Ibrutinib indication

Ibrutinib indication DEFAULT

Imbruvica

Chronic lymphocytic leukaemia

In one study in 391 patients whose disease did not respond to or had come back after previous treatment, 66% of patients receiving Imbruvica were still alive after one year with their disease not having progressed compared with around 6% of patients receiving another cancer medicine, ofatumumab.

In a study involving 269 patients who had not been treated before, around 90% of patients receiving Imbruvica were still alive with their disease not having progressed after 1.5 years of treatment compared with around 52% of patients receiving a cancer medicine called chlorambucil.

In a study in 578 patients whose disease had not responded to or had come back after previous treatment, death or signs that the cancer was progressing occurred in 19% of patients who took Imbruvica together with the cancer medicines bendamustine and rituximab compared with 63% in those who took bendamustine and rituximab without Imbruvica.

In a study in 229 previously untreated patients, after 31 months, 79% of patients treated with Imbruvica and obinutuzumab were alive with their disease not having progressed compared with 36% of patients who took chlorambucil and obinutuzumab.

In another study of 529 previously untreated patients, after 3 years around 12% treated with Imbruvica and rituximab had a worsening of their disease or died compared with 25% of patients treated with chemotherapy plus rituximab.

Mantle cell lymphoma

In a study in 111 patients with mantle cell lymphoma that did not respond to or had come back after previous treatment, 21% of patients taking Imbruvica had complete response (i.e. disappearance of all signs of cancer) and 47% had partial response (i.e. the patient improved but some signs of the disease remained). The average duration of response to treatment was 17.5 months.

A second study in 280 such patients compared Imbruvica with another cancer medicine, temsirolimus. The average time before patients died or the disease got worse was 15 months with Imbruvica versus 6 months with temsirolimus.

Waldenström’s macroglobulinaemia

In one main study involving 63 patients who had previously received another treatment for Waldenström’s macroglobulinaemia, the disease responded to treatment with Imbruvica in 87% of patients. Response to treatment was measured as a reduction in the blood levels of the protein IgM, which is present in high levels in patients with Waldenström’s disease.

In a study involving 150 patients with Waldenström’s macroglobulinaemia, after 26 months, death or signs that the cancer was progressing occurred in 19% of patients who took Imbruvica together with rituximab compared with 56% of patients who took only rituximab.

Sours: https://www.ema.europa.eu/en/medicines/human/EPAR/imbruvica

IMPORTANT SIDE EFFECT INFORMATION

Before taking IMBRUVICA®, tell your healthcare provider about all of your medical 
conditions, including if you:

  • have had recent surgery or plan to have surgery. Your healthcare provider may stop IMBRUVICA® for any planned medical, surgical, or dental procedure.
  • have bleeding problems
  • have or had heart rhythm problems, smoke, or have a medical condition that increases your risk of heart disease, such as high blood pressure, high cholesterol, or diabetes
  • have an infection
  • have liver problems
  • are pregnant or plan to become pregnant. IMBRUVICA® can harm your unborn baby. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA®. Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with IMBRUVICA®. 
    • Females who are able to become pregnant should use effective birth control (contraception) during treatment with IMBRUVICA® and for 1 month after the last dose.
    • Males with female partners who are able to become pregnant should use effective birth control, such as condoms, during treatment with IMBRUVICA® and for 1 month after the last dose.
  • are breastfeeding or plan to breastfeed.  Do not breastfeed during treatment with IMBRUVICA® and for 1 week after the last dose. 

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking IMBRUVICA® with certain other medicines may affect how IMBRUVICA® works and can cause side effects.

How should I take IMBRUVICA®?

  • Take IMBRUVICA® exactly as your healthcare provider tells you to take it.
  • Take IMBRUVICA® 1 time a day.
  • Swallow IMBRUVICA® capsules or tablets whole with a glass of water.
  • Do not open, break or chew IMBRUVICA® capsules.
  • Do not cut, crush or chew IMBRUVICA® tablets.
  • Take IMBRUVICA® at about the same time each day.
  • If you miss a dose of IMBRUVICA® take it as soon as you remember on the same day. Take your next dose of IMBRUVICA® at your regular time on the next day. Do not take extra doses of IMBRUVICA® to make up for a missed dose.
  • If you take too much IMBRUVICA® call your healthcare provider or go to the nearest hospital emergency room right away. 

What should I avoid while taking IMBRUVICA®?

