This Relatively New Idiopathic Pulmonary Fibrosis (IPF) Pill Is Clearly On The Radar Of Drug Safety Regulators
OFEV (nintedanib) capsules were approved by the FDA in 2014 for treatment of idiopathic pulmonary fibrosis (IPF). Boehringer Ingelheim Pharmaceuticals, Inc. is the drug company responsible for OFEV in the US.
On January 11, 2018 Health Canada issued a Dear Healthcare Professional Letter communication titled "OFEV (nintedanib) - Risk of Drug-Induced Liver Injury and the Need for Regular Monitoring of Liver Function".
From the Background Information section of that new Health Canada document we get this overview of the safety issue:
OFEV (nintedanib) is used to treat idiopathic pulmonary fibrosis (IPF).
Cases of [drug-induced liver injury (DILI)] have been observed with OFEV treatment in the post-marketing setting since the product was launched in 2014. The overall cumulative [idiopathic pulmonary fibrosis (IPF)] patient exposure to OFEV from marketing experience is estimated to be over 32,000 patient-years. As of October 15, 2017, 32 cases of DILI have been reported worldwide in patients treated with OFEV, including one in Canada. In 24 of the 32 cases, the outcome of the DILI events was reported. In the majority (17) of these cases, the DILI event resolved when the dose was reduced or treatment was stopped. In 6 cases, the patient had not recovered at the time of reporting. One case resulted in fatal outcome.
That document went on to state "Health Canada is working with the manufacturer to update the Canadian Product Monograph [for OFEV] with this safety information."
Strictly Confidential, No Obligation.
This forthcoming label change for OFEV in Canada follows similar regulatory action taken in the US several months ago, as indicated by an August 4, 2017 letter from the FDA to Boehringer Ingelheim Pharmaceuticals Inc.
As regards the OFEV - liver drug safety issue, the following text was added to the Warnings and Precautions part of the Full Prescribing Information for OFEV document (accessed 1/11/18) as a result of that August 2017 FDA letter:
5.2 Elevated Liver Enzymes
Cases of drug-induced liver injury have been observed with OFEV treatment [see Adverse Reactions (6.2)]. In the post-marketing period, non-serious and serious cases of drug-induced liver injury, including severe liver injury with fatal outcome, have been reported. The majority of hepatic events occur within the first three months of treatment. In clinical trials, administration of OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, GGT) and bilirubin. Liver enzyme and bilirubin increases were reversible with dose modification or interruption in the majority of cases. The majority (94%) of patients with ALT and/or AST elevations had elevations <5 times ULN. The majority (95%) of patients with bilirubin elevations had elevations <2 times ULN [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]. Patients with a low body weight (<65 kg), Asian, and female patients may have a higher risk of elevations in liver enzymes. Nintedanib exposure increased with patient age, which may also result in a higher risk of increased liver enzymes [see Clinical Pharmacology (12.3)]. Conduct liver function tests (ALT, AST, and bilirubin) upon initiation of treatment with OFEV, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Dosage modifications or interruption may be necessary for liver enzyme elevations. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with OFEV, promptly interrupt therapy [see Dosage and Administration (2.1, 2.3)].
We will continue monitor the medical literature, FDA, and Health Canada for further developments regarding this drug-induced liver injury issue for OLEV.
DrugInjuryLaw.com: Medical & Legal Information About Drug Side Effects (All website content by attorney Tom Lamb)
Drug Injury Case Evaluation - Free. Confidential. No Obligation. (Case review done by attorney Tom Lamb)