Brigatinib/Brigatinib (Embry) official instructions and medication instructions

1. Overview of Drugs

Brigatinib (Brigatinib, trade name: Alunbrig or Ambry) is an oral small molecule tyrosine kinase inhibitor (TKI) used for the targeted treatment of advanced non-small cell lung cancer (NSCLC) with specific genetic alterations. Brigatinib has shown inhibitory effects on multiple kinases in vitro and in vivo, including anaplastic lymphoma kinase (ALK), ROS1, insulin-like growth factor-1 receptor (IGF-1R), FLT3, and partial EGFR deletion and point mutation forms. Its anti-tumor effect is achieved by blocking ALK and downstream signaling pathways (STAT3, AKT, ERK1/2 and S6 phosphorylation), thereby inhibiting tumor cell proliferation and showing significant dose-dependent inhibitory effects in animal models.

2. Indications

Brigatinib is mainly used to treat adult patients with metastatic non-small cell lung cancer who are ALK-positive as tested byFDA-approved tests. After confirming the ALK-positive status through companion diagnostics, doctors can choose brigatinib as a targeted therapy for the patient. Brigatinib provides a new treatment option for patients who cannot tolerate or respond to first-line ALK inhibitor therapy.

3. Usage and dosage

1. Initial administration: The patient'sALK positive status should be confirmed before treatment. The recommended dose is 90 mg orally once daily for the first 7 days, and then increased to 180 mg once daily until disease progression or intolerable toxicity occurs. The medicine can be taken with food or on an empty stomach. It should be swallowed whole and should not be crushed or chewed. If a dose is missed or vomiting occurs, the dose should not be taken again and the next dose should be continued as originally planned.

2. Dose adjustment: If adverse reactions occur, the dose can be adjusted according to tolerance: The 90mg dose can be reduced to 60mg, and the 180mg dose can be adjusted in descending steps of 120mg→90mg→60mg. If the interruption exceeds 14 days due to reasons other than adverse reactions, treatment should be resumed starting at 90 mg and continued for 7 days before returning to the previously tolerated dose.

3. Drug interactions: When using strong or moderateCYP3A inhibitors, the brigatinib dose should be reduced by approximately 50%; when using moderate CYP3A inducers, the current tolerated dose can be maintained for 7 days and then gradually increased until the original dose is restored.

4. Dose adjustment for special groups: Patients with severe hepatic impairment (Child-Pugh C) or severe renal insufficiency (creatinine clearance 15-29 mL/min) should reduce the daily dose of brigatinib by approximately 40%.

4. Adverse reactions

Clinical studies have shown that common adverse reactions include hyperglycemia, hyperinsulinemia, anemia, leukopenia, nausea, diarrhea, fatigue, cough, headache, hypophosphatemia, rash, vomiting, dyspnea and hypertension. Laboratory tests may show elevated liver function indicators (ALT, AST), elevated pancreatic enzymes (amylase, lipase), elevated creatine kinase, or abnormal blood coagulation (elevated APTT).

5. Storage

Brigatinib is supplied in tablet form and should be stored at a controlled room temperature of 20°C to 25°C (68°F to 77°F), with an allowable temperature range of 15°C to 30°C. Medications should be protected from moisture and high temperatures, and kept out of the reach of children.

6. Mechanism of action

Brigatinib achieves the inhibitory effect on tumor cells by irreversibly inhibitingALK tyrosine kinase and its downstream signaling pathways. In in vitro experiments, it can inhibit the proliferation of cells expressing EML4-ALK and NPM-ALK fusion proteins, and shows anti-tumor activity against a variety of ALK mutant forms, including crizotinib-resistant mutations. In a mouse intracranial tumor model, brigatinib can significantly reduce tumor burden and prolong survival, showing strong clinical potential.

Reference materials:https://www.alunbrig.com/