Ofev Adverse Reactions

Summary of the safety profile: Clinical trials in adult patients: OFEV has been studied in clinical trials including 1,529 patients suffering from Idiopathic Pulmonary Fibrosis (IPF), 663 patients with other chronic fibrosing Interstitial Lung Diseases (ILDs) with a progressive phenotype, and 576 patients with Systemic Sclerosis associated Interstitial Lung Disease (SSc-ILD).
The safety data provided in the following are based on: Two Phase III, randomised, double-blind, placebo-controlled trials comparing treatment with OFEV 150 mg twice daily to placebo for 52 weeks (INPULSIS-1 and INPULSIS-2) in 1061 patients with IPF.
One phase III randomised, double-blind, placebo-controlled trial comparing treatment with OFEV 150 mg twice daily to placebo for at least 52 weeks in 663 patients with other chronic fibrosing ILDs with a progressive phenotype (INBUILD).
One phase III randomised, double-blind, placebo-controlled trial comparing treatment with OFEV 150 mg twice daily to placebo for at least 52 weeks in 576 patients with SSc-ILD (SENSCIS).
Data observed during the post-marketing experience.
In clinical trials, the most frequently reported adverse reactions associated with the use of OFEV included diarrhoea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
The safety profile of OFEV in a long term extension trial in patients with IPF, treated from 1 up to more than 5 years, was consistent with that observed in the phase III trials (see Pharmacology: Pharmacodynamics: Clinical Trials under Actions).
For the management of selected adverse reactions see Precautions.
Tabulated list of adverse reactions: The table as follows provides a summary of the adverse reactions by MedDRA System Organ Class (SOC) and frequency category.
Table 11 summarizes the frequencies of adverse drug reactions (ADRs) that were reported in the nintedanib group pooled from the two placebo-controlled Phase III INPULSIS trials of 52 weeks duration (638 patients with IPF), from the placebo-controlled phase III INBUILD trial (332 patients with other chronic fibrosing ILDs with a progressive phenotype), from the placebo-controlled Phase III SENSCIS trial (288 patients with SSc-ILD) or from the post-marketing period.
They are ranked under headings of System Organ Class and frequency using the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data). (See Table 11.)

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Description of selected adverse reactions: Diarrhoea: Diarrhoea was reported in 62.4% of patients treated with nintedanib. The event was reported to be of severe intensity in 3.3% of nintedanib treated patients. More than two thirds of patients experiencing diarrhoea reported its first onset already during the first three months of treatment. Diarrhoea led to permanent treatment discontinuation in 4.4% of patients; otherwise the events were managed by anti-diarrhoeal therapy, dose reduction or treatment interruption (see Precautions).
Hepatic enzyme increased: Liver enzyme elevations (see Precautions) were reported in 13.6% of nintedanib treated patients. Elevations of liver enzymes were reversible and not associated with clinically manifest liver disease. For further information about special populations, recommended measures and dosing adjustments in case of diarrhoea and hepatic enzyme increased, refer additionally to Precautions and Dosage & Administration, respectively.