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Announcing a new treatment option for your WM patients
On behalf of Pharmacyclics LLC, an AbbVie Company, we are pleased to announce the new FDA approval for the expanded use of IMBRUVICA® (ibrutinib), in combination with rituximab for both treatment-naïve and previously treated adult patients with Waldenström’s Macroglobulinemia (WM).
For your reference, click here to read our company press release and click here to access the complete, updated Prescribing Information.
IMPORTANT SAFETY INFORMATION
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 3% of patients, with fatalities occurring in 0.3% of
1,011 patients exposed to IMBRUVICA® in clinical trials. Bleeding events of any grade, including bruising and
petechiae, occurred in 44% 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.
Infections: Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA®
therapy. Grade 3 or greater infections occurred in 24% of 1,011 patients exposed to IMBRUVICA® in clinical trials.
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 (23%), thrombocytopenia (8%),
and anemia (3%) 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 0.2% of patients, and Grade 3 or greater atrial fibrillation
and atrial flutter occurred in 4% of 1,011 patients exposed to IMBRUVICA® in clinical trials. 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.
Hypertension: Hypertension has occurred in 12% of 1,011 patients treated with IMBRUVICA® in clinical
trials with a median time to onset of 5 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 (9%) including non-skin carcinomas (2%) have occurred
in 1,011 patients treated with IMBRUVICA® in clinical trials. The most frequent second primary malignancy was
non-melanoma skin cancer (6%).
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. 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. Advise men to avoid fathering a child
during the same time period.
Adverse Reactions
The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL)
were thrombocytopenia (58%)*, neutropenia (58%)*, diarrhea (42%), anemia (39%)*, rash (31%),
musculoskeletal pain (31%), bruising (31%), nausea (28%), fatigue (27%), hemorrhage (23%), and pyrexia (20%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM
and MZL) were neutropenia (36%)*, thrombocytopenia (15%)*, and pneumonia (10%).
Approximately 7% of patients discontinued IMBRUVICA® due to adverse reactions. Adverse reactions leading to
discontinuation included hemorrhage (1.2%), atrial fibrillation (1.0%), pneumonia (1.0%), rash (0.7%),
diarrhea (0.6%), neutropenia (0.6%), sepsis (0.5%), interstitial lung disease (0.3%), bruising (0.2%),
non-melanoma skin cancer (0.2%), and thrombocytopenia (0.2%). Eight percent of patients had a dose
reduction due to adverse reactions.
*Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse reactions.
DRUG INTERACTIONS
CYP3A Inhibitors: Dose adjustments may be recommended.
CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA® in patients with severe baseline
hepatic impairment. In patients with mild or moderate impairment, reduce IMBRUVICA® dose.
Please click here for full Prescribing Information.
To learn more, please visit www.IMBRUVICAHCP.com.
Again, thank you for your shared passion in helping to advance patient care.
