General

Pronunciation:
koe-lik as-id

Trade Name(s)

• Cholbam

Ther. Class.

orphan drugs

Pharm. Class.

bile acid replacements

Indications

• Treatment of bile acid synthesis disorders caused by single enzyme defects.
• Adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorders associated with manifestations of liver disease, steatorrhea, or complications from decreased fat-soluble vitamin absorption.

Action

Cholic acid is the primary bile produced by the liver from cholesterol. Genetic deficiency of primary bile acids result in accumulation of intermediate bile acids and cholestasis. Bile acids facilitate fat digestion and absorption, facilitate absorption of fat-soluble vitamins, enhance bile flow, and regulate feedback inhibition of bile acid synthesis. Deficiencies result in progressive hepatic damage.

Therapeutic Effect(s):

Stable/improved hepatic parameters, ↑ weight, and improved survival.

Pharmacokinetics

Absorption: Absorbed by passive diffusion along the entire GI tract (absorption may be ↓ in newly diagnosed/family history of familial hypertriglyceridemia).

Distribution: Unknown.

Metabolism and Excretion: Enters into the bile acid pool, is conjugated in the liver, undergoes enterohepatic circulation, and is actively secreted into bile and then released into the small intestine and enters another cycle of enterohepatic circulation. Some is reabsorbed in the colon; some is fecally eliminated.

Half-life: Unknown.

TIME/ACTION PROFILE

Contraindication/Precautions

Contraindicated in:

• None.

Use Cautiously in:

• Worsening of liver function (discontinue/re-evaluate treatment);
• OB:  Safety not established in pregnancy;
• Lactation: Safety not established during breastfeeding;
• Pedi:  Children <3 mo (safety and effectiveness not established).

Adverse Reactions/Side Effects

Derm: skin lesions

GI: abdominal pain, diarrhea, exacerbation of liver impairment, intestinal polyps, nausea, reflux esophagitis

Neuro: malaise, peripheral neuropathy

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Bile salt efflux pump inhibitors, including  cyclosporine, exacerbate liver impairment; avoid concurrent use. If concurrent use unavoidable, monitor liver function carefully.
•  Bile acid resins  and  aluminum-based antacids  may ↓ absorption and effectiveness; administer cholic acid ≥1 hr before or ≥4–6 hr after.

Route/Dosage

PO (Adults and Children): 10–15 mg/kg once daily or in two divided doses; Concomitant familial hypertriglyceridemid: 11–17 mg/kg once daily or in two divided doses. Use lowest dose that maintains liver function without further impairment; discontinue if there is no improvement in 3 mo or if deterioration occurs.

Availability

Capsules: 50 mg, 250 mg

Assessment

• Assess patient for signs and symptoms of worsening liver impairment periodically during therapy.

Lab Test Considerations:

Monitor AST, ALT, GGT, alkaline phosphatase, bilirubin, and INR every mo for first 3 mo, every 3 mo for next 9 mo, every 6 mo during next three yr, and annually thereafter. Discontinue cholic acid if liver function does not improve within 3 mo of starting treatment, if complete biliary obstruction develops, or if persistent clinical or laboratory indicators of worsening liver function or cholestasis occur. Continue to monitor liver function and consider restarting a lower dose when parameters return to baseline.

Implementation

• PO Administer once or twice daily with food.  DNC: Swallow capsules whole; do not crush or chew.  If needed, capsules can be opened and contents mixed with food or drink (15–30 mL of infant formula, breast milk for younger children, or mashed potatoes or apple puree for older children to mask taste). Stir for 30 seconds and administer immediately. Administer lowest dose that effectively maintains liver function.

Patient/Family Teaching

• Instruct patient to take cholic acid as directed.
• Advise patient to take cholic acid 1 hr before or 4–6 hr after bile acid sequestrants or antacids containing aluminum.
• Inform patient of need for liver function tests. Caution patient to notify health care professional if signs and symptoms of worsening liver impairment (skin or whites of eyes turn yellow, urine turns dark or brown [tea colored], pain on the right side of stomach, bleeding or bruising occurs more easily than normal, or increased lethargy) occur.
• Rep:  Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage women who become pregnant during therapy to enroll in pregnancy registry (COCOA Registry [ChOlbam: Child and mOther's heAlth]) by calling 1-844-20C-OCOA or 1-844-202-6262 to enroll.

Evaluation/Desired Outcomes

Stable/improved hepatic parameters, ↑ weight, and improved survival.