Nintedanib side effects: what 31,130 FDA adverse event reports show
Drug class
Kinase inhibitor
Who reports
31,130 reports · 68% serious · 6,187 with death outcome · 42% female
Used for
Nintedanib is a kinase inhibitor indicated in adults for: Treatment of idiopathic pulmonary fibrosis (IPF). ( 1.1 ) Treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype. ( 1.2 ) Slowing the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD).
What it is
Nintedanib capsules contain nintedanib, a kinase inhibitor [see Mechanism of Action ( 12.1 )]. Nintedanib is presented as the ethanesulfonate salt (esylate), with the chemical name 1 H -Indole.
Boxed warning
None in the current label
Causality screen of the 40 strongest signals
What the badges mean
- Labeled (related wording) The label describes this effect under different wording (e.g. 'neutropenia' for 'neutrophil count decreased'). Treated as known.
- Likely indication confounding The term appears in the label's indications: reports probably describe the disease being treated (or its progression), not a drug effect. Classic confounding by indication.
- Reporting / coding artifact An administrative, monitoring or exposure term (product issue, off-label use, 'test normal', overdose...). Not a biological reaction; a high PRR here reflects how reports are coded.
- Lab value / disease marker A laboratory result, investigation or disease-activity marker (antibody positive, CRP abnormal, swollen joint count) not described in the label. These usually mirror the monitored disease or testing protocol rather than a drug effect; not screened further.
- Not in label — unassessed Not found in the label text, not an artifact pattern. This is a genuine candidate for a formal causality assessment (Bradford Hill / WHO-UMC); it has NOT had one here.
Strongest disproportionality signals
Flagged terms (PRR ≥ 2, χ² ≥ 4, n ≥ 10), ranked by PRR; infinite PRRs (no comparator reports) excluded. The EBGM column is a second, shrinkage-based estimate (MGPS) with its 5th percentile EB05 and the BCPNN IC025; a pair flagged by PRR alone is marked PRR-only and should be read as fragile. The strata column recomputes the PRR on serious reports only (and, for the 300 most-reported drugs, adjusted for age band), and flags pairs whose reports are unusually skewed by sex or come mostly from consumers. Each row also shows the PRR against the other drugs of the same FDA class, which removes most confounding by the condition being treated, and a calibrated p-value: on validation, known non-causes average an ROR of about 2, so significance is judged against that empirical null (✓ = p < 0.05 after calibration). 1,071 further terms are in the interactive explorer. Reaction links open the term's cross-drug page.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Idiopathic pulmonary fibrosis | 2,111 | 812.9 763.5–865.5ROR 871.9 · calibrated p 1e-16 ✓ | 364.4 EB05 351.6 · IC025 +8.3 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=2,088 | NCT02607722: 1000/5,734 (17.4%) on Nintedanib (serious AE) |
