Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Cholbam: 50 mg, 250 mg
Pharmacology
Mechanism of Action
Cholic acid, a primary bile acid, enhances bile flow and provides the physiologic feedback inhibition of bile acid synthesis to maintain bile acid homeostasis.
Pharmacokinetics/Pharmacodynamics
Absorption
Absorbed by passive diffusion along the gastrointestinal tract. Patients with concomitant familial hypertriglyceridemia may have poor absorption.
Metabolism
Hepatic; conjugated by bile acid- enzymes. Conjugated cholic acid is secreted into bile. It is reabsorbed in the ileum, and enters another cycle of enterohepatic circulation.
Excretion
Feces
Use: Labeled Indications
Bile acid synthesis disorders: Treatment of bile acid synthesis disorders due to single enzyme defects (SEDs).
Peroxisomal disorders: Treatment (adjunctive) of peroxisomal disorders (PDs), including Zellweger spectrum disorders, in patients who exhibit manifestations of hepatic disease, steatorrhea, or complications from decreased fat soluble vitamin absorption.
Limitations of use: The safety and effectiveness of cholic acid on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs, including Zellweger spectrum disorders, have not been established.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Bile acid synthesis disorders, peroxisomal disorders: Oral: 10 to 15 mg/kg (once daily or in 2 divided doses); administer 11 to 17 mg/kg (once daily or in 2 divided doses) in patients with concomitant familial hypertriglyceridemia.
Dosing: Pediatric
Bile acid synthesis disorders or peroxisomal disorders (eg, Zellweger spectrum disorders): Infants, Children, and Adolescents: Oral: 10 to 15 mg/kg/day once daily or in divided doses twice daily; round dose to nearest available capsule sizes (50 mg or 250 mg). Allow 3 months of treatment to assess therapeutic effect (eg, clinical response parameters: LFTs, bilirubin, PT/INR, steatorrhea); use the lowest dose that effectively maintains liver function; discontinue if hepatic function does not improve within 3 months of starting treatment.
Dosing adjustment for familial hypertriglyceridemia (including newly diagnosed or family history of): Note: Patients with hypertriglyceridemia have malabsorption of cholic acid requiring 10% higher doses: Infants, Children, and Adolescents: Oral: 11 to 17 mg/kg/day once daily or in divided doses twice daily; round dose to nearest available capsule sizes (50 mg or 250 mg).
Administration
Oral: Administer (once daily or in 2 divided doses) with food at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after bile acid binding resin or aluminum-based antacid. Do not crush or chew.
For patients unable to swallow capsules, may mix the entire capsule contents with 15 mL to 30 mL of infant formula, expressed breast milk, or soft food such as mashed potatoes or apple puree. Stir for 30 seconds. Capsule contents will remain as fine granules in the milk or food, and will not dissolve. Administer the mixture immediately.
Dietary Considerations
Administer with food.
Storage
Store at 20°C to 25°C (69°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Drug Interactions
Aluminum Hydroxide: May decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 hour before or 4 to 6 hours after administration of any aluminum hydroxide-containing products to minimize the potential for a significant interaction. Consider therapy modification
Bile Acid Sequestrants: May decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 to 4 hours before or 4 to 6 hours after administration of any bile acid-binding products to minimize the potential for a significant interaction. Consider therapy modification
BSEP/ABCB11 Inhibitors: May decrease the excretion of Cholic Acid. Avoid combination
Sevelamer: May decrease the absorption of Cholic Acid. Management: Administer cholic acid at least 1 hour before or 4 to 6 hours after administration of any bile acid-binding products, such as sevelamer, to minimize the potential for a significant interaction. Consider therapy modification
Sucralfate: May decrease the absorption of Cholic Acid. Consider therapy modification
Adverse Reactions
>10%:
Gastrointestinal: Cholestasis (≤14%, exacerbation)
Hepatic: increased serum bilirubin ( ≤14%), increased serum transaminases ( ≤14%)
1% to 10%:
Central nervous system: Malaise (≤1%), peripheral neuropathy (≤1%)
Dermatologic: Skin lesion (≤1%)
Gastrointestinal: Diarrhea (1% to 2%), abdominal pain (≤1%), intestinal polyps (≤1%), nausea (≤1%), reflux esophagitis (≤1%)
Genitourinary: Urinary tract infection (≤1%)
Hepatic: Hepatic disease (6%, exacerbation), jaundice (≤1%)
<1%, postmarketing, and/or case reports: Cholelithiasis (3β-HSD deficient patient)
Warnings/Precautions
Disease-related concerns:
- Hepatic impairment: Monitor liver function tests (eg, aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], bilirubin and INR) monthly for the first 3 months. Discontinue if hepatic 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 hepatic function or cholestasis; continue to monitor hepatic function and consider restarting a lower dose when parameters return to baseline. Concurrent elevations of GGT and ALT may indicate cholic acid overdose.
Other warnings/precautions:
- Experienced physician: Treatment should be initiated and monitored by an experienced hepatologist or pediatric gastroenterologist.
Monitoring Parameters
Monitor AST, ALT, 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 next three years, and annually thereafter. Monitor more frequently during periods of rapid growth, concomitant disease, and pregnancy.
Pregnancy
Pregnancy Considerations
Animal reproduction studies have not been conducted. Information related to the use of cholic acid during pregnancy is limited. Tests of hepatic function should be monitored closely.
A registry is available for women exposed to cholic acid during pregnancy. Patients or their health care provider should call 844-202-6262 to enroll.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
