Nintedanib is a potent, orally administered, small molecule tyrosine kinase inhibitor (TKI) that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). It is a first-in-class antifibrotic agent approved for the treatment of specific progressive fibrosing interstitial lung diseases (ILDs). In the Indian context, it is a critical therapy for slowing disease progression in idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD), conditions with significant morbidity and mortality.
Adult: 150 mg twice daily (approximately 12 hours apart). The 100 mg capsule strength is used for dose adjustment.
Note: Administer orally with food to reduce gastrointestinal upset. Swallow the soft gelatin capsule whole with a glass of water. Do not chew or crush. If a dose is missed, it can be taken within a few hours, but skip if it is close to the next dose. Do not take two doses at the same time.
Nintedanib is a competitive inhibitor that targets the intracellular ATP-binding pocket of multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). It primarily inhibits platelet-derived growth factor receptor (PDGFR-α and β), fibroblast growth factor receptor (FGFR 1-3), and vascular endothelial growth factor receptor (VEGFR 1-3). These pathways are crucially involved in the proliferation, migration, and transformation of lung fibroblasts into myofibroblasts, which are key effector cells in pulmonary fibrosis. By blocking these pro-fibrotic signaling pathways, nintedanib reduces the rate of lung function decline.
Pregnancy: Category D. Nintedanib is contraindicated in pregnancy. Animal studies have shown teratogenicity and embryofetal lethality. Women of childbearing potential must use highly effective contraception during treatment and for at least 3 months after the last dose.
Driving: Nintedanib has a low potential to impair ability to drive or use machines. However, patients experiencing fatigue or dizziness should exercise caution.
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Increase nintedanib exposure (AUC). Co-administration not recommended. If unavoidable, monitor closely for adverse effects. | Major |
| Strong CYP3A4 Inducers (e.g., Rifampicin, Carbamazepine, Phenytoin, St. John's Wort) | Decrease nintedanib exposure (AUC), potentially reducing efficacy. Co-administration should be avoided. | Major |
| P-glycoprotein (P-gp) Inhibitors (e.g., Verapamil, Amiodarone, Quinidine) | May increase nintedanib exposure. Monitor for increased adverse reactions. | Moderate |
| Anticoagulants (e.g., Warfarin, NOACs like Apixaban, Rivaroxaban) and Antiplatelets (e.g., Clopidogrel) | Increased risk of bleeding due to nintedanib's potential to inhibit VEGFR and PDGFR affecting platelet function. Monitor for signs of bleeding. | Major |
| Other Hepatotoxic Drugs | Increased risk of liver injury. Avoid concomitant use with known hepatotoxins. Monitor LFTs more frequently. | Moderate |