Data from FDA - Curated by Marshall Pearce - Last updated 09 August 2017

Indication(s)

1 INDICATIONS AND USAGE ORENCIA is a selective T cell costimulation modulator indicated for: Adult Rheumatoid Arthritis (RA) (1.1) •moderately to severely active RA in adults. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists (1.1). Juvenile Idiopathic Arthritis (1.2) •moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. ORENCIA may be used as monotherapy or concomitantly with methotrexate (1.2). Adult Psoriatic Arthritis (PsA) (1.3) •active PsA in adults. (1.3) Important Limitations of Use ( 1.4 ) •should not be given concomitantly with TNF antagonists (1.4, 5.1). 1.1 Adult Rheumatoid Arthritis (RA) ORENCIA® is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists. 1.2 Juvenile Idiopathic Arthritis ORENCIA is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX). 1.3 Adult Psoriatic Arthritis (PsA) ORENCIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA). 1.4 Important Limitations of Use ORENCIA should not be administered concomitantly with TNF antagonists. ORENCIA is not recommended for use concomitantly with other biologic rheumatoid arthritis (RA) therapy, such as anakinra.

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contraindications
4 CONTRAINDICATIONS None. •None (4)
Adverse reactions
6 ADVERSE REACTIONS Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not predict the rates observed in a broader patient population in clinical practice. As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to abatacept in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Most common adverse events (≥10%) are headache, upper respiratory tract infection, nasopharyngitis, and nausea (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience in Adult RA Patients Treated with Intravenous ORENCIA The data described herein reflect exposure to ORENCIA administered intravenously in patients with active RA in placebo-controlled studies (1955 patients with ORENCIA, 989 with placebo). The studies had either a double-blind, placebo-controlled period of 6 months (258 patients with ORENCIA, 133 with placebo) or 1 year (1697 patients with ORENCIA, 856 with placebo). A subset of these patients received concomitant biologic DMARD therapy, such as a TNF blocking agent (204 patients with ORENCIA, 134 with placebo). The majority of patients in RA clinical studies received one or more of the following concomitant medications with ORENCIA: methotrexate, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, TNF blocking agents, azathioprine, chloroquine, gold, hydroxychloroquine, leflunomide, sulfasalazine, and anakinra. The most serious adverse reactions were serious infections and malignancies. The most commonly reported adverse events (occurring in ≥10% of patients treated with ORENCIA) were headache, upper respiratory tract infection, nasopharyngitis, and nausea. The adverse events most frequently resulting in clinical intervention (interruption or discontinuation of ORENCIA) were due to infection. The most frequently reported infections resulting in dose interruption were upper respiratory tract infection (1.0%), bronchitis (0.7%), and herpes zoster (0.7%). The most frequent infections resulting in discontinuation were pneumonia (0.2%), localized infection (0.2%), and bronchitis (0.1%). Infections In the placebo-controlled trials, infections were reported in 54% of ORENCIA-treated patients and 48% of placebo-treated patients. The most commonly reported infections (reported in 5%-13% of patients) were upper respiratory tract infection, nasopharyngitis, sinusitis, urinary tract infection, influenza, and bronchitis. Other infections reported in fewer than 5% of patients at a higher frequency (>0.5%) with ORENCIA compared to placebo, were rhinitis, herpes simplex, and pneumonia [see Warnings and Precautions (5.3) ]. Serious infections were reported in 3.0% of patients treated with ORENCIA and 1.9% of patients treated with placebo. The most common (0.2%-0.5%) serious infections reported with ORENCIA were pneumonia, cellulitis, urinary tract infection, bronchitis, diverticulitis, and acute pyelonephritis [see Warnings and Precautions (5.3) ]. Malignancies In the placebo-controlled portions of the clinical trials (1955 patients treated with ORENCIA for a median of 12 months), the overall frequencies of malignancies were similar in the ORENCIA- and placebo-treated patients (1.3% and 1.1%, respectively). However, more cases of lung cancer were observed in ORENCIA-treated patients (4, 0.2%) than placebo-treated patients (0). In the cumulative ORENCIA clinical trials (placebo-controlled and uncontrolled, open-label) a total of 8 cases of lung cancer (0.21 cases per 100 patient-years) and 4 lymphomas (0.10 cases per 100 patient-years) were observed in 2688 patients (3827 patient-years). The rate observed for lymphoma is approximately 3.5-fold higher than expected in an age- and gender-matched general population based on the National Cancer Institute's Surveillance, Epidemiology, and End Results Database. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. Other malignancies included skin, breast, bile duct, bladder, cervical, endometrial, lymphoma, melanoma, myelodysplastic syndrome, ovarian, prostate, renal, thyroid, and uterine cancers [see Warnings and Precautions (5.6) ]. The potential role of ORENCIA in the development of malignancies in humans is unknown. Infusion-Related Reactions and Hypersensitivity Reactions Acute infusion-related events (adverse reactions occurring within 1 hour of the start of the infusion) in Studies III, IV, and V [see Clinical Studies (14.1) ] were more common in the ORENCIA-treated patients than the placebo patients (9% for ORENCIA, 6% for placebo). The most frequently reported events (1%-2%) were dizziness, headache, and hypertension. Acute infusion-related events that were reported in >0.1% and ≤1% of patients treated with ORENCIA included cardiopulmonary symptoms, such as hypotension, increased blood pressure, and dyspnea; other symptoms included nausea, flushing, urticaria, cough, hypersensitivity, pruritus, rash, and wheezing. Most of these reactions were mild (68%) to moderate (28%). Fewer than 1% of ORENCIA-treated patients discontinued due to an acute infusion-related event. In controlled trials, 6 ORENCIA-treated patients compared to 2 placebo-treated patients discontinued study treatment due to acute infusion-related events. In clinical trials of 2688 adult RA patients treated with intravenous ORENCIA, there were two cases (<0.1%) of anaphylaxis or anaphylactoid reactions. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in less than 0.9% of ORENCIA-treated patients and generally occurred within 24 hours of ORENCIA infusion. Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction [see Warnings and Precautions (5.2) ]. Adverse Reactions in Patients with COPD In Study V [see Clinical Studies (14.1) ], there were 37 patients with chronic obstructive pulmonary disease (COPD) who were treated with ORENCIA and 17 COPD patients who were treated with placebo. The COPD patients treated with ORENCIA developed adverse events more frequently than those treated with placebo (97% vs 88%, respectively). Respiratory disorders occurred more frequently in ORENCIA-treated patients compared to placebo-treated patients (43% vs 24%, respectively) including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of ORENCIA-treated patients developed a serious adverse event compared to placebo-treated patients (27% vs 6%), including COPD exacerbation (3 of 37 patients [8%]) and pneumonia (1 of 37 patients [3%]) [see Warnings and Precautions (5.5) ]. Other Adverse Reactions Adverse events occurring in 3% or more of patients and at least 1% more frequently in ORENCIA-treated patients during placebo-controlled RA studies are summarized in Table 3. Table 3: Adverse Events Occurring in 3% or More of Patients and at Least 1% More Frequently in ORENCIA-Treated Patients During Placebo-Controlled RA Studies Adverse Event (Preferred Term) ORENCIA (n=1955)a Percentage Placebo (n=989)b Percentage a Includes 204 patients on concomitant biologic DMARDs (adalimumab, anakinra, etanercept, or infliximab). b Includes 134 patients on concomitant biologic DMARDs (adalimumab, anakinra, etanercept, or infliximab). Headache 18 13 Nasopharyngitis 12 9 Dizziness 9 7 Cough 8 7 Back pain 7 6 Hypertension 7 4 Dyspepsia 6 4 Urinary tract infection 6 5 Rash 4 3 Pain in extremity 3 2 Immunogenicity Antibodies directed against the entire abatacept molecule or to the CTLA-4 portion of abatacept were assessed by ELISA assays in RA patients for up to 2 years following repeated treatment with ORENCIA. Thirty-four of 1993 (1.7%) patients developed binding antibodies to the entire abatacept molecule or to the CTLA-4 portion of abatacept. Because trough levels of abatacept can interfere with assay results, a subset analysis was performed. In this analysis it was observed that 9 of 154 (5.8%) patients that had discontinued treatment with ORENCIA for over 56 days developed antibodies. Samples with confirmed binding activity to CTLA-4 were assessed for the presence of neutralizing antibodies in a cell-based luciferase reporter assay. Six of 9 (67%) evaluable patients were shown to possess neutralizing antibodies. However, the development of neutralizing antibodies may be underreported due to lack of assay sensitivity. No correlation of antibody development to clinical response or adverse events was observed. The data reflect the percentage of patients whose test results were positive for antibodies to abatacept in specific assays. