OFEV- nintedanib capsule
Boehringer Ingelheim Pharmaceuticals, Inc. (10368.00, 9969)
1 INDICATIONS AND USAGE
OFEV is indicated for the treatment of idiopathic pulmonary fibrosis (IPF).
2 DOSAGE AND ADMINISTRATION
2.1 Testing Prior to OFEV Administration
Conduct liver function tests and a pregnancy test prior to initiating treatment with OFEV [see Warnings and Precautions (5.2, 5.4)].
2.2 Recommended Dosage
The recommended dosage of OFEV is 150 mg twice daily administered approximately 12 hours apart.
OFEV capsules should be taken with food [see Clinical Pharmacology (12.3)] and swallowed whole with liquid. OFEV capsules should not be chewed or crushed because of a bitter taste. The effect of chewing or crushing of the capsule on the pharmacokinetics of nintedanib is not known.
If a dose of OFEV is missed, the next dose should be taken at the next scheduled time. Advise the patient to not make up for a missed dose. Do not exceed the recommended maximum daily dosage of 300 mg.
In patients with mild hepatic impairment (Child Pugh A), the recommended dosage of OFEV is 100 mg twice daily approximately 12 hours apart taken with food.
2.3 Dosage Modification due to Adverse Reactions
In addition to symptomatic treatment, if applicable, the management of adverse reactions of OFEV may require dose reduction or temporary interruption until the specific adverse reaction resolves to levels that allow continuation of therapy. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If a patient does not tolerate 100 mg twice daily, discontinue treatment with OFEV [see Warnings and Precautions (5.2, 5.3, 5.5, 5.7) and Adverse Reactions (6.1)].
DOSAGE FORMS AND STRENGTHS
150 mg capsules: brown, opaque, oblong, soft capsules imprinted in black with the Boehringer Ingelheim company symbol and "150″.
100 mg capsules: peach, opaque, oblong, soft capsules imprinted in black with the Boehringer Ingelheim company symbol and "100″.
OFEV capsules contain nintedanib, a kinase inhibitor [see Mechanism of Action (12.1)]. Nintedanib is presented as the ethanesulfonate salt (esylate), with the chemical name 1H -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).
Its structural formula is:
Nintedanib esylate is a bright yellow powder with an empirical formula of C31 H33 N5 O4 ĚC2 H6 O3 S and a molecular weight of 649.76 g/mol.
OFEV capsules for oral administration are available in 2 dose strengths containing 100 mg or 150 mg of nintedanib (equivalent to 120.40 mg or 180.60 mg nintedanib ethanesulfonate, respectively). The inactive ingredients of OFEV are the following: Fill Material: triglycerides, hard fat, lecithin. Capsule Shell: gelatin, glycerol, titanium dioxide, red ferric oxide, yellow ferric oxide, black ink.
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, and Fms-like tyrosine kinase-3 (FLT3). Among them, FGFR, PDGFR, and VEGFR have been implicated in IPF pathogenesis. Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts representing essential mechanisms of the IPF pathology. In addition, nintedanib inhibits the following nRTKs: Lck, Lyn and Src kinases. The contribution of FLT3 and nRTK inhibition to IPF efficacy is unknown.