What are the precautions for Fam-trastuzumab deruxtecan-nxki?

During clinical studies of Fam-trastuzumab deruxtecan-nxki , warnings and precautions such as interstitial lung disease/pneumonitis, neutropenia, left ventricular dysfunction, embryo-fetal toxicity, etc. may occur.

1. Interstitial lung disease (ILD)/pneumonitis: Trastuzumab may cause severe, life-threatening or fatal interstitial lung disease (ILD), including pneumonia. Advise patients to immediately report cough, difficulty breathing, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Investigate evidence of ILD promptly. Evaluate patients with suspected ILD by radiologic imaging. Consider consulting a doctor. For asymptomatic (grade 1) ILD, consider corticosteroid therapy (eg, ≥0.5 mg/kg/day prednisone or equivalent). Stop taking the medicine until recovery occurs. If symptomatic ILD (grade 2 or greater) occurs, initiate systemic corticosteroid therapy (e.g., ≥1 mg/kg/day prednisone or equivalent) immediately and continue for at least 14 days, then taper for at least 4 weeks. For patients diagnosed with symptomatic (grade 2 or above) ILD, permanently discontinue trastuzumab.

2. Neutropenia: including febrile neutropenia. Monitor complete blood counts before initiating trastuzumab and before each dose, and as clinically indicated. Depending on the severity of neutropenia, dose interruption or reduction of trastuzumab may be required.

3. Left ventricular dysfunction: The risk of developing left ventricular dysfunction may be increased, and a decrease in left ventricular ejection fraction (LVEF) has been observed in anti-HER2 treatments including trastuzumab. AssessLVEF prior to initiatingtrastuzumaband periodically during treatment as clinically indicated. Reduce LVEF by interrupting treatment. Permanently discontinue trastuzumab if LVEF falls below 40% or if the absolute decrease from baseline is greater than 20%. Permanently discontinue trastuzumab in patients with symptomatic congestive heart failure (CHF). Treatment with trastuzumab has not been studied in patients who had a history of clinically significant heart disease or whose LVEF was less than 50% before starting treatment.

4. Embryo-fetal toxicity: According to its mechanism of action, trastuzumab will cause harm to the fetus when administered to pregnant women. In postmarketing reports, use of HER2-directed antibodies during pregnancy resulted in oligohydramnios, manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Based on its mechanism of action, DXd, the topoisomerase inhibitor component of trastuzumab, can also cause harm to the embryo when administered to pregnant women because it is genotoxic and targets actively dividing cells. Inform patients of the potential risks to the fetus.

Before starting trastuzumabPreviously, verify the pregnancy status of females of reproductive potential. Advise females of childbearing potential to use effective contraception during treatment and for 7 months after the last dose. Advise male patients with female partners of childbearing potential to use effective contraception during treatment and for 4 months after the last dose.