| Connective tissue disease-associated interstitial lung disease | 13 | 232.8 123.8–438.0ROR 232.9 · calibrated p 3e-9 ✓ | 138.1 EB05 85.9 · IC025 +3.6 3/3 methods agree | Labeled (related wording) related wording | serious n=13 | not reported in cached trials |
| Systemic sclerosis pulmonary | 12 | 194.0 101.9–369.0ROR 194.0 · calibrated p 1e-8 ✓ | 121.7 EB05 74.2 · IC025 +3.5 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=11 | not reported in cached trials |
| Lung diffusion test decreased | 64 | 129.7 99.2–169.5ROR 130.0 · calibrated p 3e-8 ✓ | 105.3 EB05 85.4 · IC025 +5.5 3/3 methods agree | Not in label — unassessed | serious n=60 | not reported in cached trials |
| Forced vital capacity decreased | 99 | 121.3 97.9–150.2ROR 121.7 · calibrated p 3e-8 ✓ | 100.7 EB05 85.1 · IC025 +5.8 3/3 methods agree | Not in label — unassessed | serious n=92 | not reported in cached trials |
| Cough decreased | 17 | 97.1 58.4–161.6ROR 97.2 · calibrated p 7e-7 ✓ | 77.7 EB05 51.4 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | – | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Kl-6 increased | 25 | 89.1 58.7–135.2ROR 89.1 · calibrated p 8e-7 ✓ | 74.3 EB05 53.0 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=25 | NCT02607722: 1/5,734 (0.0%) on Nintedanib (serious AE) |
| Bendopnoea | 22 | 79.7 51.2–124.0ROR 79.7 · calibrated p 2e-6 ✓ | 67.3 EB05 46.8 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious n=14 · 100% consumer | not reported in cached trials |
| Oxygen saturation increased | 33 | 71.7 50.1–102.7ROR 71.8 · calibrated p 3e-6 ✓ | 62.6 EB05 46.6 · IC025 +4.5 3/3 methods agree | Lab value / disease marker | serious n=30 · 100% consumer | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Oxygen consumption | 15 | 68.1 40.0–115.8ROR 68.1 · calibrated p 8e-6 ✓ | 57.6 EB05 37.0 · IC025 +3.5 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Post-tussive vomiting | 13 | 61.1 34.6–107.8ROR 61.1 · calibrated p 2e-5 ✓ | 52.0 EB05 32.3 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | – | not reported in cached trials |
| Oxygen consumption increased | 172 | 52.8 45.2–61.7ROR 53.1 · calibrated p 1e-5 ✓ | 48.7 EB05 42.9 · IC025 +5.2 3/3 methods agree | Lab value / disease marker | serious n=125 · 85% consumer | not reported in cached trials |
| Lung transplant | 234 | 47.2 41.4–53.9ROR 47.6 · calibrated p 2e-5 ✓ | 44.0 EB05 39.5 · IC025 +5.1 3/3 methods agree | Not in label — unassessed | serious n=226 | NCT02607722: 4/5,734 (0.1%) on Nintedanib (serious AE) |
| Systemic scleroderma | 45 | 44.8 33.2–60.6ROR 44.9 · calibrated p 4e-5 ✓ | 41.4 EB05 32.2 · IC025 +4.4 3/3 methods agree | Likely indication confounding shares a disease stem with the indications wording | serious n=45 · ♀ 72% (drug 42%) | not reported in cached trials |
| Total lung capacity abnormal | 22 | 41.2 26.8–63.3ROR 41.2 · calibrated p 9e-5 ✓ | 37.7 EB05 26.2 · IC025 +3.7 3/3 methods agree | Not in label — unassessed | serious n=22 | not reported in cached trials |
| Dairy intolerance | 16 | 40.6 24.5–67.3ROR 40.6 · calibrated p 1e-4 ✓ | 36.8 EB05 24.0 · IC025 +3.3 3/3 methods agree | Not in label — unassessed | serious n=12 | not reported in cached trials |
