Testing for bile acid synthesis disorders
How are bile acid synthesis disorders diagnosed?
To find out if a patient has Bile Acid Synthesis Disorder, the doctor will probably begin by taking a medical history and doing a physical exam. In addition, he or she may do1-5:
- Blood and urine tests, including:
- Direct bilirubin
- Alanine transaminase (ALT)/aspartate transaminase (AST)
- Gamma glutamyltransferase (GGT)
- Primary bile acids
- Confirmation by one of the following:
- Mass spectrometry test or
- Genetic testing using a panel of DNA that represents a diverse array of genes that may cause cholestasis
Early diagnosis and treatment are very important
If left untreated, Bile Acid Synthesis Disorders can cause liver damage and eventually the liver may no longer work normally and a liver transplant may be necessary. It is important to diagnose and treat Bile Acid Synthesis Disorders as early as possible, since untreated patients may develop serious liver disease/liver failure.1
Early identification and initiation of therapy may lead to better outcomes.1,6
Bile acid synthesis disorders should be
diagnosed as early as possible
Talk to your doctor about treatment options
Bile Acid Synthesis Disorders cannot be treated by lifestyle changes. One of the primary bile acids normally produced in the liver is called cholic acid. Since patients with Bile Acid Synthesis Disorders do not properly produce this substance, they are given cholic acid as a replacement therapy. This can help restore normal liver function.6
FREE Genetic Screening for Cholestasis for Qualifying Patients
Retrophin is committed to providing support to patients, families and caregivers. Retrophin is offering patients free genetic testing to help find potentional causes of cholestasis. Your doctor can gain access to this program by visiting testcholestasis.com. We encourage you to speak to your doctor about this test and whether or not you may be a candidate.
FREE Atypical Bile Acid Test for Cholestasis for Qualifying Patients
Has your child been tested for toxic or harmful bile acids associated with causing cholestasis? The atypical bile acid test is not a routine test your doctor has likely run. This simple urine test is important to consider if your child has cholestasis or unexplained liver disease. Retrophin is invested in the well-being of patients with bile acid synthesis disorders and has partnered with Cincinnati Children's Hospital Medical Center to offer a free laboratory test. Download the Atypical Bile Acid Test form and talk to your child’s physician about running this important test.
Bile Acid Synthesis Disorders CCHMC Free Testing Program Patient Overview
1. Heubi JE, Setchell K, Bove KE. Inborn errors of bile acid metabolism. Semin Liver Dis. 2007;27(3):282-294. 2. Moyer V, Freese DK, Whitington PF, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2004;39:115-128. 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. 4. McKiernan PJ. Neonatal cholestasis. Semin Neonatol. 2002;7:153-165. 5. Fischler B, Lamireau T. Cholestasis in the newborn and infant. Clin Res Hepatol Gastroenterol. 2014;38:263-267. 6. Setchell KD, Heubi JE. Defects in bile acid biosynthesis—diagnosis and treatment. J Pediatr Gastroenterol Nutr. 2006;43:S17-S22.
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.
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.
- 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.
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.
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.
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.