05.11.18 Press Release

Important Update for Healthcare Professionals and Patients Regarding IMBRUVICA® (ibrutinib)

Posted: 7:00 a.m. PST, May 11, 2018 

IMPORTANT UPDATE FOR HEALTHCARE PROFESSIONALS AND PATIENTS REGARDING IMBRUVICA® (IBRUTINIB)

For the past five years, we have been proud to offer IMBRUVICA® (ibrutinib) to patients facing serious blood cancers, such as leukemia and lymphoma. We are privileged and honored to be part of the blood cancer community and we look forward to building on that legacy. 

Earlier this year, we introduced a new single-tablet formulation of IMBRUVICA as an innovation for patients with a convenient one pill, once-a-day dosing regimen. This new formulation was developed with the intention of improving daily adherence. Since the introduction of this new tablet formulation in late March, it has been adopted by the majority of patients on IMBRUVICA.

However, we have received feedback regarding the availability of IMBRUVICA capsules, and as a result will continue to offer 140 mg IMBRUVICA capsules as an option in addition to our one pill, once-a-day tablet.

Consistent with our commitment to optimal customer experience, we are also looking at ways to improve our service offerings, including our YOU&i support program. 

We are committed to exploring ways of providing IMBRUVICA in a form that works best for patients and healthcare professionals by continuing to listen to their insights and medication preferences by maintaining an ongoing dialogue.
 
Additional information on our single-tablet formulation of IMBRUVICA here.

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Additional Information about IMBRUVICA® 

INDICATIONS

IMBRUVICA® is indicated to treat adults withi 

• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) 

• Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion

• Waldenström’s macroglobulinemia (WM) 

• Mantle cell lymphoma (MCL) patients who have received at least one prior therapy
     o 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.

• Marginal zone lymphoma (MZL) patients who require systemic therapy and have received at least one prior anti-CD20-based therapy
     o 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.

• Chronic Graft-Versus-Host Disease (cGVHD) patients who failed one or more lines of systemic therapy

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 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. 

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. 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. 

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 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. 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 

B-cell malignancies: The most common adverse reactions (≥20%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (62%)*, neutropenia (61%)*, diarrhea (43%), anemia (41%)*, musculoskeletal pain (30%), bruising (30%), rash (30%), fatigue (29%), nausea (29%), hemorrhage (22%), and pyrexia (21%). 

The most common Grade 3 or 4 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%)*, thrombocytopenia (16%)*, and pneumonia (10%). 

Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4%-10% (CLL/SLL), 9% (MCL), and 9 % (WM [6%] and MZL [13%]) of patients discontinued due to adverse reactions. 

cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, stomatitis (29%), muscle spasms (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%). 

The most common Grade 3 or 4 adverse reactions (≥5%) reported in patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia (10%)*, pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%), musculoskeletal pain (5%), and pyrexia (5%). 

Twenty-four percent of patients receiving IMBRUVICA® in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions leading to dose reduction occurred in 26% of patients. 
*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 see Full Prescribing Information: https://www.imbruvica.com/prescribing-information.

i Janssen Biotech, Inc., Pharmacyclics LLC. IMBRUVICA U.S. Prescribing Information. February 2018.