Concomitant treatment with supportive care therapies for cGVHD was permitted. Imbruvica (ibrutinib) oral suspension contains 70 mg/mL ibrutinib (active ingredient) and the following inactive ingredients: benzyl alcohol, citric acid monohydrate, disodium hydrogen phosphate, hypromellose, microcrystalline cellulose and carboxymethylcellulose sodium, purified water and sucralose. Imbruvica comes as capsules, tablets, and oral suspension. Limitations of use: ZYDELIG is not indicated and is not recommended for first-line treatment of any . At baseline, 89% of patients had a baseline ECOG performance status of 0 or 1. Package insert / prescribing information The median time since cGVHD diagnosis was 14 months, the median number of prior cGVHD treatments was 2 (range, 1 to 3 treatments), and 60% of patients had a Karnofsky performance score of 80. Do not breastfeed during treatment with Imbruvica and for 1 week after the last dose. The most frequent second primary malignancy was non-melanoma skin cancer (6%). Do not open, break, or chew the capsules. Permanent discontinuation of Imbruvica due to an adverse reaction occurred in 23% of patients. You can ask your pharmacist or healthcare provider for information about IMBRUVICA that is written for health professionals. Requires no dose adjustment with acid-reducing agents 2,3. The recommended dosage of Imbruvica for patients age 12 years and older with cGVHD is 420 mg orally once daily, and for patients 1 to less than 12 years of age with cGVHD is 240 mg/m, Dose (mg) of Imbruvica Capsules/Tablets to Administer, Volume (mL) of Imbruvica Oral Suspension (70 mg/mL) to Administer, Dose Modification for MCL and MZL After Recovery, Dose Modification for CLL/SLL, WM, and Patients 12 Years or older with cGVHD After Recovery, Dose Modification for Patients 1 Year to less than 12 Years with cGVHD After Recovery, Avoid the use of Imbruvica in these patients with total bilirubin level > 3 x ULN (unless of non-hepatic origin or due to Gilberts syndrome), 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. In randomized controlled trials (n=2,115; median treatment duration of 19.1 months for 1,157 patients treated with Imbruvica and 5.3 months for 958 patients in the control arm), blurred vision and decreased visual acuity of any grade occurred in 11% of patients treated with Imbruvica (9% Grade 1, 2% Grade 2, no Grade 3 or higher) compared to 6% in the control arm (5% Grade 1 and <1% Grade 2 and 3). Advise females of reproductive potential to use effective contraception during treatment with Imbruvica and for 1 month after the last dose [see Use in Specific Populations (8.3)]. Shake well before each use In pediatric patients with cGVHD treated with ibrutinib at 240 mg/m2 once daily (patients age 1 to <12 years) or 420 mg once daily (patients age 12 years), the geometric mean (%CV) steady state AUC and Cmax in patients age 1 to <12 years is 467 (102%) ngh/mL and 65.7 (96%) ng/mL, respectively, and in patients age 12 to <17 years is 966 (78%) ngh/mL and 149 (79%) ng/mL, respectively. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Use of either anticoagulant or antiplatelet agents concomitantly with IMBRUVICA increases the risk of major hemorrhage. Interrupt IMBRUVICA if strong inhibitors are used short-term (e.g., for 7 days). Air bubbles must be removed to ensure the correct dose. Make sure the bottle is tightly closed between each use. RESONATE-2 included 267 randomized patients with treatment nave CLL or SLL who were 65 years or older and received single agent Imbruvica or chlorambucil. Repeat with second syringe if needed to complete the prescribed dose. Revised: 8/2022. The most common reasons for initiating CLL therapy include: progressive marrow failure demonstrated by anemia and/or thrombocytopenia (38%), progressive or symptomatic lymphadenopathy (37%), progressive or symptomatic splenomegaly (30%), fatigue (27%) and night sweats (25%). Read this Instructions for Use before you give Imbruvica to your child, and each time you get a refill. Twenty-four percent of patients receiving Imbruvica in Study 1129 discontinued treatment due to adverse reactions. