What are the uses and side effects of Opipza?

Opipza (Nintedanib): Uses and Side Effects

Nintedanib (Opipza) is an oral tyrosine kinase inhibitor primarily used for treating idiopathic pulmonary fibrosis, progressive pulmonary fibrosis, and advanced non-small cell lung cancer of adenocarcinoma histology. Its mechanism of action involves competitively binding to kinase domains of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) 1.

Primary Uses

• Treatment of idiopathic pulmonary fibrosis (IPF) 2
• Management of progressive pulmonary fibrosis (PPF) 3
• Treatment of advanced non-small cell lung cancer with adenocarcinoma histology 1
• Potential second-line therapy for lymphangioleiomyomatosis in patients not controlled by standard treatment with mTOR inhibitors 4

Pharmacokinetics

• Reaches maximum plasma concentration approximately 2-4 hours after oral administration 1
• Has a terminal elimination half-life of about 10-15 hours 1
• Shows dose-proportional exposure increases within the investigated dose range 1
• Metabolized via hydrolytic ester cleavage, with less than 1% eliminated in urine 1
• Minimal accumulation after repeated twice-daily dosing 1

Dosing

• Typical dosage is 150 mg orally twice daily 4
• Dose can be reduced to 100 mg twice daily in case of side effects or hepatotoxicity 4
• Not recommended for patients with moderate or severe hepatic impairment 1
• Patients with mild hepatic impairment should be closely monitored with dose adjustments as needed 1

Common Side Effects

• Gastrointestinal effects:

  • Diarrhea (most common adverse event) 2
  • Nausea 2
  • Vomiting 2
  • Abdominal pain 4

• Hepatic effects:

  • Elevated liver enzymes, particularly in the first few months of treatment 2
  • Regular monitoring of liver enzymes is recommended 2

• Other effects:

  • Bleeding events (rare) 2
  • Cardiovascular adverse events (rare) 2

Management of Side Effects

• Gastrointestinal side effects can be managed through:

  • Dose reduction from 150 mg to 100 mg twice daily 4, 2
  • Treatment interruptions 2
  • Use of anti-diarrheal medications 2

• Liver enzyme elevations:

  • Regular monitoring of liver function, especially during the first few months 2
  • Dose reduction or interruption if significant elevations occur 2

Special Populations and Considerations

• No dose adjustments required for:

  • Sex differences 1
  • Renal function impairment 1
  • Ethnicity, low body weight, older age, or smoking status (effects are within inter-patient variability range) 1

• Cautions:

  • Not recommended for patients with moderate to severe hepatic impairment 1
  • Potential drug interactions with potent inhibitors or inducers of P-glycoprotein transporter 1
  • Limited data on use in elderly patients or those with advanced disease, though some evidence suggests higher treatment discontinuation rates in these populations 2

Long-term Treatment Considerations

• Long-term treatment data from INBUILD-ON extension study shows consistent safety profile with earlier trials 3
• Continued treatment shows stabilization of forced vital capacity (FVC) decline in progressive pulmonary fibrosis 3
• Adverse events leading to discontinuation occur at a rate of 16.7 per 100 patient-years in long-term use 3

Clinical Efficacy

• In idiopathic pulmonary fibrosis, nintedanib slows the decline in forced vital capacity 2
• In lymphangioleiomyomatosis, nintedanib stabilized FEV1 during treatment, with slight decline observed after treatment cessation 4
• Long-term treatment data supports continued efficacy in progressive pulmonary fibrosis 3