Reports of liver injuries stemming from the pulmonary fibrosis therapy Ofev (nintedanib), including a fatality, have prompted Health Canada to issue a safety warning about it to medical professionals.
The regulatory agency said 32 cases of Ofev-induced liver injuries due have been reported across the world since its approval in 2014. The majority have occurred in the first three months of treatment, and were resolved with lower doses of Ofev or discontinuation of the treatment.
Health Canada is working with Boehringer Ingelheim, Ofev’s manufacturer, to update the product’s label to warn that it can cause liver injuries. It is also working with the company on recommendations about when healthcare practitioners should check patients’ liver function.
Patients’ levels of transaminases (AST or ALT) and bilirubin, well-known biomarkers of liver function, should be checked just before patients start on Ofev, health officials said. This should be followed by monthly testing during the first three months of treatment, and periodically thereafter.
If transaminases levels reach three times the upper normal limit, the guidelines recommend a decrease in a patient’s Ofev dose or discontinuation of treatment. Signs or symptoms of liver damage — including yellowing of the skin or eyes, dark urine, abdominal pain, nausea, vomiting, or loss of appetite — should lead to the treatment being permanently discontinued, according to the guidelines.
Boehringer Ingelheim asks that cases of Ofev-induced adverse effects be brought to its attention with an email to PV_local_Canada@boehringer-ingelheim.com. Cases can be brought to Health Canada’s attention by calling 1-866-234-2345 or going to the Adverse Reaction Reporting webpage.
Ofev was designed to block the activity of several enzymes involved in the production of the protein collagen and its buildup in the lungs, fibroblast activation, and tissue scaring.
Several clinical trials have demonstrated that Ofev can benefit idiopathic pulmonary fibrosis patients by improving their lung function capacity, reducing their fibrosis scores, and impairing their disease progression.
The findings have been further supported by six-month treatment data collected from a Phase 3b trial (NCT01979952) involving 113 patients at 26 sites across the United States, Canada, and Turkey, and long-term effectiveness data from the global INPULSIS extension trials (NCT01335464 and NCT01335477), which included 734 IPF patients.