| Walking distance test abnormal | 21 | 38.7 24.9–60.0ROR 38.7 · calibrated p 1e-4 ✓ | 35.5 EB05 24.5 · IC025 +3.6 3/3 methods agree | Reporting / coding artifact | serious n=14 | not reported in cached trials |
| Pulmonary function test abnormal | 79 | 35.8 28.5–44.9ROR 35.9 · calibrated p 1e-4 ✓ | 33.8 EB05 28.0 · IC025 +4.4 3/3 methods agree | Reporting / coding artifact | serious n=70 · 75% consumer | not reported in cached trials |
| Idiopathic interstitial pneumonia | 17 | 34.9 21.4–56.8ROR 34.9 · calibrated p 3e-4 ✓ | 32.1 EB05 21.2 · IC025 +3.3 3/3 methods agree | Labeled (related wording) related wording | serious n=15 | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Total lung capacity decreased | 79 | 34.9 27.8–43.7ROR 34.9 · calibrated p 1e-4 ✓ | 32.9 EB05 27.3 · IC025 +4.4 3/3 methods agree | Not in label — unassessed | serious n=59 · 78% consumer | not reported in cached trials |
| Diverticulitis intestinal haemorrhagic | 19 | 34.5 21.8–54.7ROR 34.5 · calibrated p 3e-4 ✓ | 31.9 EB05 21.6 · IC025 +3.4 3/3 methods agree | Not in label — unassessed | serious n=19 | not reported in cached trials |
| Pulmonary function test decreased | 212 | 34.0 29.6–39.0ROR 34.2 · calibrated p 1e-4 ✓ | 32.3 EB05 28.8 · IC025 +4.7 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=182 | not reported in cached trials |
| Chronic respiratory failure | 57 | 33.8 25.9–44.1ROR 33.8 · calibrated p 2e-4 ✓ | 31.9 EB05 25.5 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=54 | NCT02607722: 13/5,734 (0.2%) on Nintedanib (serious AE) |
| Hypersensitivity pneumonitis | 54 | 33.7 25.6–44.2ROR 33.7 · calibrated p 2e-4 ✓ | 31.8 EB05 25.3 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious n=54 | NCT02607722: 1/5,734 (0.0%) on Nintedanib (serious AE) |
| Faeces soft | 311 | 30.2 26.9–33.8ROR 30.5 · calibrated p 3e-4 ✓ | 28.9 EB05 26.3 · IC025 +4.6 3/3 methods agree | Not in label — unassessed | serious n=253 · 77% consumer | not reported in cached trials |
| Oxygen consumption decreased | 24 | 27.6 18.3–41.5ROR 27.6 · calibrated p 7e-4 ✓ | 26.0 EB05 18.4 · IC025 +3.4 3/3 methods agree | Lab value / disease marker | serious n=18 · 79% consumer | not reported in cached trials |
| Abnormal loss of weight | 240 | 24.7 21.7–28.1ROR 24.9 · calibrated p 7e-4 ✓ | 23.8 EB05 21.4 · IC025 +4.3 3/3 methods agree | Not in label — unassessed | serious n=72 | not reported in cached trials |
| Increased viscosity of bronchial secretion | 21 | 23.1 14.9–35.7ROR 23.1 · calibrated p 0.002 ✓ | 21.9 EB05 15.1 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=16 | not reported in cached trials |
| Oxygen saturation abnormal | 89 | 22.0 17.9–27.2ROR 22.1 · calibrated p 0.001 ✓ | 21.3 EB05 17.8 · IC025 +3.9 3/3 methods agree | Lab value / disease marker | serious n=73 · 80% consumer | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Sputum increased | 65 | 21.3 16.6–27.3ROR 21.3 · calibrated p 0.002 ✓ | 20.6 EB05 16.7 · IC025 +3.8 3/3 methods agree | Not in label — unassessed | serious n=49 · 83% consumer | not reported in cached trials |
