OFEV (Nintedanib) Uses and Clinical Applications
OFEV (nintedanib) is primarily used for the treatment of idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) in patients who have failed standard management for fibrotic interstitial lung disease (ILD). 1, 2
Primary Indications
Idiopathic Pulmonary Fibrosis (IPF)
- Nintedanib is recommended by the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association for IPF treatment 2
- Standard dosing: 150 mg twice daily, taken approximately 12 hours apart with food 2
- Clinical benefit: Significantly slows disease progression by reducing the annual rate of forced vital capacity (FVC) decline by approximately 125.2 ml compared to placebo 2, 3
Progressive Pulmonary Fibrosis (PPF)
- Conditionally recommended for PPF in patients who have failed standard management for fibrotic ILD other than IPF 1
- Evidence shows efficacy in reducing FVC decline by 100-125 mL compared to placebo 2
- Note: Standard management varies by patient and may include immunosuppressive treatment, antigen remediation, or observation 1
Mechanism of Action
Nintedanib is an oral intracellular tyrosine kinase inhibitor that:
- Blocks multiple pathways involved in fibrogenesis 1
- Has antifibrotic properties that reduce disease progression 4
- Works by inhibiting growth factor receptors implicated in pulmonary fibrosis 3
Clinical Efficacy
- Reduces the proportion of patients with >10% absolute decline in FVC (RR, 1.16; 95% CI, 1.06-1.27) 2
- May reduce acute exacerbations of IPF, though this benefit has not consistently reached statistical significance in all studies 2, 3
- Effective across mild, moderate, and severe stages of disease 4
- Treatment should be continued long-term as it slows but does not stop or reverse disease progression 2
Adverse Effects and Monitoring
Common Adverse Effects
- Gastrointestinal effects are most common:
- Elevated liver enzymes (3.2-3.6 times more likely than placebo) 1
Monitoring Requirements
- Liver function tests:
- Monthly for the first 3 months
- Every 3 months thereafter 2
- Regular assessment of symptoms and disease progression
- Monitoring for weight loss and dehydration 2
Management of Adverse Effects
- Dose reductions (from 150 mg twice daily to 100 mg twice daily)
- Treatment interruptions
- Anti-diarrheal medications 5
- Most adverse events do not lead to treatment discontinuation (<5% of patients) 2, 5
Special Considerations
- Not recommended during acute exacerbations of IPF (should be reserved for after resolution) 2
- Not recommended in patients with moderate to severe hepatic impairment 2
- Elderly patients may have higher discontinuation rates 2
- Patients with mild hepatic impairment require close monitoring and potential dose adjustment 2
Important Caveats
- Nintedanib slows but does not stop or reverse disease progression 2
- The evidence for use in specific types of non-IPF ILD manifesting PPF is still limited, and more research is needed 1
- Combination therapy with sildenafil has not shown additional benefits in patients with advanced disease 6
- Real-world data generally confirm the safety profile observed in clinical trials 5