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Cholic Acid

FDA Drug Information • Also known as: Cholbam

Brand Names
Cholbam
Dosage Form
POWDER
Product Type
BULK INGREDIENT

Description

11 DESCRIPTION Cholic acid is a bile acid. The chemical formula is C 24 H 40 O 5 , the molecular weight is 408.57 and the chemical structure is: Cholic acid is a white to off-white powder. It is practically insoluble in water and in 0.1 M HCl at 20°C and is sparingly soluble in 0.1 M NaOH at 20°C. It is soluble in glacial acetic acid, alcohols, and acetone. A saturated solution in water at 20°C has a pH of 4.4. CHOLBAM capsules contain 50 mg or 250 mg of cholic acid as the active ingredient in size 2 Swedish orange or size 0 white opaque gelatin capsules, respectively. Inactive ingredients in CHOLBAM include crospovidone, magnesium stearate, and silicified microcrystalline cellulose. The size 2 capsule shells contain gelatin, red iron oxide and titanium dioxide, and the size 0 capsule shells contain gelatin and titanium dioxide. CHOLBAM is administered orally. Chemical Structure

What Is Cholic Acid Used For?

1 INDICATIONS AND USAGE CHOLBAM is a bile acid indicated for: Treatment of bile acid synthesis disorders due to single enzyme defects (SEDs). ( 1.1 ) 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. ( 1.2 ) Limitations of use: The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established. ( 1.3 ). 1.1 Bile Acid Synthesis Disorders due to Single Enzyme Defects CHOLBAM is indicated for the treatment of bile acid synthesis disorders due to single enzyme defects (SEDs) 1.2 Peroxisomal Disorders Including Zellweger Spectrum Disorders CHOLBAM is 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. 1.3 Limitation of Use The safety and effectiveness of CHOLBAM on extrahepatic manifestations of bile acid synthesis disorders due to SEDs or PDs including Zellweger spectrum disorders have not been established.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dosage is 10 to 15 mg/kg once daily or in two divided doses, in pediatric patients and adults. See prescribing information for weight-based dosing tables. ( 2.1 ) The recommended dosage in patients with concomitant familial hypertriglyceridemia is 11 to 17 mg/kg once daily or in two divided doses and is adjusted based on clinical response ( 2.1 ) 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 next three years and annually thereafter. Administer the lowest dose that effectively maintains liver function. ( 2.2 ) Discontinue CHOLBAM if liver 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 liver function or cholestasis; continue to monitor liver function and consider restarting at a lower dose when parameters return to baseline. ( 2.2 , 5.1 ) Administration Instructions: Take with food. ( 2.3 ) Do not crush or chew the capsules. For patients unable to swallow the capsules, the capsules can be opened and the contents mixed with drink/food ( 2.3 ) 2.1 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. Table 1: Number of CHOLBAM Capsules Needed to Achieve a Recommended Dosage of 10 mg/kg/day 10 mg/kg/day Dosage Body Weight (kg) Number of 50 mg capsules Number of 250 mg capsules 4 to 6 1 0 7 to 10 2 0 11 to 15 3 0 16 to 20 4 0 21 to 25 0 1 26 to 30 1 1 31 to 35 2 1 36 to 40 3 1 41 to 45 4 1 46 to 50 0 2 51 to 55 1 2 56 to 60 2 2 61 to 65 3 2 66 to 70 4 2 71 to 75 0 3 76 to 80 1 3 Table 2: Number of CHOLBAM Capsules Needed to Achieve a Recommended Dosage of 15 mg/kg/day 15 mg/kg/day Dosage Body Weight (kg) Number of 50 mg capsules Number of 250 mg capsules 4 to 5 1 0 6 to 9 2 0 10 to 13 3 0 14 to 16 4 0 17 to 19 0 1 20 to 23 1 1 24 to 26 2 1 27 to 29 3 1 30 to 33 4 1 34 to 36 0 2 37 to 39 1 2 40 to 43 2 2 44 to 46 3 2 47 to 49 4 2 50 to 53 0 3 54 to 56 1 3 57 to 59 2 3 60 to 63 3 3 64 to 66 4 3 67 to 69 0 4 70 to 73 1 4 74 to 76 2 4 77 to 79 3 4 80 4 4 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in the labeling: Exacerbation of Liver Impairment [see Warnings and Precautions (5.1) ] Most common adverse reactions (≥1%) are diarrhea, reflux esophagitis, malaise, jaundice, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Travere Therapeutics, Inc. at 1-877-659-5518 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clinical safety experience with CHOLBAM consists of: Trial 1: a non-randomized, open-label, single-arm trial of 50 patients with bile acid synthesis disorders due to SEDs and 29 patients with PDs including Zellweger spectrum disorders. Safety data are available over the 18 years of the trial. Trial 2: an extension trial of 12 new patients (10 SED and 2 PD) along with 31 (21 SED and 10 PD) patients who rolled over from Trial 1. Safety data are available for 3 years and 11 months of treatment. Adverse events were not collected systematically in either of these trials. Most patients received an oral dose of 10 to 15 mg/kg/day of CHOLBAM. Deaths In Trial 1, among the 50 patients with SEDs, 5 patients aged 1 year or less died, which included three patients originally diagnosed with AKR1D1 deficiency, one with 3β-HSD deficiency and one with CYP7A1 deficiency. The cause of death was attributed to progression of underlying liver disease in every patient. Of the 29 patients in Trial 1 with PDs including Zellweger spectrum disorders, 12 patients between the ages of 7 months and 2.5 years died. In the majority of these patients (8/12), the cause of death was attributed to progression of underlying liver disease or to a worsening of their primary illness. Two additional patients in Trial 1 (1 SED and 1 PD) died who had been off study medication for more than one year with the cause of death most likely being a progression of their underlying liver disease. Of the patients who died with disease progression, laboratory testing showed abnormal serum transaminases, bilirubin, or cholestasis on liver biopsy suggesting worsening of their underlying cholestasis. In Trial 2, among the 31 patients with SED, two patients (1 new patient and 1 who rolled over from Trial 1) died. The cause of death in both cases was unrelated to their primary treatment or progression of their underlying liver disease. Of the 12 patients with PD in Trial 2, four patients died between the ages of 4 and 8 years (1 new patient and 3 who rolled over from Trial 1). The cause of death in three of these patients was attributed to progression of underlying liver disease or to a worsening of their primary illness. Worsening Liver Impairment Seven patients in Trial 1(4 SED and 3 PD) and 3 patients in Trial 2 (1 SED and 2 PD) experienced worsening serum transaminases, elevated bilirubin values, or worsening cholestasis on liver biopsy during treatment [see Warnings and Precautions (5.1) ] . Common Adverse Reactions There were 12 adverse reactions reported across 9 patients in the trials, with diarrhea being the most common reaction in approximately 2% of the patient population. All other adverse reactions represented 1% of the patient population. The breakdown by trial follows: Table 3: Most Common Adverse Reactions in Trials 1 and 2 Adverse Reactions Trial 1 Trial 2 Adverse reactions that occurred in new patients Overall n (%) Diarrhea 1 2 3 (2) Reflux Esophagitis 1 0 1 (1) Malaise 1 0 1 (1) Jaundice 1 0 1 (1) Skin lesion 1 0 1 (1) Nausea 0 1 1 (1) Abdominal Pain 0 1 1 (1) Intestinal Polyp 0 1 1 (1) Urinary Tract Infection 0 1 1 (1) Peripheral Neuropathy 0 1 1 (1)...

