ASH Clinical News ACN_4.4_SUPP_Digital Version | Page 34

Brief Summary of Prescribing Information for IMBRUVICA ® (ibrutinib)
IMBRUVICA ® (ibrutinib) capsules, for oral use
See package insert for Full Prescribing Information
INDICATIONS AND USAGE
Mantle Cell Lymphoma: IMBRUVICA is indicated for the treatment of adult
patients with mantle cell lymphoma (MCL) who have received at least one
prior therapy.
Accelerated approval was granted for this indication based on overall
response rate. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in a confirmatory trial
[see Clinical Studies (14.1) in Full Prescribing Information].
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: IMBRUVICA
is indicated for the treatment of adult patients with chronic lymphocytic
leukemia (CLL)/small lymphocytic lymphoma (SLL) [see Clinical Studies (14.2)
in Full Prescribing Information].
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with 17p deletion:
IMBRUVICA is indicated for the treatment of adult patients with chronic
lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with 17p
deletion [see Clinical Studies (14.2) in Full Prescribing Information].
Waldenström’s Macroglobulinemia: IMBRUVICA is indicated for the
treatment of adult patients with Waldenström’s macroglobulinemia (WM)
[see Clinical Studies (14.3) in Full Prescribing Information].
Marginal Zone Lymphoma: IMBRUVICA is indicated for the treatment of adult
patients with marginal zone lymphoma (MZL) who require systemic therapy
and have received at least one prior anti-CD20-based therapy.
Accelerated approval was granted for this indication based on overall response
rate [see Clinical Studies (14.4) in Full Prescribing Information]. Continued
approval for this indication may be contingent upon verification and description
of clinical benefit in a confirmatory trial.
Chronic Graft versus Host Disease: IMBRUVICA is indicated for the treatment
of adult patients with chronic graft-versus-host disease (cGVHD) after failure
of one or more lines of systemic therapy [see Clinical Studies (14.5) in Full
Prescribing Information].
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in patients treated with
IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage
[including subdural hematoma], gastrointestinal bleeding, hematuria,
and post procedural hemorrhage) have occurred in up to 6% of patients.
Bleeding events of any grade, including bruising and petechiae, occurred in
approximately half of patients treated with IMBRUVICA.
The mechanism for the bleeding events is not well understood.
IMBRUVICA may increase the risk of hemorrhage in patients receiving
antiplatelet or anticoagulant therapies and patients should be monitored
for signs of bleeding.
Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre
and post-surgery depending upon the type of surgery and the risk of bleeding
[see Clinical Studies (14) in Full Prescribing Information].
Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal)
have occurred with IMBRUVICA therapy. Grade 3 or greater infections
occurred in 14% to 29% of patients [see Adverse Reactions]. Cases of
progressive multifocal leukoencephalopathy (PML) and Pneumocystis
jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA.
Consider prophylaxis according to standard of care in patients who are at
increased risk for opportunistic infections. Monitor and evaluate patients for
fever and infections and treat appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4 cytopenias including neutropenia
(range, 13 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0
to 13%) based on laboratory measurements occurred in patients with B-cell
malignancies treated with single agent IMBRUVICA.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred
with IMBRUVICA therapy. Grade 3 or greater ventricular tachyarrhythmias
occurred in 0 to 1% of patients, and Grade 3 or greater atrial fibrillation and
atrial flutter occurred in 0 to 6% of patients. These events have occurred
particularly in patients with cardiac risk factors, hypertension, acute
infections, and a previous history of cardiac arrhythmias.
Periodically monitor patients clinically for cardiac arrhythmias. Obtain an
ECG for patients who develop arrhythmic symptoms (e.g., palpitations,
lightheadedness, syncope, chest pain) or new onset dyspnea. Manage
cardiac arrhythmias appropriately, and if it persists, consider the risks and
benefits of IMBRUVICA treatment and follow dose modification guidelines
[see Dosage and Administration (2.3) in Full Prescribing Information].
Hypertension: Hypertension (range, 6 to 17%) has occurred in patients treated
with IMBRUVICA with a median time to onset of 4.6 months (range, 0.03 to
22 months). Monitor patients for new onset hypertension or hypertension
that is not adequately controlled after starting IMBRUVICA. Adjust existing
anti-hypertensive medications and/or initiate anti-hypertensive treatment
as appropriate.
Second Primary Malignancies: Other malignancies (range, 3 to 16%) including
non-skin carcinomas (range, 1 to 4%) have occurred in patients treated
IMBRUVICA ® (ibrutinib) capsules
with IMBRUVICA. The most frequent second primary malignancy was non-
melanoma skin cancer (range, 2 to 13%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported
with IMBRUVICA therapy. Assess the baseline risk (e.g., high tumor burden)
and take appropriate precautions. Monitor patients closely and treat as
appropriate.
Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause
fetal harm when administered to a pregnant woman. Administration of ibrutinib
to pregnant rats and rabbits during the period of organogenesis caused
embryo-fetal toxicity including malformations at exposures that were 2-20
times higher than those reported in patients with hematologic malignancies.
Advise women to avoid becoming pregnant while taking IMBRUVICA and for
1 month after cessation of therapy. If this drug is used during pregnancy or
if the patient becomes pregnant while taking this drug, the patient should be
apprised of the potential hazard to a fetus [see Use in Specific Po