Non–small cell lung cancer, metastatic

Antineoplastic Agent
Brigatinib is a tyrosine kinase inhibitor, and has shown activity against multiple kinases (eg, ALK, ROS1, insulin-like growth factor-1 receptor, and FLT-3), EGFR deletions, and point mutations at clinically achievable concentrations.

1.Distribution: 307 L.
2.Protein binding: 91% bound to plasma proteins (not concentration dependent).
3.Metabolism: Primarily hepatic via CYP2C8 and CYP3A4; N-demethylation and cysteine conjugation are the two major metabolic pathways.
4.Half-life elimination: 25 hours.
5.Excretion: Feces (65%; 41% as unchanged drug); urine (25%; 86% as unchanged drug).

Hypersensitivity to brigatinib or any component of the formulation.

Fetal risk may occur when used during pregnancy.

Infant risk cannot be ruled out.

Elevated aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT), elevated creatine phosphokinase (CPK), hyperglycemia, elevated lipase, hyperinsulinemia, diarrhea, elevated amylase, anemia, nausea, fatigue, hypophosphatemia, lymphopenia, cough, elevated alkaline phosphatase, rash, prolonged activated partial thromboplastin time (APTT), myalgia, headache, hypertension, leukopenia, dyspnea, and vomiting.

90 mg once daily for 7 days; if tolerated, then increase dose to 180 mg once daily; continue until disease progression or unacceptable toxicity.

CrCl 30 to 89 mL/minute: No dosage adjustment is necessary.
CrCl 15 to 29 mL/minute: Reduce dose by ~50% (eg, from 180 mg once daily to 90 mg once daily, from 90 mg once daily to 60 mg once daily).

Hepatic impairment prior to treatment initiation:
Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment is necessary.
Severe impairment (Child-Pugh class C): Reduce dose by ~40% (eg, from 180 mg once daily to 120 mg once daily, from 120 mg once daily to 90 mg once daily, from 90 mg once daily to 60 mg once daily).