Cerebrotendinous Xanthomatosis page loaded

Cerebrotendinous Xanthomatosis (CTX)

Clinical Presentation: Learn about mutations in CYP27A1 as part of the mechanism of disease for CTX, the hallmark manifestations of CTX (chronic diarrhea, cataracts, xanthomas, and neurological deterioration), and related laboratory assessments.1-3

Topics Include

  • •Hallmark Clinical Presentation of CTX
  • •CYP27A1 Mutations in CTX Mechanism of Disease
  • •Laboratory Assessments for CTX

Speaker Information

  • •
    Robert D. Steiner, MD, FAAP, FACMG
    University of Wisconsin, School of Medicine and Public Health
  • •
    Ernst J. Schaefer, MD, FNLA, FAHA
    Tufts University School of Medicine, Department of Medicine

Acronyms: CTX: cerebrotendinous xanthomatosis; CYP27A1: cytochrome P450 family 27 subfamily A member 1.

References: 1. Sekijima Y, et al. J Hum Genet. 2018;63(3):271-280. 2. Mignarri A, et al. J Inherit Metab Dis. 2014;37(3):421-429. 3. Mignarri A, et al. J Inherit Metab Dis. 2016;39:75-83.

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Chenodiol, including CTEXLI, has been associated with hepatotoxicity. Patients with preexisting liver disease or bile duct abnormalities may be at a higher risk for hepatotoxicity during treatment.

Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients. Monitor liver transaminase (ALT, AST) and total bilirubin levels yearly and as clinically indicated. If liver transaminase levels are elevated >3 times the upper limit of normal (ULN) or total bilirubin level is >2 times ULN, interrupt treatment until the levels have returned to baseline values. For persistent or recurrent liver test abnormalities, consider discontinuing CTEXLI.

Inform the patient of the symptoms of hepatotoxicity (e.g., abdominal pain, bruising, dark-colored urine, fatigue, bleeding, jaundice, nausea, and pruritus). Have the patient discontinue CTEXLI immediately if clinical signs and symptoms consistent with hepatotoxicity occur.

ADVERSE REACTIONS

The most common adverse reactions (≥14%) during CTEXLI treatment were diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection.

DRUG INTERACTIONS

Bile acid sequestering agents and aluminum-based antacids: Avoid concomitant use with 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.

Coumarin and its derivatives: Monitor prothrombin time and adjust the dosage of coumarin or its derivatives if concomitant use with CTEXLI is unavoidable. Due to potential hepatotoxicity, CTEXLI may affect the pharmacodynamics of coumarin and its derivatives, causing unexpected prolongation of the prothrombin time and hemorrhage.

DOSING AND ADMINISTRATION

The recommended dosage of CTEXLI is 250 mg administered orally three times daily, with or without food. Swallow tablets whole.

Please see accompanying full Prescribing Information.

WARNINGS AND PRECAUTIONS

Hepatotoxicity: Chenodiol, including CTEXLI, has been associated with hepatotoxicity. Patients with preexisting liver disease or bile duct abnormalities may be at a higher risk for hepatotoxicity during treatment.

Before initiating CTEXLI, obtain baseline liver transaminase (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and total bilirubin levels in all patients. Monitor liver transaminase (ALT, AST) and total bilirubin levels yearly and as clinically indicated. If liver transaminase levels are elevated >3 times the upper limit of normal (ULN) or total bilirubin level is >2 times ULN, interrupt treatment until the levels have returned to baseline values. For persistent or recurrent liver test abnormalities, consider discontinuing CTEXLI.

Inform the patient of the symptoms of hepatotoxicity (e.g., abdominal pain, bruising, dark-colored urine, fatigue, bleeding, jaundice, nausea, and pruritus). Have the patient discontinue CTEXLI immediately if clinical signs and symptoms consistent with hepatotoxicity occur.

ADVERSE REACTIONS

The most common adverse reactions (≥14%) during CTEXLI treatment were diarrhea, headache, abdominal pain, constipation, hypertension, muscular weakness, and upper respiratory tract infection.

DRUG INTERACTIONS

Bile acid sequestering agents and aluminum-based antacids: Avoid concomitant use with 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.

Coumarin and its derivatives: Monitor prothrombin time and adjust the dosage of coumarin or its derivatives if concomitant use with CTEXLI is unavoidable. Due to potential hepatotoxicity, CTEXLI may affect the pharmacodynamics of coumarin and its derivatives, causing unexpected prolongation of the prothrombin time and hemorrhage.

DOSING AND ADMINISTRATION

The recommended dosage of CTEXLI is 250 mg administered orally three times daily, with or without food. Swallow tablets whole.

Please see accompanying full Prescribing Information.