What are the precautions for ibrutinib/ibrutinib?

In the clinical studies of ibrutinib/ibrutinib, warnings and precautions such as bleeding, infection, arrhythmia, heart failure and sudden death, hypertension, cytopenia, second primary malignant tumors, tumor lysis syndrome, embryo-fetal toxicity have appeared. Discontinue and resume at reduced dose upon recovery, or permanently discontinue based on severity.

1. Bleeding: Patients receiving treatment experienced fatal bleeding events. Major bleeding (≥Grade 3, severe, or any central nervous system event; such as intracranial hemorrhage (including subdural hematoma), gastrointestinal bleeding, hematuria, and postoperative bleeding), the mechanism of the bleeding event is unknown. Concomitant use of anticoagulants or antiplatelets with ibrutinib may increase the risk of major bleeding. Consider the risks and benefits of anticoagulant or antiplatelet therapy when used with ibrutinib. Monitor for signs and symptoms of bleeding. Consider the benefits-risks of discontinuing ibrutinib for at least 3 to 7 days before and after surgery, depending on the type of surgery and bleeding risk.

2. Infection: Treat fatal and non-fatal infections (including bacterial, viral or fungal infections). Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jiroveci pneumonia (PJP) have occurred in patients receiving ibrutinib. Consider prophylaxis according to standard of care in patients at increased risk for opportunistic infections. Monitor and evaluate patients for fever and infection and treat appropriately.

3. Arrhythmias, heart failure, and sudden death: These events occur particularly in patients with cardiac risk factors (including hypertension and diabetes, previous history of arrhythmias) and in patients with acute infections. Assess cardiac history and function at baseline, and monitor patients for arrhythmias and cardiac function. For patients who develop arrhythmic symptoms (e.g., palpitations, dizziness, syncope, chest pain), new-onset dyspnea, or other cardiovascular problems, obtain further evaluation (e.g., electrocardiogram, echocardiogram) as needed. Manage arrhythmias and heart failure appropriately, follow dose adjustment guidelines, and consider the risks and benefits of continuing ibrutinib therapy.

4. Hypertension: In a 5-year long-term safety analysis, more than 1,000 patients with B-cell malignancies were treated for a median of 36 months, and the cumulative rate of hypertension increased over time. Monitor blood pressure in patients receiving ibrutinib, initiate or adjust antihypertensive medications as appropriate throughout treatment, and follow dose adjustment guidelines for grade 3 or higher hypertension.

5. Cytopenia: Cytopenia will occur in clinical studies. During drug treatment, patients should monitor complete blood cell count monthly.

6. Second primary malignancies: Among patients treated in clinical trials, other malignancies developed (10%), including non-skin cancers (3.9%); the most common second primary malignancy was non-melanoma skin cancer (6%).

7. Tumor lysis syndrome: Tumor lysis syndrome rarely occurs with ibrutinib. Assess baseline risks (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

8. Embryo-Fetal toxicity: According to animal studies, ibrutinib taken by pregnant women can cause harm to the fetus. Administration of ibrutinib to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity, including malformations upon exposure that were 3-20 times greater than those reported in patients with hematological malignancies. Inform pregnant women of potential risks to the fetus. Advise females of childbearing potential to use effective contraception during treatment and for 1 month after the last dose.