Dosage Regimen for Bile Acid Synthesis Disorders Due to SEDs and PDs Including Zellweger Spectrum Disorders

The recommended dosage of CHOLBAM is 10 to 15 mg/kg administered orally once daily, or in two divided doses, in pediatric patients and in adults.

Tables 1 and 2 show the number of capsules that should be administered daily to approximate a dosage of 10 mg/kg/day and 15 mg/kg/day, respectively, using the available 50 mg and 250 mg capsules alone or in combination.

Patients with newly diagnosed, or a family history of, familial hypertriglyceridemia may have poor absorption of CHOLBAM from the intestine and require a 10% increase in the recommended dosage to account for losses due to malabsorption. The recommended dosage of CHOLBAM in patients with concomitant familial hypertriglyceridemia is 11 to 17 mg/kg orally once daily, or in two divided doses. Adequacy of the dosage regimen can be determined by monitoring the patient’s clinical response including steatorrhea and laboratory values of serum transaminases, bilirubin, and prothrombin time/international normalized ratio (PT/INR).

Treatment Monitoring

Treatment with CHOLBAM should be initiated and monitored by an experienced hepatologist or pediatric gastroenterologist.

Monitor serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), serum gamma glutamyltransferase (GGT), alkaline phosphatase, bilirubin, and INR every month for the first 3 months, every 3 months for the next 9 months, every 6 months during the subsequent three years, and annually thereafter. Monitor more frequently during periods of rapid growth, concomitant disease, and pregnancy. Administer the lowest dose of CHOLBAM that effectively maintains liver function [see Warnings and Precautions (5.1)].

Discontinue treatment with CHOLBAM if liver function does not improve within 3 months of the start of treatment or if complete biliary obstruction develops.

Discontinue treatment with CHOLBAM at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis [see Warnings and Precautions (5.1)].

Concurrent elevations of serum GGT and serum ALT may indicate CHOLBAM overdose [see Overdosage (10)]. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

Assessment of serum or urinary bile acid levels using mass spectrometry is used in the diagnosis of bile acid synthesis disorders due to SEDs and PDs including Zellweger spectrum disorders. The utility of bile acid measurements in monitoring the clinical course of patients and in decisions regarding dose adjustment has not been demonstrated.

Administration Instructions

• Take CHOLBAM with food.
• 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 antacid.
• Do not crush or chew the capsules.
• For patients unable to swallow the capsules, open the capsules and mix the contents with infant formula or expressed 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. Hold the capsule over the prepared liquid/food, gently twist open, and allow the contents to fall into the liquid/food.
  2. Mix the entire capsule contents with one or two tablespoons (15 mL to 30 mL) of infant formula, expressed breast milk, or soft food such as mashed potatoes or apple puree.
  3. Stir for 30 seconds.
  4. The capsule contents will remain as fine granules in the milk or food and will not dissolve.
  5. Administer the mixture immediately