  • You should not drink grapefruit juice, eat grapefruit, or eat Seville oranges (often used in marmalades) during treatment with IMBRUVICA®. These products may increase the amount of IMBRUVICA® in your blood.

What are the possible side effects of IMBRUVICA®?

IMBRUVICA® may cause serious side effects, including:

  • Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA®, and can also be serious and may lead to death. Your risk of bleeding may increase if you are also taking a blood thinner medicine. Tell your healthcare provider if you have any signs of bleeding, including: blood in your stools or black stools (looks like tar), pink or brown urine, unexpected bleeding, or bleeding that is severe or that you cannot control, vomit blood or vomit looks like coffee grounds, cough up blood or blood clots, increased bruising, dizziness, weakness, confusion, change in your speech, or a headache that lasts a long time or severe headache.  
  • Infections can happen during treatment with IMBRUVICA®. These infections can be serious and may lead to death. Tell your healthcare provider right away if you have fever, chills, weakness, confusion, or other signs or symptoms of an infection during treatment with IMBRUVICA®.
  • Decrease in blood cell counts. Decreased blood counts (white blood cells, platelets, and red blood cells) are common with IMBRUVICA®, but can also be severe.  Your healthcare provider should do monthly blood tests to check your blood counts.
  • Heart problems. Serious heart rhythm problems (ventricular arrhythmias, atrial fibrillation, and atrial flutter), heart failure, and death have happened in people treated with IMBRUVICA®, especially in people who have an increased risk for heart disease, have an infection, or who have had heart rhythm problems in the past. Tell your healthcare provider if you get any symptoms of heart problems, such as feeling as if your heart is beating fast and irregular, lightheadedness, dizziness, shortness of breath, swelling of the feet, ankles, or legs, chest discomfort, or you faint.  If you develop any of these symptoms, your healthcare provider may do a test to check your heart (ECG) and may change your IMBRUVICA® dose.
  • High blood pressure (hypertension). New or worsening high blood pressure has happened in people treated with IMBRUVICA®. Your healthcare provider may start you on blood pressure medicine or change current medicines to treat your blood pressure.
  • Second primary cancers. New cancers have happened during treatment with IMBRUVICA®, including cancers of the skin or other organs.
  • Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure and the need for dialysis treatment, abnormal heart rhythm, seizure, and sometimes death. Your healthcare provider may do blood tests to check you for TLS.

The most common side effects of IMBRUVICA® in adults with B-cell malignancies (MCL, CLL/SLL, WM and MZL) include:

  • diarrhea
  • tiredness
  • muscle and bone pain

The most common side effects of IMBRUVICA® in adults with cGVHD include:

  • tiredness
  • bruising
  • diarrhea
  • mouth sores (stomatitis)
  • muscle spasms
  • nausea

Diarrhea is a common side effect in people who take IMBRUVICA®. Drink plenty of fluids during treatment with IMBRUVICA® to help reduce your risk of losing too much fluid (dehydration) due to diarrhea. Tell your healthcare provider if you have diarrhea that does not go away.

These are not all the possible side effects of IMBRUVICA®. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of IMBRUVICA®

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IMBRUVICA® for a condition for which it was not prescribed. Do not give IMBRUVICA® to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about IMBRUVICA® that is written for health professionals.

Please see the full Important Product Information.

Sours: https://imbruvica.com/
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Leading the way with a wave of evidence

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA® in 27 clinical trials. Bleeding events of any grade including bruising and petechiae occurred in 39%, and excluding bruising and petechiae occurred in 23% of patients who received IMBRUVICA®, respectively.

The mechanism for the bleeding events is not well understood.

Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage. The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms 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 21% of 1,476 patients who received 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: In 645 patients with B-cell malignancies who received IMBRUVICA® as a single agent, grade 3 or 4 neutropenia occurred in 23% of patients, grade 3 or 4 thrombocytopenia in 8% and grade 3 or 4 anemia in 3%, based on laboratory measurements.

Monitor complete blood counts monthly.

Cardiac Arrhythmias and Cardiac Failure: Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA®. Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of patients, Grade 3 or greater atrial fibrillation and atrial flutter occurred in 4%, and Grade 3 or greater cardiac failure occurred in 1% of 1,476 patients who received 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.

