Yes, nintedanib commonly causes diarrhea (loose motion)
Diarrhea is the most frequent adverse event associated with nintedanib, occurring 2.8 times more often than placebo, and is the primary reason for treatment discontinuation. 1, 2
Magnitude of the Problem
The evidence from major clinical trials consistently demonstrates that gastrointestinal adverse events, particularly diarrhea, are the hallmark side effect of nintedanib:
- Diarrhea occurs 2.8 times more frequently with nintedanib compared to placebo in patients with progressive pulmonary fibrosis 1
- In the INPULSIS trials (1,066 patients with IPF), patients treated with nintedanib reported significantly more diarrhea compared to placebo 2
- In long-term follow-up data from INBUILD-ON, diarrhea remained the most frequent adverse event, though 90% of cases were mild to moderate in severity 3
Additional Gastrointestinal Effects
Beyond diarrhea, nintedanib increases other gastrointestinal adverse events 1:
- Nausea (3.1 times more common)
- Vomiting (3.6 times more common)
- Abdominal pain (4.2 times more common)
- Anorexia/decreased appetite (2.8 times more common)
- Weight loss (3.7 times more common)
Clinical Impact
Gastrointestinal adverse events lead to permanent dose reduction 7.9 times more often and treatment discontinuation 1.9 times more often than placebo 1. The discontinuation rate due to adverse events in long-term treatment is 16.7 per 100 patient-years 3.
Risk Factors for Nintedanib-Induced Diarrhea
Recent research has identified specific predictors 4:
- IPF diagnosis (versus other ILDs)
- No concurrent corticosteroid therapy
- Higher nintedanib dose per body surface area
- Lower baseline FVC (≤80%)
- Smaller body surface area 5
Time Course
Diarrhea typically occurs within the first 3 months of treatment, with median onset around 119.5 days 6. However, it can occur at any point during therapy 3.
Important Clinical Guidance
The 2015 ATS/ERS/JRS/ALAT guidelines explicitly state: "Adverse effects were commonly reported with nintedanib therapy, specifically diarrhea, and patients must be informed of this when deciding on treatment" 2.
Despite these significant gastrointestinal side effects, nintedanib provides meaningful clinical benefit by slowing FVC decline and disease progression, which is why guidelines conditionally recommend its use with appropriate patient counseling about expected adverse events.