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities. Patients (n = 229) were randomized 1:1 to receive either Imbruvica 420 mg daily until disease progression or unacceptable toxicity or chlorambucil at a dose of 0.5 mg/kg on Days 1 and 15 of each 28-day cycle for 6 cycles. Four to 10 percent of patients with CLL/SLL receiving Imbruvica discontinued treatment due to adverse reactions. NORTH CHICAGO, Ill., Dec. 23, 2020 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today that the U.S. Food and Drug Administration (FDA) approved the update of the IMBRUVICA (ibrutinib) Prescribing Information to include efficacy and safety data for the combination of IMBRUVICA with rituximab for the treatment of Waldenstrm's macroglobulinemia (WM), based on the final analysis of the Phase . Distributed and Marketed by: Tell your healthcare provider if you are pregnant or think you may be pregnant during treatment with Imbruvica. Patients (n =529) were randomized 2:1 to receive either Imbruvica plus rituximab or FCR. Patients (n = 269) were randomized 1:1 to receive either Imbruvica 420 mg daily until disease progression or unacceptable toxicity, or chlorambucil at a starting dose of 0.5 mg/kg on Days 1 and 15 of each 28-day cycle for a maximum of 12 cycles, with an allowance for intrapatient dose increases up to 0.8 mg/kg based on tolerability. The median number of prior treatments was 4 (range, 1 to 7 treatments). Upon initiation of single-agent Imbruvica, an increase in lymphocyte counts (i.e., 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) occurred in 66% of patients in the CLL studies. Reduce recommended dose when administering Imbruvica to patients with total bilirubin level > 1.5 to 3 x ULN (unless of non-hepatic origin or due to Gilberts syndrome) [see Dosage and Administration (2.4)]. The INNOVATE study, a randomized, double-blind, placebo-controlled, phase 3 study of Imbruvica or placebo in combination with rituximab (NCT02165397), was conducted in treatment nave or previously treated patients with WM. Patients (n = 578) were randomized 1:1 to receive either Imbruvica 420 mg daily or placebo in combination with BR until disease progression, or unacceptable toxicity. 20070481 R2 With a median follow-up time on study 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. Discard after 60 Days. If you take too much Imbruvica call your healthcare provider or go to the nearest hospital emergency room right away. The median time since diagnosis was 80 months and the median number of prior treatments was 4 (range, 1 to 12 treatments). b Grading based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria, or International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for hematologic toxicities in CLL/SLL. Cardiac Arrhythmias, Cardiac Failure, and Sudden Death:Fatal and serious cardiac arrhythmias and cardiac failure have occurred with IMBRUVICA. Each 280 mg tablet is a purple oblong tablet debossed with ibr on one side and 280 on the other side. BR = bendamustine and rituximab; CI = confidence interval; HR = hazard ratio; NE = not evaluable. Hypertension occurred in 19% of 1,476 patients who received Imbruvica in clinical trials. Dose modifications of Imbruvica are recommended when used concomitantly with posaconazole, voriconazole and moderate CYP3A inhibitors [see Dosage and Administration (2.3)]. a Median OS not evaluable for either arm. The safety and effectiveness of Imbruvica have been established for treatment of cGVHD after failure of one or more lines of systemic therapy in pediatric patients 1 year of age and older. Flexibility to start patients at home 1*. The INNOVATE monotherapy arm included 31 patients with previously treated WM who failed prior rituximab-containing therapy and received single-agent Imbruvica. Fatal and non-fatal infections (including bacterial, viral, or fungal) have occurred with IMBRUVICA therapy. Animal Data. 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, Evaluate cardiac history and function at baseline, and monitor patients for cardiac arrhythmias and cardiac function. Do not open, break, or chew IMBRUVICA capsules. PRINCIPAL DISPLAY PANEL - 120 Capsule Bottle Label. All patients had a baseline ECOG performance status of 0 or 1. The onset of isolated lymphocytosis occurs during the first month of Imbruvica therapy and resolves by a median of 14 weeks (range, 0.1 to 104 weeks). Avoid the use of Imbruvica in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)]. 