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to abatacept with the incidence of antibodies to other products may be misleading. Clinical Experience in Methotrexate-Naive Patients Study VI was an active-controlled clinical trial in methotrexate-naive patients [see Clinical Studies (14.1) ]. The safety experience in these patients was consistent with Studies I-V. 6.2 Clinical Studies Experience in Adult RA Patients Treated with Subcutaneous ORENCIA Study SC-1 was a randomized, double-blind, double-dummy, non-inferiority study that compared the efficacy and safety of abatacept administered subcutaneously (SC) and intravenously (IV) in 1457 subjects with rheumatoid arthritis, receiving background methotrexate, and experiencing an inadequate response to methotrexate (MTX-IR) [see Clinical Studies (14.1) ]. The safety experience and immunogenicity for ORENCIA administered subcutaneously was consistent with intravenous Studies I-VI. Due to the route of administration, injection site reactions and immunogenicity were evaluated in Study SC-1 and two other smaller studies discussed in the sections below. Injection Site Reactions in Adult RA Patients Treated with Subcutaneous ORENCIA Study SC-1 compared the safety of abatacept including injection site reactions following subcutaneous or intravenous administration. The overall frequency of injection site reactions was 2.6% (19/736) and 2.5% (18/721) for the subcutaneous abatacept group and the intravenous abatacept group (subcutaneous placebo), respectively. All these injection site reactions (including hematoma, pruritus, and erythema) were mild (83%) to moderate (17%) in severity, and none necessitated drug discontinuation. Immunogenicity in Adult RA Patients Treated with Subcutaneous ORENCIA Study SC-1 compared the immunogenicity to abatacept following subcutaneous or intravenous administration. The overall immunogenicity frequency to abatacept was 1.1% (8/725) and 2.3% (16/710) for the subcutaneous and intravenous groups, respectively. The rate is consistent with previous experience, and there was no correlation of immunogenicity with effects on pharmacokinetics, safety, or efficacy. Immunogenicity and Safety of Subcutaneous ORENCIA Administration as Monotherapy without an Intravenous Loading Dose Study SC-2 was conducted to determine the effect of monotherapy use of ORENCIA on immunogenicity following subcutaneous administration without an intravenous load in 100 RA patients, who had not previously received abatacept or other CTLA4Ig, who received either subcutaneous ORENCIA plus methotrexate (n=51) or subcutaneous ORENCIA monotherapy (n=49). No patients in either group developed anti-product antibodies after 4 months of treatment. The safety observed in this study was consistent with that observed in the other subcutaneous studies. Immunogenicity and Safety of Subcutaneous ORENCIA upon Withdrawal (Three Months) and Restart of Treatment Study SC-3 in the subcutaneous program was conducted to investigate the effect of withdrawal (three months) and restart of ORENCIA subcutaneous treatment on immunogenicity in RA patients treated concomitantly with methotrexate. One hundred sixty-seven patients were enrolled in the first 3-month treatment period and responders (n=120) were randomized to either subcutaneous ORENCIA or placebo for the second 3-month period (withdrawal period). Patients from this period then received open-label ORENCIA treatment in the final 3-month period of the study (period 3). At the end of the withdrawal period, 0/38 patients who continued to receive subcutaneous ORENCIA developed anti-product antibodies compared to 7/73 (9.6%) of patients who had subcutaneous ORENCIA withdrawn during this period. Half of the patients receiving subcutaneous placebo during the withdrawal period received a single intravenous infusion of ORENCIA at the start of period 3 and half received intravenous placebo. At the end of period 3, when all patients again received subcutaneous ORENCIA, the immunogenicity rates were 1/38 (2.6%) in the group receiving subcutaneous ORENCIA throughout, and 2/73 (2.7%) in the group that had received placebo during the withdrawal period. Upon reinitiating therapy, there were no injection reactions and no differences in response to therapy in patients who were withdrawn from subcutaneous therapy for up to 3 months relative to those who remained on subcutaneous therapy, whether therapy was reintroduced with or without an intravenous loading dose. The safety observed in this study was consistent with that observed in the other studies. 