Imbruvica Special Precautions

Bleeding-related events: There have been reports of bleeding events in patients treated with Ibrutinib (Imbruvica), both with and without thrombocytopenia. These include minor bleeding events such as contusion, epistaxis, and petechiae; and major bleeding events, some fatal, including gastrointestinal bleeding, intracranial hemorrhage, and hematuria.
In an in vitro platelet function study, inhibitory effects of ibrutinib on collagen-induced platelet aggregation were observed (See Pharmacology: Pharmacodynamics under Actions). Use of either anticoagulant or antiplatelet agents concomitantly with Ibrutinib (Imbruvica) increases the risk of major bleeding. A higher risk for major bleeding was observed with anticoagulant than with antiplatelet agents. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with Ibrutinib (Imbruvica). Monitor for signs and symptoms of bleeding.
Supplements such as fish oil and vitamin E preparations should be avoided.
Ibrutinib (Imbruvica) should be held at least 3 to 7 days pre- and post‑surgery depending upon the type of surgery and the risk of bleeding.
Patients with congenital bleeding diathesis have not been studied.
Leukostasis: There were isolated cases of leukostasis reported in patients treated with Ibrutinib (Imbruvica). A high number of circulating lymphocytes (>400,000/mcL) may confer increased risk. Consider temporarily holding Ibrutinib (Imbruvica). Patients should be closely monitored. Administer supportive care including hydration and/or cytoreduction as indicated.
Infections: Infections (including sepsis, neutropenic sepsis, bacterial, viral, or fungal infections) were observed in patients treated with Ibrutinib (Imbruvica). Some of these infections have been associated with hospitalization and death. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Although causality has not been established, cases of progressive multifocal leukoencephalopathy (PML) and hepatitis B reactivation have occurred in patients treated with Ibrutinib (Imbruvica). Cases of hepatitis E, which may be chronic, have occurred in patients treated with Ibrutinib (Imbruvica). Patients should be monitored for signs and symptoms (fever, chills, weakness, confusion, vomiting, jaundice and abnormal liver function tests) and appropriate therapy should be instituted as indicated.
Cytopenias: Treatment‑emergent Grade 3 or 4 cytopenias (neutropenia, thrombocytopenia and anemia) were reported in patients treated with Ibrutinib (Imbruvica). Monitor complete blood counts monthly.
Interstitial lung disease (ILD): Cases of ILD have been reported in patients treated with Ibrutinib (Imbruvica). Monitor patients for pulmonary symptoms indicative of ILD. If symptoms develop, interrupt Ibrutinib (Imbruvica) and manage ILD appropriately. If symptoms persist, consider the risks and benefits of Ibrutinib (Imbruvica) treatment and follow the dose modification guidelines.
Cardiac arrhythmias and cardiac failure: Fatal and serious cardiac arrhythmias or cardiac failure have occurred in patients treated with Ibrutinib (Imbruvica). Patients with significant cardiac co-morbidities may be at greater risk of events, including sudden fatal cardiac events. Atrial fibrillation, atrial flutter, ventricular tachyarrhythmia and cardiac failure have been reported, particularly in patients with acute infections, or cardiac risk factors including hypertension, diabetes mellitus, and a previous history of cardiac arrhythmia.
Appropriate clinical evaluation of cardiac history and function should be performed prior to initiating Ibrutinib (Imbruvica). Patients should be carefully monitored during treatment for signs of clinical deterioration of cardiac function and clinically managed. Consider further evaluation (e.g., ECG, echocardiogram), as indicated for patients in whom there are cardiovascular concerns. For signs and symptoms that persist, consider the risks and benefits of Ibrutinib (Imbruvica) treatment and follow the dose modification guidelines.
Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported with Ibrutinib (Imbruvica) therapy. Patients at risk of tumor lysis syndrome are those with high tumor burden prior to treatment. Monitor patients closely and take appropriate precautions.
Non-melanoma skin cancer: Non‑melanoma skin cancers have occurred in patients treated with Ibrutinib (Imbruvica). Monitor patients for the appearance of non‑melanoma skin cancer.
Hypertension: Hypertension has occurred in patients treated with Ibrutinib (Imbruvica). Regularly monitor blood pressure in patients treated with Ibrutinib (Imbruvica) and initiate or adjust antihypertensive medication throughout treatment with Ibrutinib (Imbruvica) as appropriate.
Effects on Ability to Drive and Use Machines: Fatigue, dizziness and asthenia have been reported in some patients taking Ibrutinib (Imbruvica) and should be considered when assessing a patient's ability to drive or operate machines.