Alunbrig Brigatinib Tablets

1. Indications and Usage
ALK-Positive Non-Small Cell Lung Cancer (NSCLC):
Indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.
Approval Context:
Previously treated patients (post-crizotinib).
Treatment-naive patients (first-line therapy).
2. Dosage and Administration
Recommended Dosage:
First-Line Therapy: 90 mg orally once daily for the first 7 days; if tolerated, increase to the recommended dose of 180 mg once daily thereafter.
Post-Crizotinib Therapy: 180 mg orally once daily.
Administration Instructions:
Administer orally with or without food.
Swallow tablets whole; do not crush, chew, or break.
Dose Modifications:
Dose reductions (to 120 mg, 90 mg, or 60 mg once daily) are recommended based on individual safety and tolerability (e.g., for hypertension, CPK elevation, or pulmonary toxicity).
If the 180 mg dose is not tolerated, reduce to 120 mg; if 90 mg is not tolerated, reduce to 60 mg.
3. Mechanism of Action
ALK Tyrosine Kinase Inhibitor:
Brigatinib is a kinase inhibitor of ALK, ROS1, and EGFR.
Physiological Effect:
It inhibits ALK-mediated phosphorylation of downstream signaling proteins (STAT3, AKT, ERK1/2, S6) in cells expressing ALK fusion proteins (e.g., EML4-ALK).
It exhibits potent anti-tumor activity against ALK mutations associated with resistance to crizotinib and demonstrates efficacy in reducing intracranial tumor burden.
4. Safety and Warnings
Interstitial Lung Disease (ILD)/Pneumonitis:
Severe and fatal cases have been reported. Monitor for pulmonary symptoms (cough, dyspnea, hypoxia), especially during the first week of treatment. Withhold or discontinue based on severity.
Hypertension:
Occurs in a significant percentage of patients. Monitor blood pressure 2 weeks after initiation and at least monthly thereafter.
Bradycardia:
Monitor heart rate and blood pressure regularly.
Elevated Creatine Phosphokinase (CPK):
Monitor CPK levels regularly. Withhold for unexplained CPK elevation.
Pancreatic Enzyme Elevations:
Monitor serum lipase and amylase levels regularly.
Hyperglycemia:
Assess fasting serum glucose prior to initiation and periodically thereafter.
Visual Disturbances:
Can occur. Withhold for moderate/severe symptoms and evaluate ophthalmologically.
Embryo-Fetal Toxicity:
Can cause fetal harm. Advise females of reproductive potential to use effective contraception.
5. Adverse Reactions
Most Common:
Hypertension, increased CPK, diarrhea, rash, fatigue, increased lipase, cough, increased amylase, nausea, increased glucose, headache.
6. Drug Interactions
CYP3A Inhibitors:
Concomitant use with strong CYP3A inhibitors increases brigatinib exposure. Avoid concomitant use; if unavoidable, reduce the brigatinib dose.
CYP3A Inducers:
Concomitant use with strong CYP3A inducers significantly decreases brigatinib exposure. Avoid concomitant use.
P-gp Substrates:
Brigatinib is a P-gp inhibitor. Avoid co-administration of drugs with a narrow therapeutic index that are P-gp substrates.
7. Pharmaceutical Information
Chemical Name:
5-[(2-Isopropyl-5-m-tolyl-1H-imidazol-4-yl)methoxy]-2-(2-morpholinoethoxy)aniline.
Storage:
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).