Canadian Health Officials Issue Safety Warning on Ofev After Liver Injury Cases

Health Canada has issued a safety warning on Boehringer Ingelheim’s idiopathic pulmonary fibrosis therapy Ofev (nintedanib) after patients in a number of countries developed liver injuries and one died.

IPF patients should stop taking Ofev and seek medical assistance if they develop signs of liver damage, Canadian officials said. Those signs included yellowing of the skin or eyes, dark urine, abdominal pain, nausea, vomiting, or loss of appetite.

Health officials had recorded 32 cases of Ofev-induced liver injury worldwide through October 2017, including one in Canada. The outcomes are known for 24 out of the 32 cases.

Reducing the dose of Ofev or stopping it completely resolved the liver damage in 17 cases. But six patients have failed to recover, and one died.

Health Canada has advised healthcare professionals to closely monitor patients being treated with Ofev for markers of liver damage, including liver transaminases and bilirubin levels.

Monitoring should start just before patients begin treatment, followed by monthly measurements during the first three months, and then periodically — at each patient visit, for example. Most of the liver damage cases occurred within three months of patients starting treatment, so doctors should be especially diligent in monitoring during this period, officials said.

Health Canada has warned all medical personnel that if a patient’s transaminase levels — both alanine aminotransferase and aspartate transaminase — become triple the upper normal level, they should reduce their Ofev dose.

If the increased levels correlate with signs or symptoms of liver injury, such as jaundice, patients must stop taking Ofev.

This new information is available to healthcare professionals and patients at the Recalls and Safety Alerts Database on the Healthy Canadians website. It is also being disseminated through the MedEffect e-Notice email notification system.

Health Canada is working with Boehringer Ingelheim to update the Canadian Product Monograph with the new safety instructions for Ofev.

The U.S. Food and Drug Administration approved Ofev as a therapy for idiopathic pulmonary fibrosis in October 2014. The European Commission granted approval in January 2015.

Ofev’s approvals were based on clinical trial results. The most decisive came from the Phase 3 INPULSIS studies (NCT01335464 and NCT01335477), showing that Ofev slows the progression of pulmonary fibrosis regardless of the patient’s disease stage.

Boehringer Ingelheim recommends that patients take one 150-mg capsule of Ofev twice a day.