Brigatinib

Brand Names: Alunbrig

Drug Class: Kinase Inhibitor

Overview

11 DESCRIPTION Brigatinib is a kinase inhibitor. The chemical name for brigatinib is 5-chloro-N 4 -[2-(dimethylphosphoryl)phenyl]-N 2 -{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}pyrimidine-2,4-diamine. The molecular formula is C 29 H 39 ClN 7 O 2 P which corresponds to a formula weight of 584.10 g/mol. Brigatinib has no chiral centers.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Brigatinib is a tyrosine kinase inhibitor (TKI) with in vitro activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib inhibited autophosphorylation of ALK and ALK-mediated phosphorylation of the downstream signaling proteins STAT3, AKT, ERK1/2, and S6 in in vitro and in vivo assays. Brigatinib also inhibited the in vitro proliferation of cell lines expressing EML4-ALK and NPM-ALK fusion proteins and demonstrated dose-dependent inhibition of EML4-ALK-positive NSCLC xenograft growth in mice.

Indications

  • 1 INDICATIONS AND USAGE ALUNBRIG is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test [see Dosage and Administration (2.1) ] . ALUNBRIG is a kinase inhibitor indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. ( 1 , 2.1 )

Common Doses

  • 90 mg
  • 180 mg
  • 60 mg
  • 120 mg

Dosage

2 DOSAGE AND ADMINISTRATION 90 mg orally once daily for the first 7 days; then increase to 180 mg orally once daily. May be taken with or without food. ( 2.2 ) 2.1 Patient Selection Select patients for the treatment of metastatic NSCLC with ALUNBRIG based on the presence of ALK positivity in tumor specimens [see Clinical Studies (14) ] . Information on FDA-approved tests for the detection of ALK rearrangements in NSCLC is available at http://www.fda.gov/CompanionDiagnostics. 2.

Contraindications

  • 4 CONTRAINDICATIONS None. None. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the prescribing information: Interstitial Lung Disease (ILD)/Pneumonitis [see Warnings and Precautions (5.1) ] Hypertension [see Warnings and Precautions (5.2) ] Bradycardia [see Warnings and Precautions (5.3) ] Visual Disturbance [see Warnings and Precautions (5.4) ] Creatine Phosphokinase (CPK) Elevation [see Warnings and Precautions (5.5) ] Pancreatic Enzymes Elevation [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.

Interactions

  • 7 DRUG INTERACTIONS CYP3A Inhibitors : Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inhibitors. If coadministration of a strong or moderate CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG. ( 2.4 , 7.1 ) CYP3A Inducers : Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inducers. If coadministration of a moderate CYP3A inducer is unavoidable, increase the dose of ALUNBRIG. ( 2.5 , 7.1 ) 7.