For: Bile Acid Synthesis Disorders
Cholbam (cholic acid) is a bile acid preparation for the treatment of patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). CHOLBAM- cholic acid capsule
Manchester Pharmaceuticals
1 INDICATIONS AND USAGE
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) [see Clinical Trials (14.1)].
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 [see Clinical Trials (14.2)].
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.
2 DOSAGE AND ADMINISTRATION
2.1 Dosage Regimen for Bile Acid Synthesis Disorders due to Single Enzyme Defects and Peroxisomal Disorders 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.
DOSAGE FORMS AND STRENGTHS
CHOLBAM is available in two capsule strengths.
50 mg capsule: Size number 2 Swedish orange capsule with cap imprinted with "50mg" and body imprinted with "ASK001″. The capsules contain a white to off-white powder.
250 mg capsule: Size number 0 white capsule with a cap imprinted with "250mg" and body imprinted with "ASK002″. The capsules contain a white to off-white powder.
DESCRIPTION
Cholic acid is a bile acid produced by the liver where it is synthesized from cholesterol. The chemical formula is C24 H40 O5 , the molecular weight is 408.57 and the chemical structure is:
Chemical Structure
(click image for full-size original)
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 silicified microcrystalline cellulose, magnesium stearate and hard gelatin capsules. The size 2 shells contain gelatin, red iron oxide and titanium dioxide and the size 0 shells contain gelatin and titanium dioxide. CHOLBAM is administered orally.
12 CLINICAL PHARMACOLOGY
12.1 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 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.