Brensocatib Medication Guide: DPP1 Inhibitor Indications and Safe Use Specifications

　　Brensocatib is an oral dipeptidyl peptidase-1(DPP1)inhibitor clinically used for neutrophil-mediated inflammatory conditions,including non-cystic fibrosis bronchiectasis(NCFB).It exerts its therapeutic effect by inhibiting the activation of neutrophil serine proteases(such as neutrophil elastase and proteinase 3),thereby reducing airway inflammation and tissue damage and slowing disease progression.

　　Pre-Treatment Precautions

　　Comprehensive baseline assessments are required prior to initiating brensocatib therapy to ensure patient safety.First,active infections must be ruled out,with particular attention to respiratory tract infections and fungal infections;treatment should not be initiated until active infection is resolved.Second,screening for latent tuberculosis infection is mandatory;patients with positive results should complete standard prophylactic anti-tuberculosis therapy before starting brensocatib.Baseline liver function tests,including alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin,must also be obtained.For patients of childbearing potential,a negative pregnancy test is required before treatment,and effective contraception must be used throughout the therapeutic course.

　　Monitoring During Treatment

　　Regular monitoring focusing on infection status,liver function and hematological parameters is required during therapy.For infection monitoring,patients should be evaluated every 2 to 4 weeks for new-onset fever,worsening cough,increased sputum production,dyspnea and other symptoms,with periodic testing of complete blood count,C-reactive protein and procalcitonin.Brensocatib should be temporarily discontinued in the event of severe infection requiring systemic antibiotic or antifungal therapy.Liver function should be monitored monthly for the first 3 months of treatment,and every 3 months thereafter.Treatment should be discontinued if ALT levels exceed 5 times the upper limit of normal.Hematological monitoring with monthly complete blood count is required to track neutrophil count;therapy should be suspended if neutrophil count falls below 1.0×10^9/L,and subsequent dosing should be reassessed.

　　Drug Interactions

　　Brensocatib is primarily metabolized by the CYP2D6 and CYP3A4 enzymes.Concomitant use with strong CYP2D6 inhibitors(such as paroxetine and fluoxetine)should be avoided,as these agents can increase brensocatib plasma concentrations and elevate the risk of adverse reactions.Interactions between brensocatib and CYP3A4 inhibitors or inducers are mild and not clinically significant,so no routine dose adjustment is required for concomitant use.

　　Use in Special Populations

　　For patients with renal impairment,no dose adjustment is needed in those with mild renal impairment(creatinine clearance≥60 mL/min).Data on use in patients with moderate to severe renal impairment(creatinine clearance<60 mL/min)are limited,and administration requires careful benefit-risk assessment.For patients with hepatic impairment,use is not recommended in those with moderate to severe hepatic impairment(Child-Pugh Class B/C).The safety and efficacy of brensocatib in pediatric patients under 12 years of age have not been established,and routine use is not recommended.