What are the precautions for Brigatinib/Brigatinib?

In clinical studies of Brigatinib/Brigatinib, interstitial lung disease/pneumonia occurred pan>, hypertension, bradycardia, visual impairment, elevated creatine phosphokinase, elevated pancreatic enzyme, hepatotoxicity, hyperglycemia, photosensitivity, embryo-fetal toxicity and other warnings and precautions. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Interstitial lung disease (ILD)/pneumonitis: Serious, life-threatening and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with brigatinib. Monitor for new or worsening respiratory symptoms (e.g., dyspnea, cough, etc.), especially during the first week of initiating brigatinib. Discontinue brigatinib and promptly evaluateILD/pneumonitis or other causes of respiratory symptoms in any patient who develops new or worsening respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia).

2. Hypertension: Control blood pressure before treatment with brigatinib. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with brigatinib. Brigatinib should be discontinued in patients with grade 3 hypertension despite optimal antihypertensive therapy. After resolution or improvement to Grade 1, resume brigatinib at the same dose. Consider permanently discontinuing brigatinib therapy for grade 4 hypertension or recurrence of grade 3 hypertension. Use caution when coadministering brigatinib with antihypertensive agents that cause bradycardia.

3. Bradycardia: During treatment with brigatinib, monitor heart rate and blood pressure. If concomitant use of drugs known to cause bradycardia cannot be avoided, the patient should be monitored more frequently. For symptomatic bradycardia, discontinue brigatinib and review concomitant medications known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or adjusted, continue brigatinib at the same dose after resolution of symptomatic bradycardia; otherwise, reduce the dose of brigatinib after resolution of symptomatic bradycardia. If no life-threatening concomitant medications are identified, discontinue brigatinib therapy.

4. Visual impairment: including blurred vision, photophobia, diplopia and reduced visual acuity, light perception and visual acuity , patients are advised to report any visual symptoms. Discontinue brigatinib and obtain an ophthalmological evaluation in patients who develop new or worsening visual symptoms of grade 2 or worse. Resume brigatinib at a reduced dose when Grade 2 or 3 visual impairment returns to Grade 1 severity or baseline. Permanently discontinue brigatinib Treatment grade 4 visual impairment.

5. Elevated creatine phosphokinase (CPK): Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitoring during brigatinib treatmentCPK level. For grade 3 or 4 CPK elevations associated with grade 2 or higher muscle pain or weakness, brigatinib should be discontinued.

6. Elevated pancreatic enzymes: Monitor lipase and amylase during patient treatment with brigatinib. For grade 3 or 4 pancreatic enzyme elevations, discontinue brigatinib.

7. Hepatotoxicity: including increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), and severe liver cell damage adverse reactions. Therefore, during brigatinib treatment, especially in the first 3 months, AST, ALT and total bilirubin should be monitored. For grade 3 or 4 liver enzyme elevations with bilirubin ≤2 × ULN, brigatinib should be discontinued. Upon resolution or return to grade 1 or less (≤3 × ULN) or baseline, resume brigatinib at the next lower dose. In the absence of cholestasis or hemolysis, brigatinib should be permanently discontinued in patients with grade 2-4 liver enzyme elevations and total bilirubin elevations greater than THAN 2 times.

8. Hyperglycemia: Assess fasting blood glucose before starting brigatinib and monitor regularly thereafter. Initiate or optimize antihyperglycemic medications as needed. If hyperglycemia cannot be adequately controlled with optimal medical therapy, brigatinib should be discontinued until adequate glycemic control is achieved.

9. Photosensitivity: It is recommended that patients limit sun exposure while taking brigatinib and for at least 5 days after stopping the drug. Patients are advised to wear a hat and protective clothing when outdoors and use broad-spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and lip balm (SPF ≥ 30) to help prevent sunburn.

10. Embryo-fetal toxicity: Based on its mechanism of action and findings in animals, brigatinib can cause fetal damage when administered to pregnant women. Administration of brigatinib to pregnant rats during organogenesis resulted in dose-related skeletal abnormalities at doses as low as 12.5 mg/kg/day (AUC of 180 mg once daily, approximately 0.7 times the human exposure) and increased postimplantation loss, malformations, and decreased fetal weight at doses of 25 mg/kg/day (approximately 180 mg once daily, approximately 1.26 times the human exposure) or higher.

Inform women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with brigatinib and for at least 4 months after the last dose. Advise men who are partners of a female of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose.