminal bile acid concentrations to improve absorption of fats and fat-soluble vitamins to facilitate weight gain.1,2
How do I dose CHOLBAM?
Starting dose of CHOLBAM for both children and adults should be based on weight. The recommended dose of CHOLBAM is 10 to 15 mg/kg once a day, which can be divided into 2 doses if necessary.1
Please see the CHOLBAM Prescribing Information for dose modification instructions for patients with newly diagnosed, or a family history of familial hypertriglyceridemia, treatment monitoring guidelines, and administration instructions.
How is CHOLBAM administered?
CHOLBAM should be taken with food. For infants and children who cannot swallow capsules, CHOLBAM capsules can be opened and mixed with either infant formula or breast milk (for younger children), or soft food such as mashed potatoes or apple puree (for older children and adults) in order to mask any unpleasant taste.1
How should I monitor patients taking CHOLBAM?
Monitor AST, ALT, serum GGT, ALP, bilirubin, and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the subsequent 3 years, and annually thereafter. Learn more about monitoring.1
What are potential adverse events with CHOLBAM?
In the CHOLBAM clinical trials, diarrhea was the most common adverse reaction in approximately 2% of the patient population. All other adverse reactions occurred in ≤1% of the patient population.1 See more safety information.
Testing
What test can confirm diagnosis of PBD‑ZSD?
Early diagnosis and treatment are important to help reduce the risk of liver damage.
In partnership with PreventionGenetics, Mirum Pharmaceuticals offers a no-cost genetic testing program for qualifying patients to help identify PBD‑ZSD, a rare autosomal recessive disorder caused by mutations in one of 13 PEX genes and characterized by an impaired peroxisome assembly, leading to multiple enzyme deficiencies.3,5 Learn more about this test.
What test can determine the extent of liver involvement in PBD‑ZSD patients?
Mirum Pharmaceuticals has partnered with Cincinnati Children’s Hospital Medical Center to offer a liquid chromatography–mass spectrometry analysis of bile acid profile at no cost to qualifying patients.
This test will help identify the presence and concentration levels of DHCA/THCA, atypical bile acids that can be hepatotoxic and associated with liver disease. Learn more about this test.
Peroxisomal biogenesis disorder-Zellweger spectrum disorder (PBD‑ZSD)
What is peroxisomal biogenesis disorder-Zellweger spectrum disorder (PBD‑ZSD)?
PBD‑ZSD is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation, affecting multiple metabolic and biosynthetic processes. PBD‑ZSD is caused by pathogenic variants in one of 13 PEX genes.3-5
Previously regarded as 3 distinct disorders, PBD‑ZSD is now considered to comprise 1 disease that ranges in phenotype from severe (previously referred to as Zellweger syndrome) to moderate (previously referred to as neonatal adrenoleukodystrophy or NALD) to mild (previously referred to as infantile Refsum disease or IRD).6,7
How does PBD‑ZSD present?
In affected patients, the severity and range of signs and symptoms vary according to subgroup, based on age at presentation. Signs and symptoms also can vary by patient within severity subgroups, ie, not every patient will present the same way, even if they are grouped as all severe, all moderate, or all mild.3,6
Patients with milder signs and symptoms may have a delay in diagnosis, as these signs and symptoms may not appear abnormal to parents. In addition, many other diseases present similarly. Overall, common presenting signs include developmental delay and other neurologic abnormalities, vision impairment (due to retinal degeneration), sensorineural hearing loss, and evidence of liver disease.3,7-9
Patient Resources
What is the Mirum Access Plus Support Program?
Mirum Access Plus is available to help you, your office, and your patient not only get started with CHOLBAM after you’ve prescribed it, but also to provide support throughout treatment. Learn more about this valuable program.
If you have any questions about Mirum Access Plus, contact us at 1-855-MRM-4YOU (1-855-676-4968) Monday through Friday, 8:00 AM through 8:00 PM ET.
How do I enroll my patients?
If you’d like to prescribe CHOLBAM for your patient, download the Patient Enrollment Form. Once you have filled out the form and/or have your patient consent for Mirum Access Plus services, fax it to 1-855-282-4884.
REFERENCES: 1. CHOLBAM. Prescribing information. Mirum Pharmaceuticals, Inc. 2. Berendse K, Klouwer FCC, Koot BGP, et al. Cholic acid therapy in Zellweger spectrum disorders. J Inherit Metab Dis. 2016;39(6):859-868. doi: 10.1007/s10545-016-9962-9 3. Braverman NE, Raymond GV, Rizzo WB, et al. Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016:117(3):313-321. doi: 10.1016/j.ymgme.2015.12.009 4. Jansen RLM, Santana-Molina C, van den Noort M, Devos DP, van der Klei IJ. Comparative genomics of peroxisome biogenesis proteins: making sense of the PEX proteins. Front Cell Dev Biol. 2021;9:654163. doi:10.3389/fcell.2021.654163 5. Waterham HR, Ebberink MS. Genetics and molecular basis of human peroxisome biogenesis disorders. Biochim Biophys Acta. 2012;1822(9):1430-1441. doi:10.1016/j.bbadis.2012.04.006 6. Klouwer FCC, Berendse K, Ferdinandusse S, Wanders RJA, Engelen M, Poll-The BT. Zellweger spectrum disorders: clinical overview and management approach. Orphanet J Rare Dis. 2015;10:151. doi: 10.1186/s13023-015-0368-9 7. Braverman NE, D’Agostino MD, Maclean GE. Peroxisome biogenesis disorders: biological, clinical and pathophysiological perspectives. Dev Disabil Res Rev. 2013;17(3):187-196. doi: 10.1002/ddrr.1113 8. Zellweger H, Maertens P, Superneau D, Wertelecki W. History of the cerebrohepatorenal syndrome of Zellweger and other peroxisomal disorders. South Med J. 1988;81(3):357-364. doi: 10.1097/00007611-198803000-00017 9. Poll-The BT, Saudubray JM, Ogier HA, et al. Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy. Eur J Pediatr. 1987;146:477-483. doi: 10.1007/BF00441598
INDICATION
CHOLBAM® (cholic acid) 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 exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption.
LIMITATIONS OF USE
The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders, including Zellweger spectrum disorders, have not been established.IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS – Exacerbation of liver impairment
- Monitor liver function and discontinue CHOLBAM in patients who develop worsening of liver function while on treatment.
- Concurrent elevations of serum gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) may indicate CHOLBAM overdose.
- Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis.
ADVERSE REACTIONS
- The most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.
DRUG INTERACTIONS
- Inhibitors of Bile Acid Transporters: Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.
- Bile Acid Binding Resins: Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of CHOLBAM. 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.
- Aluminum-Based Antacids: Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid.
PREGNANCY
No studies in pregnant women or animal reproduction studies have been conducted with CHOLBAM.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. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CHOLBAM and any potential adverse effects on the breastfed infant from CHOLBAM or from the underlying maternal condition.GERIATRIC USE
It is not known if elderly patients respond differently from younger patients.HEPATIC IMPAIRMENT
- Discontinue treatment with CHOLBAM if liver function does not improve within 3 months of the start of treatment.
- Discontinue treatment with CHOLBAM at any time if there are clinical or laboratory indicators of worsening liver function or cholestasis. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.