This indication is approved under accelerated approval based on overall response rate. IMBRUVICA is a kinase inhibitor indicated for the treatment of: Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy (1.1). For any questions about the Pharmacyclics Privacy Policy, please visit www.pharmacyclics.com. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Mechanism of action Elevated intraocular pressure is a characteristic manifestation of ocular hypertension or open-angle glaucoma. Approximately 4-10% (CLL/SLL), 9% (MCL), and 7% (WM [5%] and MZL [13%]) of patients discontinued due to adverse reactions. Take IMBRUVICA exactly as your healthcare provider tells you to take it. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. 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 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. As with any pharmaceutical drug, use of Imbruvica can lead to a range of side effects. CYP3A Inducers: Avoid coadministration with strong CYP3A inducers. Advise males with female partners of reproductive potential to use effective contraception during the same time period. Grade 3 or greater hypertension occurred in 8% of patients. 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%. IMBRUVICA is a kinase inhibitor indicated for the treatment of: Your use of the information on this site is subject to the terms of theLegal Noticeand newPrivacy Policyof Pharmacyclics LLC. The most frequent second primary malignancy was non-melanoma skin cancer (6%). Imbruvica received marketing approval from European Union (EU) in October 2014. You are leaving the patient and caregiver site and entering the US Healthcare professional site. The FDA granted approval for Imbruvica for the treatment of MCL patients in November 2013. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). The mechanism for the bleeding events is not well understood. Abstract 923. Adult patients with Waldenstrm's macroglobulinemia (WM). Approximately 9% (CLL/SLL), 14% (MCL), 14% (WM) and 10% (MZL) of adult patients had a dose reduction due to adverse reactions. TAp63 regulates VLA-4 expression and chronic lymphocytic leukemia cell migration to the bone marrow in a CD74-dependent manner. Pharmacyclics LLC recognizes that the Internet is a global communication medium; however laws, regulatory requirements, and medical practices vary from country to country. Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. By clicking "OK" below you will be taken to a website that may contain links or references to other websites to which our Privacy Policy may not apply. Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression. Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. Tumor Lysis Syndrome: Tumor lysis syndrome has been infrequently reported with IMBRUVICA. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA in clinical trials. As demonstrated byin vitroandin vivostudies. Imbruvica was developed under the FDAs accelerated approval programme. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Assess the baseline risk (e.g., high tumor burden) and take appropriate precautions. Presented at: 104th Annual Meeting of the American Association for Cancer Research; April 6-10, 2013; Washington, DC. Modulates chemotaxis and trafficking 1,5,7,9,11-14 * As demonstrated by in vitro and in vivo studies. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA treatment. The most common Grade 3 adverse reactions (5%) in adult 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%). Burger JA, Ghia P, Rosenwald A, Caligaris-Cappio F. The microenvironment in mature B-cell malignancies: a target for new treatment strategies. 1,3 Treatment-related lymphocytosis occurred in 66% of patients treated with single-agent IMBRUVICA across the CLL/SLL registration studies 4 Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. Advise pregnant women of the potential risk to a fetus. For any questions about the Pharmacyclics Privacy Policy, please visit www.pharmacyclics.com. Pediatric Use: The safety and effectiveness of IMBRUVICA have not been established for the treatment of cGVHD after failure of one or more lines of therapy in pediatric patients less than 1 year of age. Janssen conducted the Phase II clinical trials between February 2011 and June 2013. Monitor for signs and symptoms of bleeding.. We encourage you to read the Privacy Policy of every website you visit. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). Monitor patients closely and treat as appropriate. cGVHD: The most common adverse reactions (20%) in adult or pediatric patients with cGVHD were fatigue (57%), anemia (49%)*, bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, musculoskeletal pain (30%), pyrexia (30%), muscle spasms (29%), stomatitis (29%), hemorrhage (26%), nausea (26%), abdominal pain (23%), pneumonia (23%), and headache (21%). Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA treatment. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. Cinar M, Hamedani F, Mo Z, et al. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have occurred in patients treated with IMBRUVICA. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Previously Treated Marginal Zone Lymphoma*, Previously Treated Chronic Graft Versus Host Disease. Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. These events have occurred particularly in patients with cardiac risk factors including hypertension and diabetes mellitus, a previous history of cardiac arrhythmias, and in patients with acute infections. Monitor blood pressure in patients treated with IMBRUVICA, initiate or adjust anti-hypertensive medication throughout treatment with IMBRUVICA as appropriate, and follow dosage modification guidelines for Grade 3 or higher hypertension. Grade 3 or greater infections occurred in 21% of 1,476 patients who received IMBRUVICA in clinical trials. Honigberg LA, Smith AM, Sirisawad M, et al. Mechanism: Related to mechanism of action; inhibits B-cell function, increasing the risk for opportunistic infections, . Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A. Monitor complete blood counts monthly. Honigberg LA, Smith AM, Sirisawad M, et al. You are leaving the patient and caregiver site and entering the US Healthcare professional site. IMBRUVICA(ibrutinib) is covered by U.S. Mantle cell lymphoma cells express high levels of CXCR4, CXCR5, and VLA-4 (CD49d): importance for interactions with the stromal microenvironment and specific targeting. Click OK below if you are a healthcare professional. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Advise females of reproductive potential to use effective contraception during IBRANCE treatment and for at least 3 weeks after the last dose. Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Patients with cGVHD: Avoid use of IMBRUVICA in patients with total bilirubin level > 3x upper limit of normal (ULN) (unless of non-hepatic origin or due to Gilberts syndrome). IMBRUVICA is a kinase inhibitor indicated for the treatment of: Your use of the information on this site is subject to the terms of theLegal Noticeand newPrivacy Policyof Pharmacyclics LLC. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients who received IMBRUVICA in clinical trials. Abstract 923. 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 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Hypertension: Hypertension occurred in 19% of 1,476 patients who received IMBRUVICA in clinical trials. The primary outcome measure of the study was to measure the number of participants with a response to the drug. If your healthcare provider prescribes IMBRUVICA capsules or tablets: Swallow IMBRUVICA capsules or tablets whole with a glass of water. Ibrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. Image courtesy of Nephron. Discontinuation of IMBRUVICA treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain strong or moderate inhibitors of CYP3A. The drug is available in the form of 140mg capsules for oral administration, and sold in 90 and 120 capsule boxes. View Imbruvica mechanism of action for pharmacodynamics and pharmacokinetics details. Patients who received ibrutinib also lived . Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Though the precise mechanism of action of the drug is not known completely, it is presumed the drug works by stopping the malignant B-cell proliferation and survival. Pharmacyclics LLC recognizes that the Internet is a global communication medium; however laws, regulatory requirements, and medical practices vary from country to country. Adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. The most common Grade 3 or higher adverse reactions (5%) reported in adult or pediatric patients with cGVHD were pneumonia (14%), anemia (13%)*, fatigue (12%), pyrexia (11%), diarrhea (10%), neutropenia (10%)*, sepsis (10%), osteonecrosis (9%), stomatitis (9%), hypokalemia (7%), headache (5%), and musculoskeletal pain (5%). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Pharmacyclics LLC recognizes that the Internet is a global communication medium; however laws, regulatory requirements, and medical practices vary from country to country. Based on data from 1,124 of these patients, the median time to onset was 5.9 months (range, 0.03 to 24 months). In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. Adult Patients with B-cell Malignancies: Hepatic Impairment (based on Child-Pugh criteria): Avoid use of IMBRUVICA in patients with severe hepatic impairment. The safety and effectiveness of IMBRUVICA in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. Inhibits proliferation and survival 1-6 2. Avoid concomitant use of other strong CYP3A inhibitors. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. IMBRUVICA Mechanism of Action Ibrutinib is a small-molecule inhibitor of BTK. Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy. Manage cardiac arrhythmias and cardiac failure appropriately, follow dose modification guidelines, and consider the risks and benefits of continued IMBRUVICA treatment. CYP3A Inhibitors:Co-administration of IMBRUVICA with strong or moderate CYP3A inhibitors may increase ibrutinib plasma concentrations. The drug was also approved by the FDA for the treatment of Waldenstroms macroglobulinemia (WM) in January 2015. . Increased ibrutinib concentrations may increase the risk of drug-related toxicity. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Mechanism of action Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Second Primary Malignancies: Other malignancies (10%), including non-skin carcinomas (3.9%), occurred among the 1,476 patients who received IMBRUVICA in clinical trials. Grade 3 or greater ventricular tachyarrhythmias were reported in 0.2%, Grade 3 or greater atrial fibrillation and atrial flutter were reported in 3.7%, and Grade 3 or greater cardiac failure was reported in 1.3% of 4,896 patients who received IMBRUVICA in clinical trials, including in patients who received IMBRUVICA in unapproved monotherapy or combination regimens. Consider the risks and benefits of anticoagulant or antiplatelet therapy when co-administered with IMBRUVICA. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Hemorrhage:Fatal bleeding events have occurred in patients who received IMBRUVICA. Chang BY, Francesco M, Steggerda S, et al. Reduce recommended dose when administering IMBRUVICA to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilberts syndrome). Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Blocking BTK inhibits the B-cell receptor pathway, which is often aberrantly active in B cell cancers. Chang BY, Francesco M, Steggerda S, et al. In patients with mild or moderate impairment, reduce recommended IMBRUVICA dose and monitor more frequently for adverse reactions of IMBRUVICA. Obtain further evaluation (e.g., ECG, echocardiogram) as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. This site is published by Pharmacyclics LLC which has developed the content in conjunction with Janssen Biotech, Inc. Any information that is collected on this site may be shared between Pharmacyclics LLC and Janssen Biotech, Inc. Embryo-Fetal Toxicity: Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. In the randomized population from a study that included 35 patients (26 pediatric patients age 5 to less than 17 years) with previously treated mature B-cell non-Hodgkin lymphoma, major hemorrhage and discontinuation of chemoimmunotherapy due to adverse reactions occurred more frequently in the ibrutinib plus chemoimmunotherapy arm compared to the chemoimmunotherapy alone arm. B-cell malignancies: The most common adverse reactions (30%) in adult 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%). Patents, which are listed in FDA's Orange Book (available athttps://www.accessdata.fda.gov/scripts/cder/ob/default.cfm). Adult patients with Waldenstrm's macroglobulinemia (WM). Avoid concomitant use of other strong CYP3A inhibitors. imbruvica Dosage is a powerful low-molecular weight inhibitor of Bruton's tyrosine kinase (TCB). The mechanism for the bleeding events is not well understood. Imbruvica (ibrutinib) mechanism of action Imbruvica contains a small-molecule inhibitor of Bruton's tyrosine kinase (BTK). The most common Grade 3 adverse reactions (5%) in adult 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%). Adverse reactions leading to dose reduction occurred in 26% of adult patients and 19% of pediatric patients. *Treatment-emergent decreases (all grades) were based on laboratory measurements. Inhibits proliferation and survival 1-6 2. Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). The mechanism for the bleeding events is not well understood. This indication is approved under accelerated approval based on overall response rate. The FDA approval for Imbruvica was based on results obtained from a Phase II clinical trial. Honigberg LA, Smith AM, Sirisawad M, et al. Burger JA, Buggy JJ. Avoid concomitant use of other strong CYP3A inhibitors. de Rooij MFM, Kuil A, Geest CR, et al. Inhibits adhesion 1,6-11 3. Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL). Monitor for signs and symptoms of bleeding.. Inhibits adhesion 1,6-11 3. This site is published by Pharmacyclics LLC which has developed the content in conjunction with Janssen Biotech, Inc. Any information that is collected on this site may be shared between Pharmacyclics LLC and Janssen Biotech, Inc. It is also found that more than 9% of patients discontinued the treatment because of adverse reactions. The enzyme in your body that Imbruvica targets is called Bruton's tyrosine kinase (BTK). Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Several studies have shown that improper activation of both of these types of immune cells are common in chronic GVHD. Inhibits proliferation and survival 1-6 2. Imbruvica was approved by the FDA in November 2013. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Hemorrhage:Fatal bleeding events have occurred in patients who received IMBRUVICA. Click OK below if you are a healthcare professional. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death:Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). We encourage you to read the Privacy Policy of every website you visit. BTK=Brutons tyrosine kinase, CLL=chronic lymphocytic leukemia, SLL=small lymphocytic lymphoma. MIMS Class Targeted Cancer Therapy ATC Classification L01EL01 - ibrutinib ; Belongs to the class of Bruton's tyrosine kinase (BTK) inhibitors. Patents, which are listed in FDA's Orange Book (available athttps://www.accessdata.fda.gov/scripts/cder/ob/default.cfm). The tumour response was evaluated according to the revised International Working Group (IWG) for non-Hodgkin Lymphoma criteria. . Dose modifications of IMBRUVICA are recommended when used concomitantly with posaconazole, voriconazole, and moderate CYP3A inhibitors. A study published in 2014 showed that treatment with ibrutinib alleviated symptoms in mouse models of corticosteroid-resistant GVHD. 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 4.2% of patients, with fatalities occurring in 0.4% of 2,838 patients who received IMBRUVICA in 27 clinical trials. Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Honigberg LA, Smith AM, Sirisawad M, et al. They include the following. This site is published by Pharmacyclics LLC which has developed the content in conjunction with Janssen Biotech, Inc. Any information that is collected on this site may be shared between Pharmacyclics LLC and Janssen Biotech, Inc. Ibrutinib inhibits malignant cell adhesion and migration and reduces tumor burden in lymph node and bone marrow in a murine model of mantle cell dissemination and progression. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. See dose modification guidelines in USPI sections 2.3 and 7.1. *Treatment-emergent decreases (all grades) were based on laboratory measurements. Monitor complete blood counts monthly. Swallow the tablet or capsule whole and do not crush, chew, break, or open it. Our services are intended for corporate subscribers and you warrant that the email address submitted is your corporate email address. The safety and effectiveness of IMBRUVICA in pediatric patients have not been established in MCL, CLL/SLL, CLL/SLL with 17p deletion, WM, MZL or in patients with mature B-cell non-Hodgkin lymphoma. Monitor patients closely and treat as appropriate. Reduce recommended dose when administering IMBRUVICA to patients with total bilirubin level > 1.5 to 3x ULN (unless of non-hepatic origin or due to Gilberts syndrome). 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 2.8%, based on laboratory measurements. IMBRUVICA (ibrutinib) inhibits BTK to disrupt 3 key B-cell processes* 1. Discontinuation of IMBRUVICA treatment due to an adverse reaction occurred in 24% of adult patients and 23% of pediatric patients. Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion. The most common Grade 3 adverse reactions (5%) in adult 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%). The most frequent second primary malignancy was non-melanoma skin cancer (6%). IMBRUVICA(ibrutinib) is covered by U.S. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. The most common Grade 3 or 4 non-haematological adverse reactions found during the clinical study included pneumonia, abdominal pain, atrial fibrillation, diarrhoea, skin infections, and fatigue. Chang BY, Francesco M, de Rooij MFM, et al. Modulates chemotaxis and trafficking 1,5,7,9,11-14 * As demonstrated by in vitro and in vivo studies. Grade 3 or greater hypertension occurred in 8% of patients. Increased ibrutinib concentrations may increase the risk of drug-related toxicity.