What are the common adverse effects and frequency of adverse reactions to Ofev (nintedanib)?

Adverse Effects and Frequency of Adverse Reactions to Ofev (Nintedanib)

Gastrointestinal adverse effects are the most common reactions to nintedanib (Ofev), with diarrhea occurring in 60-75% of patients, followed by nausea, vomiting, abdominal pain, and decreased appetite, while hepatic enzyme elevations occur in approximately 14% of patients. 1, 2

Gastrointestinal Adverse Effects

Diarrhea

• Occurs in 60-75% of patients 1, 2
• Most common adverse effect
• Usually mild to moderate in severity 3
• Rarely leads to permanent discontinuation (<5% of cases) 2, 3
• Management: anti-diarrheal medications, dose reduction, or temporary interruption 3

Other GI Effects

• Nausea (reported in 11.8-37% of patients) 4
• Vomiting (3.6 times more common than placebo) 1
• Abdominal pain (4.2 times more common than placebo) 1
• Decreased appetite/anorexia (2.8 times more common than placebo) 1
• Weight loss (3.7 times more common than placebo) 1

Hepatic Adverse Effects

• Elevated liver enzymes:
  • Aspartate aminotransferase (AST) elevations (3.2 times more common than placebo) 1
  • Alanine aminotransferase (ALT) elevations (3.6 times more common than placebo) 1
• Regular monitoring recommended:
  • Monthly for first 3 months of treatment
  • Every 3 months thereafter 1, 2
• Nintedanib is not recommended in patients with moderate to severe hepatic impairment 5

Other Adverse Effects

• Increased risk of bleeding (rare but requires monitoring) 3
• Cardiovascular events (uncommon but requires caution) 3
• Arterial thromboembolic events (uncommon)
• Venous thromboembolism (uncommon)
• Hypertension (uncommon)
• Headache (uncommon)

Frequency and Impact on Treatment

• Any adverse event: 1.1 times more common than placebo 1
• Adverse events leading to dose reduction: 7.9 times more common than placebo 1
• Adverse events leading to treatment discontinuation: 1.9 times more common than placebo 1
• Discontinuation rates in real-world studies: 32-40% 4, 6

Risk Factors for Adverse Effects

Several patient factors increase the risk of experiencing adverse effects:

• Low body mass index (BMI) - significant risk factor for both nausea and diarrhea 7
• Poor performance status - risk factor for nausea 7
• Full dosage (150 mg twice daily) at treatment initiation - risk factor for nausea 7
• Systemic sclerosis-associated ILD patients experience significantly more nausea than idiopathic interstitial pneumonia patients (37% vs 11.8%) 4

Management Strategies

1. Dose Adjustments:

   • Standard dose: 150 mg twice daily
   • Reduced dose: 100 mg twice daily if not tolerated 2
   • Temporary interruptions as needed 3

2. Supportive Medications:

   • Anti-diarrheal medications for GI symptoms 3
   • Prednisolone may help prevent diarrhea in some patients 7

3. Monitoring:

   • Liver function tests monthly for first 3 months, then every 3 months 1, 2
   • Regular assessment of symptoms and disease progression
   • Monitor for weight loss and dehydration

Special Populations

• Elderly patients: May have higher discontinuation rates 3
• Advanced disease: May have higher discontinuation rates 3
• Mild hepatic impairment: Requires close monitoring and potential dose adjustment 5
• Moderate/severe hepatic impairment: Nintedanib not recommended 5
• Renal impairment: No dose adjustment needed 5

Drug Interactions

• Caution with P-glycoprotein inhibitors and CYP3A4 inhibitors/inducers 2, 5
• Less than 1% of drug-related radioactivity is eliminated in urine 5

The adverse effect profile of nintedanib is generally consistent between clinical trials and real-world studies, with gastrointestinal effects predominating but rarely leading to permanent discontinuation when properly managed 3, 6.