What are the precautions for taking Zanubrutinib?

During treatment with Zanubrutinib, patients should pay attention to the occurrence of bleeding, infection, cytopenia, second primary malignant tumor, arrhythmia, embryo-fetal toxicity and other events.

1. Hemorrhage: In clinical trials, Grade 3 or higher bleeding, including intracranial and gastrointestinal bleeding, hematuria, and hemothorax, was reported in 3.6% of patients receiving zanubrutinib monotherapy, and 0.3% of patients died. Bleeding of any degree, excluding purpura and petechiae, occurred in 30% of patients. Bleeding occurs in patients with or without antiplatelet or anticoagulant therapy. The combination of zanubrutinib and antiplatelet or anticoagulant drugs may further increase the risk of bleeding. Monitor for signs and symptoms of bleeding and discontinue zanubrutinib if any degree of intracranial bleeding occurs. Depending on the type of surgery and risk of bleeding, consider discontinuing zanubrutinib for 3 to 7 days before or after surgery.

2. Infection: Fatal and serious infections (including bacterial, viral or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies who received zanubrutinib monotherapy. Consider prophylaxis against herpes simplex virus, Pneumocystis pneumonia, and other infections, monitor and evaluate patients for fever or other signs and symptoms of infection, and treat appropriately, according to the standard of care for patients at increased risk for infection.

3. Cytopenia: Based on laboratory measurements, patients receiving zanubrutinib monotherapy developed grade 3 or 4 cytopenias, including neutropenia, thrombocytopenia, and anemia. Grade 4 neutropenia occurred in 11% of patients and grade 4 thrombocytopenia in 2.8% of patients. Monitor complete blood counts periodically during treatment and interrupt treatment, reduce dose, or discontinue treatment as needed. Treatment is with growth factors or blood transfusions as needed.

4. Second primary malignant tumors: including non-skin cancer, occurred in 13% of patients treated with zanubrutinib monotherapy. The most common second primary malignancy is non-melanoma skin cancer, reported in 7% of patients. Other second primary malignancies include malignant solid tumors, melanoma, and hematologic malignancies. The patient is advised to use sunscreen and the patient is monitored for the development of a second primary malignancy.

5. Arrhythmia: In clinical studies, 3.7% of patients who received zanubrutinib monotherapy reported atrial fibrillation and atrial flutter, of which 1.7% had grade 3 or above cases. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher ventricular arrhythmias were reported in 0.2% of patients. Monitor for signs and symptoms of cardiac arrhythmias (e.g., palpitations, dizziness, syncope, dyspnea, chest discomfort) and treat appropriately.

6. Embryo-Fetal Toxicity: Based on animal studies, zanubrutinib can cause harm to the fetus when taken by pregnant women. Administration of zanubrutinib to pregnant rats during organogenesis resulted in embryo-fetal toxicity, including malformations 5 times reported in patients exposed to the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking zanubrutinib and for 1 week after the last dose. Advise men to avoid childbearing during treatment and for 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential harm to the fetus.