Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: plateletderived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, colony stimulating factor 1 receptor (CSF1R), and Fms-like tyrosine kinase 3 (FLT-3). These kinases except for FLT-3 have been implicated in pathogenesis of interstitial lung diseases (ILD). Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these kinases and blocks the intracellular signaling cascades, which have been demonstrated to be involved in the pathogenesis of fibrotic tissue remodeling in ILD. Nintedanib also inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT-3 and nRTK inhibition to nintedanib efficacy in ILD is unknown.

OFEV is a kinase inhibitor indicated in adults for:

• Treatment of idiopathic pulmonary fibrosis (IPF). 
• Treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype 
• Slowing the rate of decline in pulmonary function in patients with systemic sclerosis-associated
• interstitial lung disease (SSc-ILD) 

Recommended dosage: 150 mg taken orally twice daily approximately 12 hours apart taken with food.

Recommended dosage in patients with mild hepatic impairment (Child Pugh A): 100 mg taken orally twice daily approximately 12 hours apart taken with food. 

Consider temporary dose reduction to 100 mg, treatment interruption, or discontinuation for management of adverse reactions. 

Prior to treatment initiation, conduct liver function tests in all patients and a pregnancy test in females of reproductive potential.

Most common adverse reactions (≥5%) are: diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, decreased appetite, headache, weight decreased, and hypertension.

None.

• Hepatic impairment: OFEV is not recommended for use in patients with moderate or severe hepatic impairment. In patients with mild hepatic impairment (Child Pugh A), the recommended dosage is 100 mg twice daily approximately 12 hours apart taken with food. Consider treatment interruption, or discontinuation for management of adverse reactions in these patients. 
• Elevated liver enzymes and drug-induced liver injury: ALT, AST, and bilirubin elevations have occurred with OFEV, including cases of drug-induced liver injury. In the postmarketing period, non-serious and serious cases of drug-induced liver injury, including severe liver injury with fatal outcome, have been reported. The majority of hepatic events occur within the first three months of treatment. Liver enzyme and bilirubin increases were reversible with dose modification or interruption in the majority of cases. Monitor ALT, AST, and bilirubin prior to initiation of treatment, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Temporary dosage reductions or discontinuations may be required.
• Gastrointestinal disorders: Diarrhea, nausea, and vomiting have occurred with OFEV. Treat patients at first signs with adequate hydration and antidiarrheal medicine (e.g., loperamide) or anti-emetics. Discontinue OFEV if severe diarrhea, nausea, or vomiting persists despite symptomatic treatment.
• Embryo-Fetal toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use highly effective contraception. Advise women taking oral hormonal contraceptives experiencing vomiting, diarrhea, or other conditions where the drug absorption may be reduced to use alternative highly effective contraception. 
• Arterial thromboembolic events have been reported. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. 
• Bleeding events have been reported. Use OFEV in patients with known bleeding risk only if anticipated benefit outweighs the potential risk.
• Gastrointestinal perforation has been reported. Use OFEV with caution when treating patients with recent abdominal surgery, previous history of diverticular disease or receiving concomitant corticosteroids or NSAIDs. Discontinue OFEV in patients who develop gastrointestinal perforation. Only use OFEV in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk.
• Nephrotic range proteinuria has been reported. Consider treatment interruption in patients who develop new or worsening proteinuria.