Drug Interactions

7 DRUG INTERACTIONS Bile Salt Efflux Pump (BSEP) Inhibitors (e.g., cyclosporine) : Avoid concomitant use; if concomitant use is necessary, monitor serum transaminases and bilirubin ( 7.1 ) Bile Acid Resins and Aluminum-Based Antacids: 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 antacids. ( 2.3 , 7.1 ) 7.1 Effects of other drugs on CHOLBAM Drug interactions with CHOLBAM mainly relate to agents capable of interrupting the enterohepatic circulation of bile acids. Inhibitors of Bile Acid Transporters Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended. Bile Acid Binding Resins Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of CHOLBAM. 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 [see Dosage and Administration (2.3) ] . Aluminum-Based Antacids Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of CHOLBAM. Take CHOLBAM at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid [see Dosage and Administration (2.3) ] .

Contraindications

4 CONTRAINDICATIONS None. None ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy surveillance program that monitors pregnancy outcomes in women exposed to CHOLBAM during pregnancy [COCOA Registry (ChOlbam: Child and mOther's heAlth)]. Women who become pregnant during CHOLBAM treatment are encouraged to enroll. Patients or their health care provider should call 1-844-20C-OCOA or 1-844-202-6262 to enroll. Risk Summary No studies in pregnant women or animal reproduction studies have been conducted with CHOLBAM. Limited published case reports discuss pregnancies in women taking cholic acid for 3β-HSD deficiency resulting in healthy infants. These reports may not adequately inform the presence or absence of drug-associated risk with the use of CHOLBAM during pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Overdosage

10 OVERDOSAGE Concurrent elevations of serum GGT and ALT may indicate CHOLBAM overdose. If an overdose is suspected, discontinue CHOLBAM and treat symptoms. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 50 mg Capsules CHOLBAM capsules are available as two-piece gelatin capsules with a Swedish orange cap imprinted with "50mg" and Swedish orange body imprinted with "ASK001". The capsules contain a white or off-white powder and are supplied in bottles of: 90 capsules (NDC 45043-001-02) 250 mg Capsules CHOLBAM capsules are available as two-piece gelatin capsules with a white cap imprinted with "250mg" and white body imprinted with "ASK002". The capsules contain a white or off-white powder and are supplied in bottles of: 90 capsules (NDC 45043-002-02) Storage and Handling Store at 20°C–25°C (69°F-77°F), excursions permitted between 15°C-30°C (59°F-86°F). [see USP Controlled Room Temperature].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.