What is Nintedanib?
Nintedanib, sold under the brand name Ofev, is an oral medication used to treat several forms of interstitial lung disease (ILD), including idiopathic pulmonary fibrosis (IPF), systemic sclerosis-associated ILD (SSc-ILD), and other chronic fibrosing ILDs with a progressive phenotype [1.2.1, 1.4.3]. It belongs to a class of drugs known as tyrosine kinase inhibitors (TKIs) [1.3.5]. By blocking multiple pathways involved in the signaling of growth factors like platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF), nintedanib helps to slow down the progression of lung scarring (fibrosis) [1.3.1, 1.3.5]. While effective in managing these serious lung conditions, its mechanism of action also contributes to a notable profile of side effects, chief among them being gastrointestinal issues [1.2.2].
The High Incidence of Nintedanib-Induced Diarrhea
Diarrhea is not just a possible side effect of nintedanib; it is the most frequently reported one [1.6.3]. Data from major clinical trials consistently highlights its prevalence:
- IPF Studies (INPULSIS trials): Approximately 62% of patients treated with nintedanib experienced diarrhea, compared to just 18% in the placebo group [1.2.2, 1.4.5].
- SSc-ILD Study (SENSCIS trial): The incidence was even higher, with 76% of nintedanib patients reporting diarrhea versus 32% of placebo patients [1.3.3, 1.4.3].
- Chronic Fibrosing ILDs with a Progressive Phenotype Study (INBUILD trial): Diarrhea was reported in 67% of nintedanib patients, compared to 24% in the placebo group [1.3.3, 1.8.1].
Most events are characterized as mild to moderate in intensity and typically occur within the first three months of starting treatment [1.4.4, 1.4.5]. While manageable for most, this side effect is significant enough that it can lead to dose reductions or treatment discontinuation. Across various studies, diarrhea led to permanent dose reductions in 11% to 22% of patients and treatment discontinuation in 5% to 7% of patients [1.2.3].
Why Does Nintedanib Cause Diarrhea?
The exact pathophysiology of nintedanib-induced diarrhea is not fully understood, but research points to several potential mechanisms related to its function as a TKI [1.3.1]. Experts have proposed two primary theories:
- Receptor Inhibition Effects: Nintedanib inhibits VEGF, PDGF, and FGF receptors. The inhibition of these receptors may interfere with the normal function and turnover of cells in the intestinal lining (enterocytes), potentially leading to apoptosis (cell death) and impaired mucosal integrity [1.3.1, 1.3.6]. Inhibition of the VEGF receptor, for example, might disrupt the capillary network in the intestinal mucosa, leading to ischemia-like effects [1.3.1].
- Direct Mucosal Inflammation: Since nintedanib and its metabolites are primarily excreted through feces (over 90%), it's hypothesized that the drug may have a direct inflammatory or irritant effect on the intestinal epithelium as it passes through the digestive system [1.3.2, 1.3.6]. This could lead to a condition similar to colitis [1.3.2].
A Proactive Approach to Managing Diarrhea
For patients starting nintedanib, proactive management is key to maintaining quality of life and treatment adherence. Management is a multi-step process that should always be guided by a healthcare provider [1.5.2].
Initial Steps and Dietary Adjustments
At the first sign of diarrhea, patients should focus on adequate hydration with water, broth, or electrolyte-containing sports drinks to prevent dehydration [1.6.3, 1.7.1]. Dietary changes can also have a significant impact. It is often recommended to:
- Adopt a bland diet: The BRAT diet (bananas, rice, applesauce, toast) is low in fiber and easy to digest, which can help firm up stools [1.4.2, 1.7.4].
- Avoid trigger foods: Patients should avoid greasy, fried, spicy, or high-fiber foods (like beans and whole grains), as well as dairy products, alcohol, and caffeine, which can exacerbate symptoms [1.7.3, 1.7.5].
- Eat small, frequent meals: This can be easier on the digestive system than three large meals [1.4.6].
Medical Interventions
If dietary changes are not enough, medical intervention is necessary.
- Antidiarrheal Medication: Loperamide (Imodium) is the standard first-line treatment and should be used as directed by a doctor at the onset of symptoms [1.2.2, 1.4.3].
- Dose Modification: If diarrhea persists or is severe, a healthcare provider may recommend a temporary treatment interruption or a dose reduction of nintedanib (e.g., from 150 mg twice daily to 100 mg twice daily) [1.2.3]. The goal is to control the side effect while maintaining the therapeutic benefit of the drug. Treatment can often be resumed at the full or reduced dose once symptoms improve [1.2.3, 1.7.2].
- Other Medications: In some resistant cases, other medications like budesonide (a corticosteroid with localized gut action) or ramosetron (a 5-HT3 receptor antagonist) have been used with some success, though this is less common [1.3.1, 1.3.2].
| Management Strategy | Description | Best For | Key Consideration |
|---|---|---|---|
| Diet & Hydration | Adopting a bland diet (BRAT), avoiding trigger foods, and increasing fluid intake [1.7.3, 1.7.4]. | Mild, initial episodes of diarrhea. | A foundational strategy for all levels of severity. |
| Antidiarrheal Medication | Using over-the-counter loperamide as directed at the first sign of loose stools [1.2.2]. | Mild to moderate diarrhea that doesn't resolve with diet alone. | Should be readily available for patients starting nintedanib. |
| Dose Interruption | Temporarily stopping nintedanib until diarrhea resolves to a manageable level (Grade 1 or baseline) [1.2.3]. | Moderate to severe, persistent diarrhea. | Allows the gut to recover; treatment is typically resumed. |
| Dose Reduction | Permanently lowering the daily dose of nintedanib, usually to 100mg twice daily [1.2.3, 1.4.3]. | Persistent diarrhea that is not controlled by other measures, allowing for long-term continuation of therapy. | The efficacy of the lower dose must be balanced with side effect management. |
When to Contact a Doctor
It is crucial for patients to maintain open communication with their healthcare team. A doctor should be contacted if diarrhea is severe, persistent, or accompanied by other symptoms like severe abdominal pain, dehydration (dizziness, low urine output), fever, or blood in the stool [1.6.2, 1.6.3].
Conclusion
To answer the question, can nintedanib cause diarrhea?—the evidence is overwhelmingly clear: it is the most common side effect of the therapy. However, it is also a manageable one for the majority of patients. Through a combination of proactive dietary strategies, prompt use of antidiarrheal agents like loperamide, and physician-guided dose adjustments, most individuals can continue to benefit from nintedanib's ability to slow the progression of their lung disease without letting this side effect control their life.
For more information from the manufacturer on managing side effects, you can visit the Ofev Patient Support website. [1.4.5]
