Overview
11 DESCRIPTION Nintedanib Capsules contain nintedanib, a kinase inhibitor [see Mechanism of Action (12.1) ] . Nintedanib is presented as the ethanesulfonate salt (esylate), with the chemical name 1 H -Indole-6-carboxylic acid, 2,3- dihydro-3-[[[4-[methyl[(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-,methyl ester, (3Z)-, ethanesulfonate (1:1).
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Nintedanib is a small molecule that inhibits multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: platelet-derived 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).
Indications
- 1 INDICATIONS AND USAGE Nintedanib Capsules is a kinase inhibitor indicated in adults for: Treatment of idiopathic pulmonary fibrosis (IPF) ( 1.1 ) Treatment of chronic fibrosing interstitial lung diseases (ILDs) with a progressive phenotype ( 1.2 ) 1.1 Idiopathic Pulmonary Fibrosis Nintedanib Capsules is indicated for the treatment of adults with idiopathic pulmonary fibrosis (IPF). 1.2 Chronic Fibrosing Interstitial Lung Diseases with a Progressive Phenotype Nintedanib Capsules is indicated for the treatment of adults with chronic fibrosing interstitial lung diseases (ILDs) with a...
Common Doses
- 150 mg
- 100 mg
- 300 mg
Dosage
2 DOSAGE AND ADMINISTRATION Recommended dosage: 150 mg taken orally twice daily approximately 12 hours apart taken with food. ( 2.2 ) Recommended dosage in patients with mild hepatic impairment (Child Pugh A): 100 mg taken orally twice daily approximately 12 hours apart taken with food. ( 2.3 , 8.6 ) Consider temporary dose reduction to 100 mg, treatment interruption, or discontinuation for management of adverse reactions. ( 2.4 , 5.2 , 5.3 , 6 ) Prior to treatment initiation, conduct liver function tests in all patients and a pregnancy test in females of reproductive potential. ( 2.1 , 5.
Contraindications
- 4 CONTRAINDICATIONS None None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Elevated Liver Enzymes and Drug-Induced Liver Injury [see Warnings and Precautions (5.2) ] Gastrointestinal Disorders [see Warnings and Precautions (5.3) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.4) ] Arterial Thromboembolic Events [see Warnings and Precautions (5.5) ] Risk of Bleeding [see Warnings and Precautions (5.6) ] Gastrointestinal Perforation [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. Monitor patients closely for tolerability of Nintedanib Capsules. ( 7.1 ) 7.1 P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 [see Clinical Pharmacology (12.3) ] . Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of P-gp and CYP3A4 inhibitors (e.g.