| Pulmonary fibrosis | 571 | 20.7 19.0–22.5ROR 21.1 · calibrated p 0.002 ✓ | 20.1 EB05 18.7 · IC025 +4.2 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious PRR 16.9 | NCT02607722: 1000/5,734 (17.4%) on Nintedanib (serious AE) |
| Dyspnoea exertional | 1,117 | 20.6 19.4–21.8ROR 21.3 · calibrated p 0.001 ✓ | 20.0 EB05 19.0 · IC025 +4.2 3/3 methods agree | Not in label — unassessed | serious PRR 16.9 · 79% consumer | NCT02607722: 8/5,734 (0.1%) on Nintedanib (serious AE) |
| Dependence on oxygen therapy | 14 | 20.2 11.9–34.3ROR 20.2 · calibrated p 0.004 ✓ | 18.9 EB05 11.6 · IC025 +2.7 3/3 methods agree | Reporting / coding artifact | serious n=13 | not reported in cached trials |
| Pneumomediastinum | 52 | 20.2 15.3–26.6ROR 20.2 · calibrated p 0.002 ✓ | 19.5 EB05 15.4 · IC025 +3.6 3/3 methods agree | Not in label — unassessed | serious n=51 · 100% clinician | NCT02607722: 41/5,734 (0.7%) on Nintedanib (serious AE) |
| Telangiectasia | 27 | 19.6 13.4–28.7ROR 19.6 · calibrated p 0.003 ✓ | 18.8 EB05 13.5 · IC025 +3.2 3/3 methods agree | Not in label — unassessed | serious n=27 · ♀ 100% (drug 42%) | not reported in cached trials |
| Pneumothorax spontaneous | 19 | 19.3 12.2–30.4ROR 19.3 · calibrated p 0.004 ✓ | 18.3 EB05 12.2 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious n=19 | NCT02607722: 15/5,734 (0.3%) on Nintedanib (serious AE) |
| Clubbing | 11 | 18.5 10.2–33.7ROR 18.5 · calibrated p 0.006 ✓ | 16.9 EB05 9.1 · IC025 +2.3 3/3 methods agree | Not in label — unassessed | serious n=9 | not reported in cached trials |
| Productive cough (cough with phlegm) | 1,262 | 18.4 17.4–19.4ROR 19.1 · calibrated p 0.002 ✓ | 17.9 EB05 17.1 · IC025 +4.1 3/3 methods agree | Not in label — unassessed | serious PRR 17.8 · 83% consumer | NCT02607722: 1/5,734 (0.0%) on Nintedanib (serious AE) |
| Dizziness exertional | 19 | 17.6 11.2–27.8ROR 17.6 · calibrated p 0.005 ✓ | 16.7 EB05 11.0 · IC025 +2.8 3/3 methods agree | Not in label — unassessed | serious n=10 | not reported in cached trials |
| Sputum retention | 21 | 14.7 9.6–22.7ROR 14.8 · calibrated p 0.010 ✓ | 13.9 EB05 9.2 · IC025 +2.7 3/3 methods agree | Not in label — unassessed | serious n=21 | not reported in cached trials |
Trial evidence (ClinicalTrials.gov)
✓ Trial adverse-event data found on ClinicalTrials.gov
Largest completed trials with posted results that list Nintedanib as a study intervention. The right-hand column of the signal table shows whether each FAERS term was also recorded in these trials, with a real denominator (14 of 40 signal terms matched).
- NCT02607722 — All-Case Surveillance of Ofev in Patients With IPF in Japan (N=10117, phase n/a; 448 AE terms posted; arms: IPF Patients Receiving Nintedanib)
Caveats: trial populations, doses and follow-up differ from the reporting population; AE terms are sponsor-coded and matched here by wording; absence from a trial list means the term was not reported above the sponsor's frequency threshold, not that it cannot occur.
Most frequently reported reactions
By raw co-report count, regardless of disproportionality. Common terms here are often the illness itself or generic outcomes.
