Dosing and uses of Cholbam (cholic acid)
Adult dosage forms and strengths
capsule
- 50mg
- 250mg
Bile Acid Synthesis Disorders
Indicated for bile acid synthesis disorders due to single-enzyme defects (SEDs)
10-15 mg/kg/day PO qDay or divided BId
Peroxisomal Disorders
Indicated for adjunctive treatment of peroxisomal disorders (PDs), including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption
10-15 mg/kg/day PO qDay or divided BId
Dosage modifications
Familial hypertriglyceridemia
- Patients with newly diagnosed or a family history of familial hypertriglyceridemia may have poor absorption of cholic acid from the intestine and require a 10% increase in the recommended dosage to account for losses due to malabsorption
- Recommended dosage range: 11-17 mg/kg/day PO qDay or divided BID
- Determine adequacy of the dosage regimen by monitoring clinical response, including steatorrhea, and laboratory values, including transaminases, bilirubin, and PT/INR
Dosing Considerations
Safety and effectiveness on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs have not been established
Monitoring
- Monitor AST, ALT, 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 3 yr; and annually thereafter
- Monitor more frequently during periods of rapid growth, concomitant disease, or pregnancy
- Administer the lowest dose that effectively maintains liver function
- Discontinue treatment if liver function does not improve within 3 months of the start of treatment or complete biliary obstruction develops
- Discontinue treatment at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis
- Concurrent elevations of GGT and ALT may indicate overdose; continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline
- Serum or urinary bile acid level 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
Pediatric dosage forms and strengths
capsule
- 50mg
- 250mg
Bile Acid Synthesis Disorders
Indicated for bile acid synthesis disorders due to single-enzyme defects (SEDs)
<3 weeks: Safety and efficacy not established
≥3 weeks: 10-15 mg/kg/day PO qDay or divided BId
Peroxisomal Disorders
Indicated for adjunctive treatment of peroxisomal disorders (PDs), including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption
<3 weeks: Safety and efficacy not established
≥3 weeks: 10-15 mg/kg/day PO qDay or divided BId
Dosage modifications
Familial hypertriglyceridemia
- Patients with newly diagnosed or a family history of familial hypertriglyceridemia may have poor absorption of cholic acid from the intestine and require a 10% increase in the recommended dosage to account for losses due to malabsorption
- Recommended dosage range: 11-17 mg/kg/day PO qDay or divided BID
- Determine adequacy of the dosage regimen by monitoring clinical response, including steatorrhea, and laboratory values, including transaminases, bilirubin, and PT/INR
Dosing Considerations
Safety and effectiveness on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs have not been established
Monitoring
- Monitor AST, ALT, 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 3 yr; and annually thereafter
- Monitor more frequently during periods of rapid growth, concomitant disease, or pregnancy
- Administer the lowest dose that effectively maintains liver function
- Discontinue treatment if liver function does not improve within 3 months of the start of treatment or complete biliary obstruction develops
- Discontinue treatment at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis
- Concurrent elevations of GGT and ALT may indicate overdose; continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline
- Serum or urinary bile acid level 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
Cholbam (cholic acid) adverse (side) effects
1-10%
Diarrhea (2%)
Reflux esophagitis (1%)
Malaise (1%)
Jaundice (1%)
Skin lesion (1%)
Nausea (1%)
Abdominal pain (1%)
Intestinal polyp (1%)
Urinary tract infection (1%)
Peripheral neuropathy (1%)
Warnings
Contraindications
None
Cautions
Monitor liver function and discontinue at any time there are clinical or laboratory indicators of worsening liver function or cholestasis
Concurrent elevations of GGT and ALT may indicate overdose; discontinue (see Dosage modifications)
Evidence of liver impairment was present before treatment with cholic acid in ~86% of patients with bile acid synthesis disorders due to SEDs and in ~50% of patients with PDs, including Zellweger spectrum disorders
Pregnancy and lactation
Pregnancy
No studies in pregnant women or animal reproduction studies have been conducted
Limited published case reports discuss pregnancies in women taking cholic acid for 3beta-HSD deficiency, resulting in healthy infants
COCOA Registry (ChOlbam: Child and mOther's heAlth)
- Women who become pregnant during treatment are encouraged to enroll
- Patients or their healthcare provider should call 1-844-20C-OCOA or 1-844-202-6262
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 on the breastfed infant, or the effects on milk production
There are no animal lactation data and no data from case reports available in the published literature
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Cholbam (cholic acid)
Mechanism of action
Cholic acid is a primary bile acid synthesized from cholesterol in the liver
In bile acid synthesis disorders due to SEDs in the biosynthetic pathway and in PDs, including Zellweger spectrum disorders, deficiency of primary bile acids leads to unregulated accumulation of intermediate bile acids and cholestasis
Bile acids facilitate fat digestion and absorption by forming mixed micelles, and they facilitate absorption of fat-soluble vitamins in the intestine
Endogenous bile acids, including cholic acid, enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis
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, farnesoid X 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
Absorption
Cholic acid is absorbed by passive diffusion along the length of the GI tract
Once absorbed, cholic acid enters into the body’s bile acid pool and undergoes enterohepatic circulation mainly in conjugated forms
Metabolism
In the liver, cholic acid is conjugated with glycine or taurine by bile acid-CoA synthetase and bile acid-CoA: amino acid N-acetyltransferase
Conjugated cholic acid is actively secreted into bile mainly by the bile salt efflux pump (BSEP) and then released into the small intestine, along with other components of bile
Conjugated cholic acid is mostly reabsorbed in the ileum mainly by the apical-sodium-dependent-bile acid transporter, passed back to the liver by transporters including sodium-taurocholate cotransporting polypeptide and organic anion transport protein, and enters another cycle of enterohepatic circulation
Elimination
Any conjugated cholic acid not absorbed in the ileum passes into the colon and may be reabsorbed in the colon or excreted in the feces
Administration
Instructions
Take with food
Take at least 1 hr before or 4-6 hr (or at as great an interval as possible) after a bile acid binding resin (eg, cholestyramine) or aluminum-based antacid
Do not crush or chew the capsules
Unable to Swallow Capsules
Capsules can be opened and the contents mixed with either 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
Mix with soft food or liquid
- Hold the capsule over the prepared liquid/food, gently twist open, and allow the contents to fall into the liquid/food
- Mix the entire capsule contents with 1-2 tablespoons (ie, 15-30 mL) of infant formula, expressed breast milk, or soft food (eg, mashed potatoes, applesauce)
- Stir for 30 seconds
- The capsule contents will remain as fine granules in the milk or food and will not dissolve
- Administer mixture immediately
Storage
Store at room temperature 20-25°C (69-77°F)
Excursions permitted from 15-30°C (59-86°F)
