Management of adverse effects/toxicity of ibrutinib

• Published in: Critical reviews in oncology/hematology Vol. 136; pp. 56 - 63
• Main Author: Paydas, Semra
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2019
• Subjects: Adverse effect; Agammaglobulinaemia Tyrosine Kinase - antagonists & inhibitors; Atrial fibrillation; Atrial Fibrillation - chemically induced; Atrial Fibrillation - epidemiology; Atrial Fibrillation - therapy; Bruising; Diarrhea; Drug-Related Side Effects and Adverse Reactions - epidemiology; Drug-Related Side Effects and Adverse Reactions - therapy; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Hemorrhage - therapy; Humans; Ibrutinib; Incidence; Infection; Leukemia - drug therapy; Leukemia - epidemiology; Lymphoma - drug therapy; Lymphoma - epidemiology; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Skin reactions; Infection; Atrial fibrillation; Diarrhea; Bruising; Skin reactions; Adverse effect; Ibrutinib
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2019.02.001

•Cardiovascular risks especially AF have been found to be increased in cases treated by ibrutinib Indications and dosages of anti-thrombotic drugs are important. The choice of anticoagulants in cases ibrutinib related AF is not clear enough. Although concomitant use of either AC or AP treatment with ibrutinib does not increase the risk of major bleeding the need for AC/AP therapy must be reconsidered in every case and switch must be done to low molecular weight heparin or direct oral anticoagulants if patient is receiving vitamin K antagonists. Concurrent use of warfarin is not recommended in cases with major hemorrhage.•Pharmacologic interactions between ibrutinib and P-glycoprotein substrates (digoxin and dabigatran), CYP3A4-inhibitors and inducers including anti-arrythmic drugs (verapamil and amiodarone) and direct oral anticoagulants (apixaban, rivaroxaban), antimicrobials (azoles, macrolides, rifampicin or carbamazepine) and antiepileptic drugs (carbamazepine) must be carefully considered. Patients must be informed for possible drug interactions and also monitored strictly due to the possibility of increased toxicity or decreased efficacy.•Co-incidental use of nonsteroidal anti-inflammatory drugs and herbal supplements must be questioned and special attention must be paid in the use of CYP3A4 inhibitors or inducers.•Ibrutinib must be stopped 3–7 days before invasive procedures and ibrutinib should be avoided in patients requiring dual or triple anti-coagulant and anti-platelet therapy. Bruton tyrosine kinase signaling (BTK) is critical step for B-cell development and immunoglobulin synthesis. Ibrutinib is an orally bioavailable bruton tyrosine kinase inhibitor (BTKi) and forms an irreversible covalent bound to BTK at the Cysteine-481 residue. Ibrutinib has been approved by FDA for the treatment of mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom's macroglobulinemia, marginal zone lymphoma and chronic graft-versus-host disease in allogeneic stem cell transplantation. Ibrutinib is generally well tolerated drug with rapid and durable responses but has some side events. The most common side effects are diarrhea, upper respiratory tract infection, bleeding, fatigue and cardiac side effects. These events are generally mild (grade I–II). However atrial fibrillation (AF) and bleeding are important and may be grade III or higher side effects require strict monitoring. Here side effects of ibrutinib have been summarized and important considerations in the management of these adverse events have been reviewed.