| Reaction | Reports | PRR 95% CI · ROR · χ²/p | EBGM EB05 · IC025 | Label screen | Serious-only & strata | Trial cross-check |
|---|---|---|---|---|---|---|
| Diarrhoea (diarrhea) | 10,119 | 10.7 10.6–10.9ROR 15.4 · calibrated p 0.006 ✓ | 10.6 EB05 10.4 · IC025 +3.4 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 10.6 · 73% consumer | NCT02607722: 52/5,734 (0.9%) on Nintedanib (serious AE) |
| Nausea | 4,701 | 4.0 3.9–4.1ROR 4.6 · calibrated p 0.288 | 4.0 EB05 3.9 · IC025 +2.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 4.3 · 75% consumer | NCT02607722: 9/5,734 (0.2%) on Nintedanib (serious AE) |
| Dyspnoea (shortness of breath) | 4,035 | 4.8 4.7–5.0ROR 5.4 · calibrated p 0.196 | 4.8 EB05 4.7 · IC025 +2.2 3/3 methods agree | Not in label — unassessed | serious PRR 4.3 · 74% consumer | NCT02607722: 73/5,734 (1.3%) on Nintedanib (serious AE) |
| Cough | 3,260 | 7.9 7.7–8.2ROR 8.7 · calibrated p 0.051 | 7.8 EB05 7.6 · IC025 +2.9 3/3 methods agree | Not in label — unassessed | serious PRR 7.6 · 81% consumer | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Death | 3,193 | 2.5 2.4–2.6ROR 2.7 · calibrated p 0.744 | 2.5 EB05 2.4 · IC025 +1.3 3/3 methods agree | Outcome field, not a reaction | serious PRR 2.1 | NCT02607722: 51/5,734 (0.9%) on Nintedanib (serious AE) |
| Decreased appetite (loss of appetite) | 3,085 | 9.1 8.8–9.4ROR 10.0 · calibrated p 0.033 ✓ | 9.0 EB05 8.7 · IC025 +3.1 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.7 · 75% consumer | NCT02607722: 67/5,734 (1.2%) on Nintedanib (serious AE) |
| Weight decreased (weight loss) | 3,040 | 7.4 7.2–7.7ROR 8.1 · calibrated p 0.064 | 7.3 EB05 7.1 · IC025 +2.8 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 7.4 · 74% consumer | NCT02607722: 5/5,734 (0.1%) on Nintedanib (serious AE) |
| Fatigue (tiredness) | 2,961 | 2.6 2.5–2.7ROR 2.7 · calibrated p 0.719 | 2.6 EB05 2.5 · IC025 +1.3 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.9 · 79% consumer | not reported in cached trials |
| Vomiting | 2,756 | 4.0 3.8–4.1ROR 4.3 · calibrated p 0.333 | 4.0 EB05 3.8 · IC025 +1.9 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 3.5 · ♀ 64% (drug 42%) · 75% consumer | NCT02607722: 7/5,734 (0.1%) on Nintedanib (serious AE) |
| Idiopathic pulmonary fibrosis | 2,111 | 812.9 763.5–865.5ROR 871.9 · calibrated p 1e-16 ✓ | 364.4 EB05 351.6 · IC025 +8.3 3/3 methods agree | Likely indication confounding term in indications; also in warnings | serious n=2,088 | NCT02607722: 1000/5,734 (17.4%) on Nintedanib (serious AE) |
| Headache | 2,024 | 2.2 2.1–2.3ROR 2.3 · calibrated p 0.922 | 2.2 EB05 2.1 · IC025 +1.0 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 2.3 · 84% consumer | not reported in cached trials |
| Constipation | 2,019 | 6.3 6.1–6.6ROR 6.7 · calibrated p 0.112 | 6.3 EB05 6.0 · IC025 +2.6 3/3 methods agree | Not in label — unassessed | serious PRR 6.1 · 85% consumer | NCT02607722: 3/5,734 (0.1%) on Nintedanib (serious AE) |
| Abdominal pain upper | 1,876 | 6.2 5.9–6.5ROR 6.5 · calibrated p 0.120 | 6.1 EB05 5.9 · IC025 +2.5 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 6.6 · 85% consumer | NCT02607722: 2/5,734 (0.0%) on Nintedanib (serious AE) |
| Asthenia (weakness) | 1,712 | 3.1 2.9–3.2ROR 3.2 · calibrated p 0.567 | 3.1 EB05 2.9 · IC025 +1.5 3/3 methods agree | Not in label — unassessed | serious PRR 2.8 · 79% consumer | NCT02607722: 2/5,734 (0.0%) on Nintedanib (serious AE) |
| Abdominal discomfort | 1,645 | 6.7 6.4–7.0ROR 7.0 · calibrated p 0.099 | 6.6 EB05 6.3 · IC025 +2.6 3/3 methods agree | Labeled adverse reaction exact term | serious PRR 8.8 · 84% consumer | not reported in cached trials |
Unlabeled candidate signals
These flagged terms were not found in the FDA label text and do not match an artifact pattern. They are the pairs that would merit a structured assessment (temporality, dose-response, biological plausibility, consistency across databases, trial or cohort evidence). The screen has not done that; string-matching misses label wording, and a strong PRR can still be stimulated reporting, co-medication, or the disease itself.