At baseline and then periodically, monitor patients clinically for cardiac arrhythmias and cardiac failure. Obtain an ECG for patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness, syncope, chest pain) or new onset dyspnea. Manage cardiac arrhythmias and cardiac failure appropriately, and if it persists, consider the risks and benefits of IMBRUVICA® treatment and follow dose modification guidelines.

Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA® in clinical trials. Grade 3 or greater hypertension occurred in 8% of patients. Based on data from 1,124 of these patients, the median time to onset was 5.9 months (range, 0.03 to 24 months).

Monitor blood pressure in patients treated with IMBRUVICA® and initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA® as appropriate.

Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (4%), occurred among the 1,476 patients who received 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®. 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 pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥30%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%), musculoskeletal pain (38.8%), neutropenia (38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%).

The most common Grade ≥ 3 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%), and hypertension (8.0%).

Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] 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%)*, muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were pneumonia (14%), fatigue (12%), diarrhea (10%), neutropenia (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.

DRUG INTERACTIONS

CYP3A Inhibitors: Co-administration of IMBRUVICA® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. Dose modifications of IMBRUVICA® may be recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors. Interrupt IMBRUVICA® if strong inhibitors are used short-term (e.g., for ≤ 7 days). See dose modification guidelines in USPI sections 2.3 and 7.1.

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 hepatic impairment. In patients with mild or moderate impairment, reduce recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA®.

Please see full Prescribing Information.

Sours: https://www.imbruvicahcp.com/
Adverse Events of Ibrutinib in Chronic Lymphocytic Leukemia

IMBRUVICA® (ibrutinib) Receives 11th FDA Approval

NORTH CHICAGO, Ill., April 21, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) approved the use of IMBRUVICA® (ibrutinib) in combination with rituximab for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This milestone marks the 11th FDA approval for IMBRUVICA since it was first approved in 2013 and the sixth in CLL, the most common form of leukemia in adults.1  

"The gold-standard first-line treatment option for many patients with chronic lymphocytic leukemia who were fit enough to tolerate an aggressive treatment course had been the intravenous chemoimmunotherapy of FCR – that is, until today," said Brian Koffman, M.D., C.M., Chief Medical Officer and Executive Vice President, CLL Society. "The FDA approval of ibrutinib and rituximab regimen is welcome news for these previously untreated patients who have been looking forward to a non-chemotherapy treatment option. The results from ECOG-ACRIN's E1912 clinical trial in previously untreated, younger adult patients and today's milestone represent a paradigm shift in how physicians can treat patients with CLL and may enable many to choose a non-chemotherapy treatment option."

The approval is based on positive results from the landmark Phase 3 E1912 study, which was designed and conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). This is the third Phase 3 randomized study in the treatment of previously untreated CLL patients incorporated into the medicine's U.S. prescribing information. In addition to the Real-Time Oncology Review (RTOR) pilot program and priority review, the approval was granted under the FDA's recently established Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for submission and review of oncology medicine applications among multiple regulatory agencies worldwide.

"With eleven FDA approvals in six years, this latest CLL label update for IMBRUVICA further underscores the impact of this important medicine in the first-line setting," said Danelle James, M.D., M.A.S., IMBRUVICA Clinical Development Lead, Pharmacyclics LLC, an AbbVie company. "IMBRUVICA enables long-term disease management and now has demonstrated superior progression-free survival compared to a standard chemoimmunotherapy regimen. Today, many patients who were previously considered appropriate for chemotherapy now have an alternative treatment option."

The E1912 study demonstrated previously untreated patients (aged 70 or younger) with CLL lived longer without disease progression – as measured by statistically significant progression-free survival (PFS) – with IMBRUVICA plus rituximab compared to those treated with the potent chemoimmunotherapy regimen comparator of fludarabine, cyclophosphamide and rituximab (FCR). At a median follow-up of 37 months, IMBRUVICA plus rituximab significantly improved PFS compared to FCR (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.22-0.52; p<0.0001). With a median follow-up time of 49 months, median overall survival was not reached with a total of 23 deaths: 11 (3%) in the IMBRUVICA plus rituximab and 12 (7%) in the FCR treatment arms. Extended follow-up results from the E1912 study were most recently presented in an oral session at the 2019 American Society of Hematology (ASH) Annual Meeting.