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. Agents administered in combination with IMBRUVICA require infusion. Effect of CYP3A Inhibitors on Ibrutinib: The coadministration of multiple doses of ketoconazole (strong CYP3A inhibitor) increased the Cmax of ibrutinib by 29-fold and AUC by 24-fold. At baseline, the median serum IgM value was 3.5 g/dL (range, 0.7 to 8.4 g/dL). Inform patients of the possibility of serious infection, and to report any signs or symptoms (fever, chills, weakness, confusion) suggestive of infection [see Warnings and Precautions (5.2)]. 140 mg. Each capsule contains: ibrutinib 140 mg Swallow capsules whole with water Swallow capsules whole with water, PRINCIPAL DISPLAY PANEL - 90 Capsule Bottle Carton, Each capsule contains: ibrutinib 140 mg 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 [see Dosage and Administration (2.2)]. Available for Android and iOS devices. Imbruvica may be taken as a single agent, or in combination with other agents. Cinar M, Hamedani F, Mo Z, et al. 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. No ramp-up dosing needed at therapy initiation hbbd```b`X"(c"x"^ D2`q'2,&Un0D2I@YvD2M "DD .`5 sAj= q%I2-FC{?S ]K Do not open, break, or chew the capsules. Adverse reactions and laboratory abnormalities described below in Table 9 and Table 10 reflect exposure to Imbruvica with a median duration of 8.6 months and exposure to ofatumumab with a median of 5.3 months in RESONATE in patients with previously treated CLL/SLL. Fludarabine was administered at a dose of 25 mg/m2, and cyclophosphamide was administered at a dose of 250 mg/m2, both on Days 1, 2, and 3 of Cycles 1-6. The RESONATE-2 study, a randomized, multicenter, open-label, phase 3 study of Imbruvica versus chlorambucil (NCT01722487), was conducted in patients with treatment nave CLL or SLL who were 65 years of age or older. All partial responses achieved; none of the patients achieved a complete response. Herman SEM, Gordon AL, Hertlein E, et al. b IRC evaluated. The primary endpoint in this study was investigator-assessed overall response rate (ORR). Take IMBRUVICA 1 time a day at about the same time each day. Products regulation Blood donation Lab services Who we are E-services. Each 420 mg tablet is a yellow green to green oblong tablet debossed with ibr on one side and 420 on the other side. Do not open, break, or chew IMBRUVICA capsules. Inform patients of the possibility of bleeding, and to report any signs or symptoms (severe headache, blood in stools or urine, prolonged or uncontrolled bleeding). Lactation: Take IMBRUVICA exactly as your healthcare provider tells you to take it. The administration of Imbruvica with a high-fat and high-calorie meal (800 calories to 1,000 calories with approximately 50% of total caloric content of the meal from fat) increased ibrutinib Cmax by 2- to 4-fold and AUC by approximately 2-fold, compared with administration of ibrutinib after overnight fasting. 2022 Pharmacyclics LLC 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. Ask your pharmacist how to properly dispose of the medicine. If you are able to become pregnant, your healthcare provider will do a pregnancy test before starting treatment with IMBRUVICA. Take your next dose of IMBRUVICA at your regular time on the next day. Serious adverse reactions occurred in 64% of patients who received Imbruvica. Based on data from 1,605 of these patients, the median time to first onset was 21 days (range, 0 to 708) versus 46 days (range, 0 to 492) for any grade diarrhea and 117 days (range, 3 to 414) versus 194 days (range, 11 to 325) for Grade 3 diarrhea in Imbruvica-treated patients compared to the control arm, respectively. Adverse reactions which resulted in permanent discontinuation in at least two patients included hemorrhage. Grade 3 or greater hypertension occurred in 8% of patients, 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, General disorders and administration site conditions, Musculoskeletal and connective tissue disorders, Respiratory, thoracic and mediastinal disorders, Injury, poisoning and procedural complications, General disorders and administrative site conditions, Respiratory, thoracic, and mediastinal disorders, Ibrutinib is kinase inhibitor. Daily for patients with SLL with: may affect how Imbruvica works by this. Was acquired by AbbVie in 2015 systemic therapies for cGVHD was permitted drug information, pills. To help reduce your risk of these events in milliliters ( mLs ) subdural hematoma ( 1.8 % which. 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