- Lung diffusion test decreased — n=64, PRR 129.7
- Forced vital capacity decreased — n=99, PRR 121.3
- Kl-6 increased — n=25, PRR 89.1 (also seen in trial arm)
- Bendopnoea — n=22, PRR 79.7
- Lung transplant — n=234, PRR 47.2 (also seen in trial arm)
- Total lung capacity abnormal — n=22, PRR 41.2
- Total lung capacity decreased — n=79, PRR 34.9
- Chronic respiratory failure — n=57, PRR 33.8 (also seen in trial arm)
- Hypersensitivity pneumonitis — n=54, PRR 33.7 (also seen in trial arm)
- Faeces soft — n=311, PRR 30.2
Want to assess one of these properly? The runbook describes the Bradford Hill / trial-evidence workflow used on the assessment page, and handoff_top1000_signals.csv lists the strongest unassessed pairs across all drugs.
Common questions
What are the most reported side effects of Nintedanib?
In FDA FAERS, the most frequently co-reported reaction terms for Nintedanib are diarrhoea, nausea, dyspnoea, cough, decreased appetite, weight decreased. These are report counts, not rates: FAERS has no denominator, reporting is voluntary and uneven, and a term can be reported because of the illness being treated rather than the drug.
Does Nintedanib have an FDA boxed warning?
No. The FDA label retrieved for Nintedanib has no boxed warning; see the label's Warnings and Precautions for the recognised risks.
Do FAERS signals prove that Nintedanib causes these side effects?
No. A disproportionality signal (PRR, ROR) means a reaction is reported more often with this drug than with others in the database. That can reflect a real effect, but also the disease being treated, stimulated reporting after news or litigation, co-medications, or how reports are coded. Causality needs temporality, dose-response, biological plausibility, consistency across data sources and, ideally, trial or cohort evidence. This page screens each term against the FDA label and ClinicalTrials.gov results; it does not establish causation.
Sources & methods
- FDA label via openFDA (set ID 4d017c42-a823-452d-bc6f-0491dd9823e3, effective 20260402; matched on
openfda.generic_name.exact:"NINTEDANIB") - Bayesian shrinkage measures computed offline over all 1,317,300 cached pairs: BCPNN information component (IC, with Norén closed-form IC025) and MGPS empirical-Bayes geometric mean (EBGM, EB05) with a two-component gamma prior fitted by maximum marginal likelihood (α₁=0.57, β₁=0.02, α₂=1.42, β₂=0.70, w=0.17); unstratified
- FAERS pair statistics from the OpenPV build of 2026-09-14 (openFDA
count=aggregation, fieldpatient.drug.openfda.generic_name.exact, 1,111 reaction terms, min 3 co-reports); PRR/ROR with 95% CI, chi-square with Yates correction - Serious-only and stratified counts (serious:1, patient.patientsex, primarysource.qualification) from openFDA count queries; serious-only PRR uses the drug serious report total and the term global serious total (N_serious=11,882,979); strata shown only when n ≥ 20
- Seriousness and sex counts from openFDA
count=serious,patient.patientsex,seriousnessdeath - ClinicalTrials.gov API v2 (query
NINTEDANIB, results-bearing studies sorted by enrollment)
Page generated 2026-10-14. Label and PubChem text are retrieved automatically and may lag the current label; always check the current prescribing information. OpenPV is a beta research tool of the Open Source Medicine Foundation.