6.3 Clinical Studies Experience in Juvenile Idiopathic Arthritis Patients Treated with Intravenous ORENCIA In general, the adverse events in pediatric patients were similar in frequency and type to those seen in adult patients [see Warnings and Precautions (5) , Adverse Reactions (6) ]. Study JIA-1 was a three-part study including an open-label extension that assessed the safety and efficacy of intravenous ORENCIA in 190 pediatric patients, 6 to 17 years of age, with polyarticular juvenile idiopathic arthritis. Overall frequency of adverse events in the 4-month, lead-in, open-label period of the study was 70%; infections occurred at a frequency of 36% [see Clinical Studies (14.2) ]. The most common infections were upper respiratory tract infection and nasopharyngitis. The infections resolved without sequelae, and the types of infections were consistent with those commonly seen in outpatient pediatric populations. Other events that occurred at a prevalence of at least 5% were headache, nausea, diarrhea, cough, pyrexia, and abdominal pain. A total of 6 serious adverse events (acute lymphocytic leukemia, ovarian cyst, varicella infection, disease flare [2], and joint wear) were reported during the initial 4 months of treatment with ORENCIA. Of the 190 patients with juvenile idiopathic arthritis treated with ORENCIA in clinical trials, there was one case of a hypersensitivity reaction (0.5%). During Periods A, B, and C, acute infusion-related reactions occurred at a frequency of 4%, 2%, and 3%, respectively, and were consistent with the types of events reported in adults. Upon continued treatment in the open-label extension period, the types of adverse events were similar in frequency and type to those seen in adult patients, except for a single patient diagnosed with multiple sclerosis while on open-label treatment. Immunogenicity Antibodies directed against the entire abatacept molecule or to the CTLA-4 portion of abatacept were assessed by ELISA assays in patients with juvenile idiopathic arthritis following repeated treatment with ORENCIA throughout the open-label period. For patients who were withdrawn from therapy for up to 6 months during the double-blind period, the rate of antibody formation to the CTLA-4 portion of the molecule was 41% (22/54), while for those who remained on therapy the rate was 13% (7/54). Twenty of these patients had samples that could be tested for antibodies with neutralizing activity; of these, 8 (40%) patients were shown to possess neutralizing antibodies. The presence of antibodies was generally transient and titers were low. The presence of antibodies was not associated with adverse events, changes in efficacy, or an effect on serum concentrations of abatacept. For patients who were withdrawn from ORENCIA during the double-blind period for up to 6 months, no serious acute infusion-related events were observed upon re-initiation of ORENCIA therapy. 6.4 Clinical Studies Experience in Juvenile Idiopathic Arthritis Patients Treated with Subcutaneous ORENCIA Study JIA-2 was an open-label study with a 4-month short-term period and a long-term extension period that assessed the pharmacokinetics (PK), safety, and efficacy of subcutaneous ORENCIA in 205 pediatric patients, 2 to 17 years of age with juvenile idiopathic arthritis. The safety experience and immunogenicity for ORENCIA administered subcutaneously were consistent with the intravenous Study JIA-1. There were no reported cases of hypersensitivity reactions. Local injection-site reactions occurred at a frequency of 4.4%. 6.5 Clinical Studies Experience in Adult PsA Patients The safety of ORENCIA was evaluated in 594 patients with psoriatic arthritis (341 patients on ORENCIA and 253 patients on placebo), in two randomized, double-blind, placebo-controlled trials. Of the 341 patients who received ORENCIA, 128 patients received intravenous ORENCIA (PsA-I) and 213 patients received subcutaneous ORENCIA (PsA-II). The safety profile was comparable between studies PsA-I and PsA-II and consistent with the safety profile in rheumatoid arthritis [see Warnings and Precautions (5), Adverse Reactions (6.1 , 6.2) ]. 6.6 Postmarketing Experience Adverse reactions have been reported during the postapproval use of ORENCIA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to ORENCIA. Based on the postmarketing experience in adult RA patients, the following adverse reaction has been identified during postapproval use with ORENCIA. •Vasculitis (including cutaneous vasculitis and leukocytoclastic vasculitis)

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION Intravenous Administration for Adult RA (2.1) and Adult PsA (2.3) Body Weight of Patient Dose Number of Vials Less than 60 kg 500 mg 2 60 to 100 kg 750 mg 3 More than 100 kg 1000 mg 4 Subcutaneous Administration for Adult RA (2.1) •Administer by subcutaneous injection once weekly with or without an intravenous loading dose. For patients initiating therapy with an intravenous loading dose, administer a single intravenous infusion (as per body weight categories above), followed by the first 125 mg subcutaneous injection given within a day of the intravenous infusion. •Patients transitioning from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose. Intravenous Administration for Juvenile Idiopathic Arthritis (2.2) •Pediatric