[Posted 09/21/2017]

AUDIENCE: Pharmacy, Hepatology, Gastroenterology

ISSUE: FDA is warning that the liver disease medicine Ocaliva (obeticholic acid) is being incorrectly dosed in some patients with moderate to severe decreases in liver function, resulting in an increased risk of serious liver injury and death. These patients are receiving excessive dosing, particularly a higher frequency of dosing than is recommended in the drug label for them. Ocaliva may also be associated with liver injury in some patients with mild disease who are receiving the correct dose. The recommended dosing and monitoring for patients on Ocaliva are described in the current drug label. FDA is working with the drug manufacturer, Intercept Pharmaceuticals, to address these safety concerns.

BACKGROUND: Ocaliva is used to treat a rare, chronic liver disease known as primary biliary cholangitis (PBC). PBC causes the bile ducts in the liver to become inflamed, damaged and destroyed. This causes bile, a fluid that helps in digestion, to build up in the liver. This build-up damages the liver over time, eventually causing it to lose its ability to function. Ocaliva has been shown to improve a certain blood test that measures liver problems.

RECOMMENDATIONS:

Health care professionals

• Determine the patient’s baseline liver function prior to starting Ocaliva.
• Patients with moderate to severe liver impairment (Child-Pugh B and C) should be started on the approved dosing schedule of 5 mg once weekly, rather than the 5 mg daily dosing used for other PBC patients, and if needed, can be increased up to a maximum approved dose of 10 mg twice weekly.
• Health care professionals should monitor patients frequently for disease progression, and reduce the dosing frequency to once- or twice-weekly for patients who progress to moderate or severe liver impairment.
• In all patients treated with Ocaliva, monitor frequently for liver injury (e.g., worsened liver blood tests and adverse liver-related reactions that may be inconsistent with the patient’s extent of disease). If liver injury is suspected, discontinue Ocaliva. After the patient has stabilized, weigh the benefits against the risks when deciding whether to re-initiate treatment.
• Educate patients on the symptoms of potential liver injury.

Patients

• Contact your health care professional if you have questions or concerns about taking Ocaliva.
• Report new or worsening severe skin itching to your health care professional.
• Contact your health care professional immediately if you develop any of the following symptoms that may be signs of liver injury:
  • New or worsening fatigue
  • Diarrhea
  • Weight loss
  • Abdominal pain
  • Decreased appetite
  • Nausea and vomiting
  • Change in behavior or confusion
  • Vague symptoms such as anxiety or unease
  • Abdominal swelling
  • Yellow eyes or skin
  • Bloody stools

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[09/21/2017 - Drug Safety Communication - FDA]