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 metastatic non-small cell lung cancer (NSCLC) who have not received prior ALK inhibitor therapy or who have disease progression on or intolerant to crizotinib.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Can be taken with or without food.
Recommended Dosage (Two-Part Dosing):
Part 1: 90 mg once daily for the first 7 days.
Part 2: If the 90 mg dose is tolerated, increase the dose to 180 mg once daily starting on Day 8.
Rationale: The initial 7-day lead-in period is intended to monitor for initial adverse reactions (especially pulmonary toxicity) before reaching the full therapeutic dose.
Missed Dose/Vomiting:
If a dose is missed or vomiting occurs, do not retake the dose; take the next scheduled dose at the regular time.
3. Mechanism of Action
ALK Inhibition:
Brigatinib is a potent inhibitor of wild-type ALK and mutant ALK proteins (including crizotinib-resistant mutations).
Tumor Growth Inhibition:
It inhibits the phosphorylation of ALK and downstream signaling proteins (such as STAT3, AKT, and ERK), thereby blocking cell proliferation and inducing apoptosis in ALK-expressing tumor cells.
4. Safety and Warnings
Pulmonary Toxicity (Pneumonitis/ILD):
Non-infectious pneumonia and Interstitial Lung Disease (ILD) can occur, typically within the first week of treatment. Monitor patients for pulmonary symptoms (cough, dyspnea, hypoxia). Discontinue or interrupt treatment if severe.
Hypertension:
Hypertension can occur early during treatment. Monitor blood pressure weekly for the first month and as clinically indicated.
Bradycardia:
Can cause bradycardia and heart block. Monitor heart rate and blood pressure, especially in patients taking medications known to cause bradycardia.
Creatine Kinase (CPK) Elevation:
Asymptomatic increases in CPK can occur. Monitor CPK levels prior to initiation and periodically during treatment.
Pancreatic Enzyme Elevations:
Increases in amylase and lipase can occur. Monitor serum amylase and lipase levels.
5. Adverse Reactions
Most Common:
General: Nausea, diarrhea, diarrhea, fatigue, rash, cough, dyspnea.
Laboratory Abnormalities: Increased CPK, increased ALT/AST, increased amylase/lipase, hypertension.
6. Drug Interactions
CYP3A Substrate:
Brigatinib is metabolized by CYP3A.
Strong CYP3A Inhibitors (e.g., Clarithromycin, Ketoconazole): Avoid co-administration. If unavoidable, reduce the Brigatinib dose.
Strong CYP3A Inducers (e.g., Rifampin, Phenobarbital): Avoid co-administration as they significantly decrease Brigatinib exposure, leading to potential treatment failure.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Brigatinib.
Appearance: Yellow, oval, film-coated tablets (90 mg and 180 mg strengths available).
Storage: Store at 20°C–25°C (68°F–77°F).