Overview
11 DESCRIPTION CTEXLI (chenodiol) is a bile acid. Chenodiol is a bitter-tasting, white powder consisting of crystalline and amorphous particles that are freely soluble in methanol, acetone and acetic acid, and practically insoluble in water. The chemical name of chenodiol is 3α,7α-dihydroxy-5-β-cholan-24-oic acid. The molecular formula is C 24 H 40 O 4 and the molecular weight is 392.58 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Endogenous chenodiol (chenodeoxycholic acid) is a primary bile acid, synthesized from cholesterol in the liver. In CTX, the major bile acid synthesis pathways are disrupted due to partial or total deficiency in sterol 27-hydroxylase encoded by the CYP27A1 gene. CTEXLI may act to replace deficient levels of the endogenous bile acid chenodeoxycholic acid in patients with CTX. Increased chenodiol levels in the enterohepatic bile acid pool restore the activation of farnesoid X receptor (FXR) and downregulate CYP7A1 leading to suppression and reduction of atypical bile acids and bile alcohols including cholestanol and 23S-pentol. 12.
Indications
- 1 INDICATIONS AND USAGE CTEXLI is indicated for the treatment of cerebrotendinous xanthomatosis (CTX) in adults. CTEXLI is a bile acid indicated for treatment of cerebrotendinous xanthomatosis (CTX) in adults. ( 1 )
Common Doses
- 250 mg
Dosage
2 DOSAGE AND ADMINISTRATION • Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients. ( 2.1 ) • The recommended dosage is 250 mg orally three times daily. ( 2.2 ) 2.1 Important Recommendation Prior to CTEXLI Treatment Initiation Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients [see Warnings and Precautions ( 5.1 )] . 2.
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in the labeling: • Hepatotoxicity [see Warnings and Precautions ( 5.1 )] The most common adverse reactions (incidence > 14%) are diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mirum Pharmaceuticals at 1-855-MRM-4YOU or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS • Bile acid sequestering agents and aluminum-based antacids: Avoid concomitant use with CTEXLI. ( 7.1 ) • Coumarin and its derivatives: Monitor prothrombin time and adjust dosage accordingly. ( 7.2 ) 7.1 Effect of Other Drugs on CTEXLI Co-administration of bile acid sequestering agents, such as cholestyramine and colestipol, or aluminum-based antacids may decrease absorption of CTEXLI in the intestine and may result in decreased efficacy of CTEXLI. Avoid concomitant use of bile acid sequestering agents or aluminum-based antacids with CTEXLI. 7.