Generic
Nintedanib
8 brands available in the market
At a glance
Nintedanib is a tyrosine kinase inhibitor used for Idiopathic Pulmonary Fibrosis (IPF), chronic fibrosing interstitial lung diseases and systemic sclerosis-associated ILD, and with docetaxel in NSCLC.
Description
Nintedanib is a small molecule, competitive, triple angiokinase inhibitor that targets multiple receptor tyrosine kinases (PDGFR, FGFR, VEGFR, FLT3) and non-receptor tyrosine kinases (Lck, Lyn, Src). It inhibits lung fibroblast proliferation and migration and induces apoptosis of tumor cells.
Indications
- Idiopathic Pulmonary Fibrosis (IPF)
- Chronic fibrosing interstitial lung diseases (progressive phenotype)
- Systemic sclerosis-associated interstitial lung disease (SSc-ILD)
- Locally advanced, metastatic or locally recurrent NSCLC (with docetaxel)
Therapeutic class
Tyrosine Kinase Inhibitor
Pharmacological class
Triple Angiokinase Inhibitor
Pharmacology
Nintedanib binds to ATP-binding pocket of multiple RTKs (PDGFR, FGFR, VEGFR, FLT3) and nRTKs (Lck, Lyn, Src) to inhibit their activity. It prevents lung fibroblast proliferation and migration and induces apoptosis of tumor cells.
Mechanism of action
Reduces lung fibrosis and prevents tumor cell growth.
Dosage
IPF/ILD/SSc-ILD:
- 150 mg twice daily approximately 12 hours apart
- 100 mg twice daily if not tolerated
NSCLC (with Docetaxel):
- 200 mg twice daily on days 2-21 of 21-day cycle
Administration
- Take with food
- Swallow capsules whole; do not chew or crush
- Take approximately 12 hours apart
Missed dose
If you miss a dose, take at next scheduled time; do not take additional dose.
Side effects
Common Side Effects (≥10%):
- Diarrhea (62.4%)
- Nausea
- Vomiting
- Abdominal pain
- Decreased appetite
- Weight decreased
- Hepatic enzyme increased
Serious: Hepatotoxicity, hemorrhage, GI perforation, arterial thromboembolic events
Precautions & warnings
- Manage diarrhea with hydration and loperamide
- Monitor hepatic enzymes regularly (first 3 months)
- Patients with low body weight (<65 kg), Asian and female have higher risk of liver enzyme elevations
- Risk of bleeding; caution with anticoagulants
- Risk of GI perforation; start 4 weeks after abdominal surgery
- Can cause fetal harm; use effective contraception
Contraindications
- Hypersensitivity
- Peanut or soya allergy
- Moderate or severe hepatic impairment (Child Pugh B or C)
- Pregnancy
Drug interactions
- P-gp inhibitors (ketoconazole) increase nintedanib exposure
- P-gp inducers (rifampicin) decrease nintedanib exposure
- Low likelihood of CYP-mediated interactions
Food interactions
Take with food for better absorption.
Use in pregnancy
Use in Pregnancy: Nintedanib is highly unsafe during pregnancy; definite evidence of severe fetal harm. Do not use.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Use in Lactation: Nintedanib is contraindicated during breastfeeding; discontinue breastfeeding.
Pediatric use
Safety and efficacy not established in children aged 0-18 years.
Geriatric use
No overall differences observed in patients ≥65 years; patients ≥75 years may require dose reduction.
Renal / hepatic impairment
Renal Impairment: No dose adjustment needed in mild-moderate renal impairment; not studied in severe renal impairment.
Hepatic Impairment: Mild (Child Pugh A): 100 mg twice daily; Moderate/Severe (Child Pugh B/C): Not recommended.
Overdose effects
No specific treatment for overdose; symptomatic supportive measures.
Storage conditions
Store in a cool and dry place, protected from light; do not store above 25°C.
Chemical structure
Nintedanib