Nintedanib (Ofev)

Indications

Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]])

  • FDA Approval for Idiopathic Pulmonary Fibrosis: Oct, 2014
  • INPULSIS Trials (NEJM, 2014) [MEDLINE]
    • Nintedanib Decreased the Decline in FVC
    • However, Nintedanib Did Not Not Decrease the Time to First Exacerbation

Pharmacology

  • Tyrosine Kinase Inhibitor

Metabolism

  • xxx

Administration

  • PO: xxx

Dose Adjustment

  • Hepatic: not recommended for use in moderate-severe liver disease
  • Renal: xxx

Adverse Effects

Gastrointestinal Adverse Effects

  • Abdominal Pain (see Abdominal Pain, [[Abdominal Pain]])
  • Anorexia (see Anorexia, [[Anorexia]])
  • Diarrhea (see Diarrhea, [[Diarrhea]])
    • INPULSIS Trials: diarrhea occurred in 61.5% of cases, as compared 18.6% of placebo-treated controls
    • INPULSIS Trials: however, diarrhea resulted in drug stoppage in <5% of study patients
  • Elevated Liver Function Tests (LFT’s) (see Drug-Induced Hepatotoxicity, [[Drug-Induced Hepatotoxicity]]): occurs in 14% of cases within 1 year
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
  • Weight Loss (see Weight Loss, [[Weight Loss]])

Neurologic Adverse Effects

  • Headache (see Headache, [[Headache]]): occurs in 8% of cases within 1 year

Otolaryngologic Adverse Effects

Renal Adverse Effects

  • Hypertension (see Hypertension, [[Hypertension]]): occurs in 5% of cases within 1 year

Reproductive Adverse Effects

  • Teratogenicity

Other Adverse Effects

  • xxx
  • xxx
  • xxx
  • xxx

References

  • Efficacy of a tyrosine kinase inhibitor in idiopathic pulmonary fibrosis. N Engl J Med 2011;365(12):1079-1087 [MEDLINE]
  • Anti-fibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmcol Exp Ther 2014;349:209-230 [MEDLINE]
  • Design of the INPULSIS™ trials: two phase 3 trials of nintedanib in patients with idiopathic pulmonary fibrosis. Respir Med. 2014 Jul;108(7):1023-30. doi: 10.1016/j.rmed.2014.04.011. Epub 2014 Apr 29 [MEDLINE]
  • INPULSIS Trial: Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2071-82 [MEDLINE]
  • IPF: evolving concepts. Mayo Clin Proc 2014;9:1130-1142 [MEDLINE]
  • Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J. 2015 May;45(5):1434-45. doi: 10.1183/09031936.00174914. Epub 2015 Mar 5 [MEDLINE]
  • Safety, tolerability and appropriate use of nintedanib in idiopathic pulmonary fibrosis. Respir Res. 2015 Sep 24;16:116. doi: 10.1186/s12931-015-0276-5 [MEDLINE]
  • Efficacy of Nintedanib in Idiopathic Pulmonary Fibrosis Across Pre-specified Subgroups in INPULSIS®. Am J Respir Crit Care Med. 2015 Sep 22 [MEDLINE]