Usual Adult Dose for Bile Acid Synthesis Disorders

Initial dose: 10 to 15 mg/kg orally once a day or in 2 divided doses

Patients with Concomitant Familial Hypertriglyceridemia:
Initial dose: 11 to 17 mg/kg orally once a day or in 2 divided doses

Maintenance dose: The lowest dose that effectively maintains liver function

Comments:

• Adequacy of dosing should be determined by patient monitoring of clinical response and laboratory values; monitor more frequently during periods of rapid growth, concomitant disease, and pregnancy
• Concurrent elevations of serum gamma glutamyltransferase (GGT) and ALT may indicate cholic acid overdose.

• For the treatment of bile acid synthesis disorders due to single enzyme defects
• As 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.

Usual Pediatric Dose for Bile Acid Synthesis Disorders

Initial dose: 10 to 15 mg/kg orally once a day or in 2 divided doses

Patients with Concomitant Familial Hypertriglyceridemia:
Initial dose: 11 to 17 mg/kg orally once a day or in 2 divided doses

Maintenance dose: The lowest dose that effectively maintains liver function

Comments:

• Adequacy of dosing should be determined by patient monitoring of clinical response and laboratory values; monitor more frequently during periods of rapid growth, concomitant disease, and pregnancy
• Concurrent elevations of serum gamma glutamyltransferase (GGT) and ALT may indicate cholic acid overdose.

• For the treatment of bile acid synthesis disorders due to single enzyme defects
• As 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.

Renal Dose Adjustments

No data available

Liver Dose Adjustments

Use caution; patients are expected to present with some degree of hepatic impairment which should improve with treatment

• Discontinue treatment if liver function does not improve within 3 months of the start of treatment.
• Discontinue treatment if complete biliary obstruction develops.
• Interrupt treatment if at any time there are clinical or laboratory indicators of worsening liver function or cholestasis; may consider restarting treatment at a lower dose if liver function parameters return to baseline.

Dose Adjustments

Patients with Concomitant Familial Hypertriglyceridemia: Initial dose: 11 to 17 mg/kg orally once a day or in 2 divided doses

• Patients with newly diagnosed or a family history of, familial hypertriglyceridemia may have poor absorption of this drug from the intestine and require a 10% increase in the recommended dosage to account for losses due to malabsorption.

Precautions

Safety and efficacy have not been established in patients younger than 3 weeks of age.

Consult WARNINGS section for additional precautions.

Dialysis

No data available

Other Comments

OTHER COMMENTS:
Administration advice:

• Take with food
• Take at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid resin or aluminum-based antacid
• Capsules should not be crushed or chewed
• For patients unable to swallow capsules whole, capsules may be opened and mixed with 15 to 30 mL of infant formula, breast milk, soft food such a mashed potatoes or apple puree
• To prepare, hold capsule over liquid/food and gently twist open capsule and allow contents to fall; stir for 30 seconds; the capsule contents will not dissolve but remain as fine granules
• Administer mixture immediately

• Treatment should be initiated and monitored by an experienced hepatologist or pediatric gastroenterologist.
• The safety and effectiveness of this drug on extrahepatic manifestations of bile acid synthesis disorders due to single enzyme defects or peroxisomal disorders including Zellweger spectrum disorders have not been established.
• The utility of bile acid measurements in monitoring the clinical course of patients and in decisions regarding dose adjustment has not been demonstrated.

• Hepatic: Monitor AST, ALT serum gamma glutamyltransferase (GGT), alkaline phosphatase (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
• Monitor more frequently during periods of rapid growth, concomitant disease, and pregnancy

• Instruct patients to report any signs or symptoms of worsening liver impairment.
• Patients should speak to their physician or health care provider if they become pregnant, intend to become pregnant, or are breastfeeding.