patients weighing less than 75 kg receive 10 mg/kg intravenously based on the patient's body weight. Pediatric patients weighing 75 kg or more should be administered ORENCIA following the adult intravenous dosing regimen, not to exceed a maximum dose of 1000 mg. Intravenous dosing has not been studied in patients younger than 6 years of age. (2.2) Subcutaneous Administration for Juvenile Idiopathic Arthritis (2.2) Body Weight of Patient Dose (once weekly) 10 to less than 25 kg 50 mg 25 to less than 50 kg 87.5 mg 50 kg or more 125 mg Subcutaneous Administration for Adult PsA (2.3) •Administer by subcutaneous injection once weekly without the need of an intravenous loading dose. •Patients transitioning from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose. General Dosing Information for Intravenous Administration (2.1 and 2.3) •Administer as a 30-minute intravenous infusion (2.1, 2.2) •Following initial dose, give at 2 and 4 weeks, then every 4 weeks (2.1) •Prepare ORENCIA using only the silicone-free disposable syringe (2.3) •Use only Sterile Water for Injection, USP to reconstitute the powder (2.3) •The reconstituted and diluted product must be administered using a filter (2.3) 2.1 Adult Rheumatoid Arthritis For adult patients with RA, ORENCIA may be administered as an intravenous infusion or as a subcutaneous injection. ORENCIA may be used as monotherapy or concomitantly with DMARDs other than TNF antagonists. Intravenous Dosing Regimen ORENCIA lyophilized powder should be reconstituted and administered after dilution [see Dosage and Administration (2.3) ] as a 30-minute intravenous infusion utilizing the weight range-based dosing specified in Table 1. Following the initial intravenous administration, an intravenous infusion should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. Table 1: Dose of ORENCIA for Intravenous Infusion in Adult RA Patients Body Weight of Patient Dose Number of Vialsa a Each vial provides 250 mg of abatacept for administration. Less than 60 kg 500 mg 2 60 to 100 kg 750 mg 3 More than 100 kg 1000 mg 4 Subcutaneous Dosing Regimen ORENCIA 125 mg in prefilled syringes or in ORENCIA ClickJect™ autoinjector should be administered by subcutaneous injection once weekly [see Dosage and Administration (2.4) ] and may be initiated with or without an intravenous loading dose. For patients initiating therapy with an intravenous loading dose, ORENCIA should be initiated with a single intravenous infusion (as per body weight categories listed in Table 1), followed by the first 125 mg subcutaneous injection administered within a day of the intravenous infusion. Patients transitioning from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose. 2.2 Juvenile Idiopathic Arthritis For patients with juvenile idiopathic arthritis (JIA), ORENCIA may be administered as an intravenous infusion (6 years of age and older) or a subcutaneous injection (2 years of age and older). Intravenous dosing has not been studied in patients younger than 6 years of age. ORENCIA may be used as monotherapy or concomitantly with methotrexate. Intravenous Dosing Regimen ORENCIA should be administered as a 30-minute intravenous infusion based on body weight. Pediatric patients with: •body weight less than 75 kg should be administered ORENCIA at a dose of 10 mg/kg [see Dosage and Administration (2.3) ]. •body weight of 75 kg or more should be administered ORENCIA following the adult intravenous dosing regimen (see Table 1), not to exceed a maximum dose of 1000 mg. Following the initial administration, ORENCIA should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. Any unused portions in the vials must be immediately discarded. Subcutaneous Dosing Regimen ORENCIA for subcutaneous injection should be initiated without an intravenous loading dose and be administered utilizing the weight range-based dosing as specified in Table 2. Table 2: Dose of ORENCIA for Subcutaneous Administration in Patients 2 Years of Age or Older with JIA Body Weight of Patient Dose (once weekly) 10 to less than 25 kg 50 mg 25 to less than 50 kg 87.5 mg 50 kg or more 125 mg The safety and efficacy of ORENCIA ClickJect autoinjector for subcutaneous injection has not been studied in patients under 18 years of age. 2.3 Adult Psoriatic Arthritis For adult patients with psoriatic arthritis, ORENCIA may be administered as an intravenous infusion (IV) or a subcutaneous (SC) injection. ORENCIA can be used with or without non-biologic DMARDs. Intravenous Dosing Regimen ORENCIA IV should be administered as a 30-minute intravenous infusion utilizing the weight range-based dosing specified in Table 1. Following the initial intravenous administration, an intravenous infusion should be given at 2 and 4 weeks after the first infusion and every 4 weeks thereafter. Subcutaneous Dosing Regimen ORENCIA SC 125 mg should be administered by subcutaneous injection