What is the use and dosage of Nintedanib (generic name) in treating idiopathic pulmonary fibrosis (IPF) and non-small cell lung cancer (NSCLC)?

Nintedanib for Idiopathic Pulmonary Fibrosis (IPF) and Non-Small Cell Lung Cancer (NSCLC)

Nintedanib is recommended at a dose of 150 mg twice daily for patients with IPF to slow disease progression, and as a second-line treatment option in combination with docetaxel for patients with adenocarcinoma NSCLC who have progressed after first-line chemotherapy. 1

Mechanism of Action

• Nintedanib is an intracellular inhibitor of multiple tyrosine kinases that targets growth factor receptors including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) 1, 2
• The drug has both antifibrotic and antiangiogenic properties, making it effective for both IPF and certain cancers 2, 3

Use in Idiopathic Pulmonary Fibrosis (IPF)

Dosage and Administration

• The recommended dose for IPF is 150 mg twice daily taken with food 1, 4
• Nintedanib is rapidly absorbed after oral administration with peak plasma concentrations reached within 2-4 hours 2, 5
• The terminal elimination half-life is approximately 10-15 hours 2

Efficacy in IPF

• Nintedanib significantly reduces the annual rate of decline in forced vital capacity (FVC) by approximately 125 ml compared to placebo, indicating slowed disease progression 1, 4
• The drug reduces the risk of acute exacerbations of IPF (HR 0.16; 95% CI, 0.04-0.70) 1, 4
• While nintedanib shows benefits for disease progression, no significant effect on overall mortality has been demonstrated 1

Patient Selection for IPF Treatment

• Nintedanib is indicated for patients with confirmed IPF diagnosis regardless of disease severity 1
• Treatment should be initiated early in the disease course to preserve lung function 1
• Patients must be informed about potential adverse effects, particularly gastrointestinal effects, before starting treatment 1

Use in Non-Small Cell Lung Cancer (NSCLC)

Dosage and Administration for NSCLC

• For advanced NSCLC of adenocarcinoma histology, nintedanib is administered at 200 mg twice daily in combination with docetaxel as second-line therapy 1, 6, 3
• Treatment is continued until disease progression or unacceptable toxicity 6, 3

Patient Selection for NSCLC Treatment

• Nintedanib/docetaxel is specifically recommended for patients with adenocarcinoma NSCLC who have progressed after first-line chemotherapy 1, 6
• This combination is particularly beneficial for patients progressing within 9 months from the start of first-line chemotherapy 6
• Patients should have adequate organ function and performance status (PS 0-2) 1, 6

Adverse Effects and Management

Common Adverse Effects

• Gastrointestinal effects are most common, with diarrhea occurring in approximately 62% of patients taking nintedanib versus 18% on placebo 1, 4
• Other common adverse events include nausea, vomiting, abdominal pain, decreased appetite, and weight loss 1
• Elevated liver enzymes (AST/ALT) may occur and require monitoring 1

Dose Modifications

• For persistent diarrhea, temporary dose reduction to 100 mg twice daily or treatment interruption may be necessary 1
• For patients with mild hepatic impairment, close monitoring is required with dose adjustment if needed 2
• Nintedanib is not recommended for patients with moderate or severe hepatic impairment 2

Special Considerations

Drug Interactions

• Nintedanib has a low potential for drug-drug interactions with medications metabolized by cytochrome P450 enzymes 2
• Concomitant use with potent P-glycoprotein inhibitors or inducers may affect nintedanib pharmacokinetics and should be monitored 2, 5

Monitoring Requirements

• Regular assessment of liver function tests before and during treatment 1, 2
• Monitoring for gastrointestinal adverse effects and appropriate management 1, 4
• Periodic assessment of disease progression through pulmonary function tests in IPF patients 1

Progressive Pulmonary Fibrosis (PPF) Beyond IPF

• Nintedanib is also suggested for treatment of progressive pulmonary fibrosis (PPF) in patients with non-IPF fibrotic interstitial lung diseases who have failed standard management 1
• In patients with PPF, nintedanib reduced annual FVC decline by approximately 107 ml compared to placebo 1
• The benefit varies by underlying disease type, with greater FVC preservation in CTD-related ILD (106.2 ml/yr), fibrotic NSIP (141.7 ml/yr), and fibrotic occupational lung disease (252.8 ml/yr) 1

Clinical Pearls and Pitfalls

• Diarrhea, the most common adverse effect, typically occurs within the first 3 months of treatment but can be managed with dose adjustments and antidiarrheal medications 1, 4
• Nintedanib should be temporarily withheld before major surgery due to potential interference with wound healing 2
• The cost of nintedanib may limit feasibility and use, which should be factored into treatment decisions 1
• Unlike some other treatments for IPF, nintedanib does not require regular blood monitoring for bone marrow toxicity 1