Obeticholic acid (Ocaliva▼): risk of serious liver injury in patients with pre-existing moderate or severe hepatic impairment; reminder to adjust dosing according to liver function monitoring

We are aware of reports of serious liver injuries and deaths in patients with primary biliary cholangitis with pre-existing moderate or severe liver impairment who were not adequately dose-adjusted. Follow dose reduction and monitoring advice in these patients to reduce the risk of serious liver injury.

Advice for healthcare professionals:

  • patients with pre-existing moderate or severe liver impairment who are taking obeticholic acid are at risk of serious liver injury; adequate dose reduction in these patients is therefore essential

  • assess hepatic status before starting obeticholic acid

  • start patients with Child-Pugh Class B or C or decompensated liver cirrhosis at a reduced dose of 5 mg once a week (rather than once a day) and only increase dosing frequency to 5 mg twice a week (at least 3 days apart) and subsequently 10 mg twice a week (at least 3 days apart) in these patients if an adequate reduction in alkaline phosphatase and/or total bilirubin has not been achieved after 3 months and if the patient is tolerating the medicine – see Summary of Product Characteristics

  • monitor all patients for primary biliary cholangitis (PBC) progression with laboratory and clinical assessment and evaluate at regular intervals the need for dose reduction

  • report any suspected adverse drug reactions to obeticholic acid via the Yellow Card Scheme

Background

Obeticholic acid (Ocaliva▼) is a farnesoid X receptor (FXR) agonist. It is indicated in the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA.

An EU review assessed reports of serious liver injuries and deaths in patients with primary biliary cholangitis with pre-existing moderate or severe liver impairment who were not adequately dose-adjusted. Liver-related adverse events have occurred both early in treatment and after months of treatment. Most cases were in the USA, but cases have also been reported in Europe.

The review concluded that no changes to the product information were required but suggested that healthcare professionals should be reminded of the dosing recommendations. A letter has also been sent to prescribers.

We have received 2 Yellow Card reports of hepatobiliary disorders in the UK associated with obeticholic acid. Neither case was fatal, but one case was life-threatening and required hospital admission and the other case led to discontinuation of therapy.

Hepatic status should be determined before starting treatment with obeticholic acid. Hepatically-impaired patients should receive a reduced starting dose of 5 mg once weekly in line with the recommendations in section 4.2 of the Summary of Product Characteristics for Ocaliva▼.

Call for reporting

Obeticholic acid (Ocaliva▼) is subject to additional monitoring, allowing quick identification of new safety information. Report any suspected adverse drug reactions to the Yellow Card Scheme.

Article citation: Drug Safety Update volume 11 issue 9; April 2018: 2.

Published 24 April 2018