In the E1912 study, the most common adverse reactions (occurring in 30% or more of patients) of all Grades in patients treated with IMBRUVICA plus rituximab compared to patients treated with FCR were fatigue (80% vs. 78%), musculoskeletal pain* (61% vs. 35%), diarrhea (53% vs. 27%), rash* (49% vs. 29%), hypertension* (42% vs. 22%), arthralgia (41% vs. 10%), nausea (40% vs. 64%), headache (40% vs. 27%), bruising* (36% vs. 4%), cough (32% vs. 25%) and hemorrhage* (31% vs. 8%).

The recommended dosage of IMBRUVICA for CLL/SLL is 420 mg orally once a day until disease progression or unacceptable toxicity. For adults with CLL/SLL, IMBRUVICA can be administered as a single agent, in combination rituximab or obinutuzumab, or in combination with bendamustine and rituximab (BR). When administering IMBRUVICA in combination with rituximab or obinutuzumab, consider administering IMBRUVICA prior to rituximab or obinutuzumab when given on the same day.

*Includes multiple adverse drug reaction terms.

About the E1912 Study2 
The Phase 3 E1912 study evaluated 529 previously untreated CLL patients ages 70 or younger (median age of 58) who were randomly assigned in a 2:1 fashion to receive IMBRUVICA plus rituximab (N=354) or the chemoimmunotherapy FCR (N=175). The primary endpoint was PFS.

The study was led by ECOG-ACRIN with study site participation by groups in the NCI's National Clinical Trials Network (Alliance for Clinical Trials in Oncology, ECOG-ACRIN, NRG Oncology and SWOG), and was sponsored by the NCI. Pharmacyclics LLC supported the study through a Cooperative Research and Development Agreement with the NCI.

About IMBRUVICA
IMBRUVICA is a once-daily, first-in-class Bruton's tyrosine kinase (BTK) inhibitor that is administered orally, and is jointly developed and commercialized by Pharmacyclics, LLC, an AbbVie Company and Janssen Biotech, Inc. The BTK protein sends important signals that tell B cells to mature and produce antibodies. BTK signaling is needed by specific cancer cells to multiply and spread.3,4 By blocking BTK, IMBRUVICA may help move abnormal B cells out of their nourishing environments in the lymph nodes, bone marrow, and other organs.5

Since its launch in 2013, IMBRUVICA has received 11 FDA approvals across six disease areas: chronic lymphocytic leukemia (CLL) with or without 17p deletion (del17p); small lymphocytic lymphoma (SLL) with or without del17p; Waldenström's macroglobulinemia (WM); previously-treated patients with mantle cell lymphoma (MCL)*; previously-treated patients with marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy* – and previously-treated patients with chronic graft-versus-host disease (cGVHD) after failure of one or more lines of systemic therapy.6

IMBRUVICA is now approved in 95 countries and has been used to treat more than 195,000 patients worldwide across its approved indications. IMBRUVICA is the only FDA-approved medicine in WM and cGVHD. IMBRUVICA has been granted four Breakthrough Therapy Designations from the U.S. FDA. This designation is intended to expedite the development and review of a potential new drug for serious or life-threatening diseases. IMBRUVICA was one of the first medicines to receive FDA approval via the Breakthrough Therapy Designation pathway.

In early 2019, the National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 28 leading cancer centers devoted to patient care, research, and education, recommends ibrutinib (IMBRUVICA) as a preferred regimen for the initial treatment of CLL/SLL and it is the only Category 1 treatment for treatment-naïve patients without deletion 17p. In February 2020, the NCCN Guidelines® were updated to elevate IMBRUVICA with or without rituximab from other recommended regimens to a preferred regimen for the treatment of relapsed/refractory MCL.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. IMBRUVICA is the most comprehensively studied BTK inhibitor, with more than 150 ongoing clinical trials. There are approximately 30 ongoing company-sponsored trials, 14 of which are in Phase 3, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. For more information, visit www.IMBRUVICA.com.

*Accelerated approval was granted for the MCL and MZL indications based on overall response rate. Continued approval for MCL and MZL may be contingent upon verification and description of clinical benefit in confirmatory trials.

 

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Fatal bleeding events have occurred in patients who received IMBRUVICA®. Major hemorrhage (≥ Grade 3, serious, or any central nervous system events; e.g., intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post procedural hemorrhage) occurred in 4% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA® in 27 clinical trials. Bleeding events, including bruising and petechiae, occurred in 39% of patients who received IMBRUVICA®.

The mechanism for the bleeding events is not well understood.

Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA® increases the risk of major hemorrhage. Across clinical trials, 3.1% of 2,838 patients who received IMBRUVICA® without antiplatelet or anticoagulant therapy experienced major hemorrhage.  The addition of antiplatelet therapy with or without anticoagulant therapy increased this percentage to 4.4%, and the addition of anticoagulant therapy with or without antiplatelet therapy increased this percentage to 6.1%.  Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA®. Monitor for signs and symptoms 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 21% of 1,476 patients who received 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: In 645 patients with B?cell malignancies who received IMBRUVICA® as a single agent, Grade 3 or 4 neutropenia occurred in 23% of patients, Grade 3 or 4 thrombocytopenia in 8% and Grade 3 or 4 anemia in 3%, based on laboratory measurements.

Monitor complete blood counts monthly.

Cardiac Arrhythmias: Fatal and serious cardiac arrhythmias have occurred with IMBRUVICA®. 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 1,476 patients who received 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 occurred in 19% of 1,476 patients who received IMBRUVICA® in clinical trials.  Grade 3 or greater hypertension occurred in 8% of patients. Based on data from 1,124 of these patients, the median time to onset was 5.9 months (range, 0.03 to 24 months).   

Monitor blood pressure in patients treated with IMBRUVICA® and initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA® as appropriate.

Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (4%), occurred among the 1,476 patients who received 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®. 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 pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMBRUVICA® and for 1 month after the last dose. Advise males with female partners of reproductive potential to use effective contraception during the same time period.

ADVERSE REACTIONS

B-cell malignancies: The most common adverse reactions (≥30%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were thrombocytopenia (54.5%)*, diarrhea (43.8%), fatigue (39.1%), musculoskeletal pain (38.8%), neutropenia (38.6%)*, rash (35.8%), anemia (35.0%)*, and bruising (32.0%).

The most common Grade ≥ 3 adverse reactions (≥5%) in patients with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (20.7%)*, thrombocytopenia (13.6%)*, pneumonia (8.2%), and hypertension (8.0%).

Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of patients had a dose reduction due to adverse reactions. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] 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%)*, muscle spasms (29%), stomatitis (29%), nausea (26%), hemorrhage (26%), anemia (24%)*, and pneumonia (21%).

The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were pneumonia (14%), fatigue (12%), diarrhea (10%), neutropenia (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.

DRUG INTERACTIONS

CYP3A Inhibitors: Co-administration of IMBRUVICA® with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations.  Dose modifications of IMBRUVICA® may be recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. Avoid concomitant use of other strong CYP3A inhibitors.  Interrupt IMBRUVICA® if strong inhibitors are used short-term (e.g., for ≤ 7 days).  See dose modification guidelines in USPI sections 2.4 and 7.1.

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 recommended IMBRUVICA® dose and monitor more frequently for adverse reactions of IMBRUVICA®.

 

Please click here for full Prescribing Information.

 

About AbbVie
AbbVie is a global, research and development-based biopharmaceutical company committed to developing innovative advanced therapies for some of the world's most complex and critical conditions. The company's mission is to use its expertise, dedicated people and unique approach to innovation to markedly improve treatments across four primary therapeutic areas: immunology, oncology, virology and neuroscience. In more than 75 countries, AbbVie employees are working every day to advance health solutions for people around the world. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

IMBRUVICA is a registered trademark of Pharmacyclics LLC.

CCRC-04364 4/20

1 American Society of Hematology. Leukemia. http://www.hematology.org/Patients/Cancers/Leukemia.aspx. Accessed February 2020.
2 Shanafelt, T., et al. Ibrutinib–Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. The New England Journal of Medicine. August 1, 2019. https://www.nejm.org/doi/full/10.1056/NEJMoa1817073. Accessed January 2020.
3 Genetics Home Reference. Isolated growth hormone deficiency. http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency. Accessed January 2020.
4 Turetsky, et al. Single cell imaging of Bruton's Tyrosine Kinase using an irreversible inhibitor. Scientific Reports. volume 4, Article number: 4782 (2014).
5 de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
6 IMBRUVICA U.S. Prescribing Information, April 2020.

 

SOURCE AbbVie

Sours: https://news.abbvie.com/news/press-releases/imbruvica-ibrutinib-receives-11th-fda-approval.htm

Indication ibrutinib

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Adverse Events of Ibrutinib in Chronic Lymphocytic Leukemia

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