once weekly without the need for an intravenous loading dose. Patients switching from ORENCIA intravenous therapy to subcutaneous administration should administer the first subcutaneous dose instead of the next scheduled intravenous dose. 2.4 Preparation and Administration Instructions for Intravenous Infusion Use aseptic technique. ORENCIA for Injection is provided as a lyophilized powder in preservative-free, single-use vials. Each ORENCIA vial provides 250 mg of abatacept for administration. The ORENCIA powder in each vial must be reconstituted with 10 mL of Sterile Water for Injection, USP, using only the silicone-free disposable syringe provided with each vial and an 18- to 21-gauge needle. After reconstitution, the concentration of abatacept in the vial will be 25 mg/mL. If the ORENCIA powder is accidentally reconstituted using a siliconized syringe, the solution may develop a few translucent particles. Discard any solutions prepared using siliconized syringes. If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe from inventory. For information on obtaining additional silicone-free disposable syringes , contact Bristol-Myers Squibb 1-800-ORENCIA. 1)Use 10 mL of Sterile Water for Injection, USP to reconstitute the ORENCIA powder. To reconstitute the ORENCIA powder, remove the flip-top from the vial and wipe the top with an alcohol swab. Insert the syringe needle into the vial through the center of the rubber stopper and direct the stream of Sterile Water for Injection, USP, to the glass wall of the vial. Do not use the vial if the vacuum is not present. Rotate the vial with gentle swirling to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation. 2)Upon complete dissolution of the lyophilized powder, the vial should be vented with a needle to dissipate any foam that may be present. After reconstitution, each milliliter will contain 25 mg (250 mg/10 mL). The solution should be clear and colorless to pale yellow. Do not use if opaque particles, discoloration, or other foreign particles are present. 3)The reconstituted ORENCIA solution must be further diluted to 100 mL as follows. From a 100 mL infusion bag or bottle, withdraw a volume of 0.9% Sodium Chloride Injection, USP, equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose. Slowly add the reconstituted ORENCIA solution into the infusion bag or bottle using the same silicone-free disposable syringe provided with each vial . Gently mix. Do not shake the bag or bottle . The final concentration of abatacept in the bag or bottle will depend upon the amount of drug added, but will be no more than 10 mg/mL. Any unused portions in the ORENCIA vial must be immediately discarded. 4)Prior to administration, the ORENCIA solution should be inspected visually for particulate matter and discoloration. Discard the solution if any particulate matter or discoloration is observed. 5)The entire, fully diluted ORENCIA solution should be administered over a period of 30 minutes and must be administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (pore size of 0.2 μm to 1.2 μm). 6)The infusion of the fully diluted ORENCIA solution must be completed within 24 hours of reconstitution of the ORENCIA vials. The fully diluted ORENCIA solution may be stored at room temperature or refrigerated at 2°C to 8°C (36°F to 46°F) before use. Discard the fully diluted solution if not administered within 24 hours. 7)ORENCIA should not be infused concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the coadministration of ORENCIA with other agents. 2.5 General Considerations for Subcutaneous Administration ORENCIA prefilled syringes and ORENCIA ClickJect autoinjectors are intended for subcutaneous use only and are not intended for intravenous infusion. ORENCIA prefilled syringes and ORENCIA ClickJect autoinjectors are intended for use under the guidance of a physician or healthcare practitioner. After proper training in subcutaneous injection technique, a patient or caregiver may inject with ORENCIA if a physician/healthcare practitioner determines that it is appropriate. Patients and caregivers should be instructed to follow the directions provided in the Instructions for Use for additional details on medication administration. Inspect visually for particulate matter and discoloration prior to administration. Do not use ORENCIA prefilled syringes or ORENCIA ClickJect autoinjectors exhibiting particulate matter or discoloration. ORENCIA should be clear and colorless to pale yellow. Patients using ORENCIA prefilled syringes and ORENCIA ClickJect autoinjectors for subcutaneous administration should be instructed to inject the full amount, which provides the proper dose of ORENCIA, according to the directions provided in the Instructions for Use. Injection sites should be rotated and injections should never be given into areas where the skin is tender, bruised, red, or hard.
