Side Effects of Nintedanib
Gastrointestinal adverse effects dominate the side effect profile of nintedanib, with diarrhea occurring in approximately 62-72% of patients compared to 18-26% on placebo, though this rarely leads to permanent discontinuation. 1
Most Common Adverse Effects
Gastrointestinal Effects (Most Frequent)
- Diarrhea is the most common side effect, occurring 2.8 times more frequently than placebo, affecting 61-72% of nintedanib-treated patients 1, 2, 3
- Nausea occurs 3.1 times more frequently than placebo 1, 4
- Vomiting occurs 3.6 times more frequently than placebo 1, 4
- Abdominal pain occurs 4.2 times more frequently than placebo 1, 4
- Anorexia occurs 2.8 times more frequently than placebo 4
Systemic Effects
- Weight loss occurs 3.7 times more frequently than placebo and requires active monitoring 1, 4
- Fatigue is reported but less common than GI effects 5
Hepatic Effects
- Elevated AST occurs 3.2 times more frequently than placebo 1, 4
- Elevated ALT occurs 3.6 times more frequently than placebo 1, 4
- Liver enzyme monitoring is mandatory monthly for 3 months, then every 3 months 1
Treatment Discontinuation and Dose Adjustments
- Adverse events lead to permanent dose reduction 7.9 times more frequently with nintedanib than placebo 1, 4
- Treatment discontinuation occurs 1.9 times more frequently with nintedanib (22% vs 14.5% placebo) 1, 2
- Diarrhea specifically leads to discontinuation in only 6.3% of patients despite its high frequency 2
- In real-world studies, 48.2% of patients required at least one dose reduction and/or treatment interruption 2
Management Algorithm for Adverse Effects
For Persistent Diarrhea or GI Symptoms
- Reduce dose to 100 mg twice daily (from standard 150 mg twice daily) 1, 4
- Consider temporary treatment interruption if symptoms persist 1
- Use anti-diarrheal medications as needed 6, 2
- Implement aggressive GERD management with proton pump inhibitors 1
For Elevated Liver Enzymes
- Monitor liver function tests monthly for first 3 months, then every 3 months 1
- Consider dose reduction or interruption based on severity 4
Special Population Considerations
Gender Differences
- Nausea, vomiting, and dose reductions are more common in female patients compared to male patients 2
Elderly and Advanced Disease
- Greater rates of treatment discontinuation observed in elderly patients and those with advanced disease 6
- Consider starting at reduced dose (100 mg twice daily) in patients with severe chronic kidney disease (creatinine clearance <30 mL/min) 4
Rare but Important Adverse Events
- Bleeding events are rarely reported in real-world data 6
- Cardiovascular adverse events are rarely reported 6
- Serious adverse events occurred in 44.3% of nintedanib patients versus 49.5% on placebo, suggesting no overall increase in serious events 2
Key Clinical Pitfall
The high frequency of diarrhea (>60% of patients) should not automatically lead to treatment discontinuation—dose reduction to 100 mg twice daily manages symptoms in most patients and allows continuation of therapy 1. Real-world data confirm that despite the high incidence of GI side effects, these are manageable with dose adjustments and symptomatic treatment, allowing most patients to remain on therapy 6, 2.