Ofev Adverse Reactions

Summary of the safety profile: In clinical trials and during the post-marketing experience, the most frequently reported adverse reactions associated with the use of nintedanib included diarrhoea, nausea and vomiting, abdominal pain, decreased appetite, weight decreased and hepatic enzyme increased.
For the management of selected adverse reactions see Precautions.
Tabulated list of adverse reactions: Table 11 provides a summary of the adverse drug reactions (ADRs) by MedDRA System Organ Class (SOC) and frequency category 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: In clinical trials (see Pharmacology: Pharmacodynamics under Actions), diarrhoea was the most frequent gastro-intestinal event reported. In most patients, the event was of mild to moderate intensity. More than two thirds of patients experiencing diarrhoea reported its first onset already during the first three months of treatment. In most patients, the events were managed by anti-diarrhoeal therapy, dose reduction or treatment interruption (see Precautions). An overview of the reported diarrhoea events in the clinical trials is listed in Table 12. (See Table 12.)

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Hepatic enzyme increased: In the INPULSIS trials, liver enzyme elevations (see Precautions) were reported in 13.6% versus 2.6% of patients treated with Ofev and placebo, respectively. In the INBUILD trial, liver enzyme elevations were reported in 22.6% versus 5.7% of patients treated with Ofev and placebo, respectively. In the SENSCIS trial, liver enzyme elevations were reported in 13.2% versus 3.1% of patients treated with Ofev and placebo, respectively. 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.
Bleeding: In clinical trials, the frequency of patients who experienced bleeding was slightly higher in patients treated with Ofev or comparable between the treatment arms (Ofev 10.3% versus placebo 7.8% for INPULSIS; Ofev 11.1% versus placebo 12.7% for INBUILD; Ofev 11.1% versus placebo 8.3% for SENSCIS). Non-serious epistaxis was the most frequent bleeding event reported. Serious bleeding events occurred with low frequencies in the 2 treatment groups (Ofev 1.3% versus placebo 1.4% for INPULSIS; Ofev 0.9% versus placebo 1.5% for INBUILD; Ofev 1.4% versus placebo 0.7% for SENSCIS).
Post-marketing bleeding events include but are not limited to gastrointestinal, respiratory and central nervous organ systems, with the most frequent being gastrointestinal (see Precautions).
Proteinuria: In clinical trials, the frequency of patients who experienced proteinuria was low and comparable between the treatment arms (Ofev 0.8% versus placebo 0.5% for INPULSIS; Ofev 1.5% versus placebo 1.8% for INBUILD; Ofev 1.0% versus placebo 0.0% for SENSCIS). Nephrotic syndrome has not been reported in clinical trials. Very few cases of nephrotic range proteinuria with or without renal function impairment have been reported post-marketing. Histological findings in individual cases were consistent with glomerular microangiopathy with or without renal thrombi. Reversal of the symptoms has been observed after Ofev was discontinued, with residual proteinuria in some cases. Treatment interruption should be considered in patients who develop signs or symptoms of nephrotic syndrome (see Precautions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.