Use in special populations
8 USE IN SPECIFIC POPULATIONS •Pregnancy: Registry available. The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk (8.1) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972. Risk Summary The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. In reproductive toxicology studies in rats and rabbits, no fetal malformations were observed with intravenous administration of ORENCIA during organogenesis at doses that produced exposures approximately 29 times the exposure at the maximum recommended human dose (MRHD) of 10 mg/kg/month on an AUC basis. However, in a pre- and postnatal development study in rats, ORENCIA altered immune function in female rats at 11 times the MRHD on an AUC basis. Data Human Data There are no adequate and well-controlled studies of ORENCIA use in pregnant women. The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. Animal Data Intravenous administration of abatacept during organogenesis to mice (10, 55, or 300 mg/kg/day), rats (10, 45, or 200 mg/kg/day), and rabbits (10, 45, or 200 mg/kg every 3 days) produced exposures in rats and rabbits that were approximately 29 times the MRHD on an AUC basis (at maternal doses of 200 mg/kg/day in rats and rabbits), and no embryotoxicity or fetal malformations were observed in any species. In a study of pre- and postnatal development in rats (10, 45, or 200 mg/kg every 3 days from gestation day 6 through lactation day 21), alterations in immune function in female offspring, consisting of a 9-fold increase in T-cell-dependent antibody response relative to controls on postnatal day (PND) 56 and thyroiditis in a single female pup on PND 112, occurred at approximately 11 times the MRHD on an AUC basis (at a maternal dose of 200 mg/kg). No adverse effects were observed at approximately 3 times the MRHD (a maternal dose of 45 mg/kg). It is not known if immunologic perturbations in rats are relevant indicators of a risk for development of autoimmune diseases in humans exposed in utero to abatacept. Exposure to abatacept in the juvenile rat, which may be more representative of the fetal immune system state in the human, resulted in immune system abnormalities including inflammation of the thyroid and pancreas [see Nonclinical Toxicology (13.2) ]. 8.2 Lactation Risk Summary There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept. 8.4 Pediatric Use In Study JIA-1, ORENCIA with intravenous administration was shown to reduce signs and symptoms of active polyarticular JIA in patients 6 to 17 years of age [see Clinical Studies (14.2) ]. ORENCIA with intravenous administration has not been studied in patients younger than 6 years of age. In Study JIA-2, the PK and safety of ORENCIA prefilled syringe for subcutaneous injection have been studied in patients 2 to 17 years of age. The efficacy of ORENCIA for subcutaneous injection in children 2 to 17 years of age is based on pharmacokinetic exposure and extrapolation of established efficacy of intravenous ORENCIA in polyarticular JIA patients and subcutaneous ORENCIA in patients with RA [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ]. The safety and immunogenicity of ORENCIA for subcutaneous injection in children 2 to 17 years of age were assessed descriptively [see Adverse Reactions (6.4) ]. ORENCIA may be used as monotherapy or concomitantly with methotrexate. The safety and efficacy of ORENCIA ClickJect autoinjector for subcutaneous injection have not been studied in patients under 18 years of age. Studies in juvenile rats exposed to ORENCIA prior to immune system maturity have shown immune system abnormalities including an increase in the incidence of infections leading to death as well as inflammation of the thyroid and pancreas [see Nonclinical Toxicology (13.2) ]. Studies in adult mice and monkeys have not demonstrated similar findings. As the immune system of the rat is undeveloped in the first few weeks after birth, the relevance of these results to humans is unknown. The safety and efficacy of ORENCIA in pediatric patients for uses other than juvenile idiopathic arthritis have not been established. It is unknown if abatacept can cross the placenta into the fetus when the woman is treated with abatacept during pregnancy. Since abatacept is an immunomodulatory agent, the safety of administering live vaccines in infants exposed in utero to abatacept is unknown. Risk and benefits should be considered prior to vaccinating such infants. 8.5 Geriatric Use A total of 323 patients 65 years of age and older, including 53 patients 75 years and older, received ORENCIA in clinical studies. No overall differences in safety or effectiveness were observed between these patients and younger patients, but these numbers are too low to rule out differences. The frequency of serious infection and malignancy among ORENCIA-treated patients over age 65 was higher than for those under age 65. Because there is a higher incidence of infections and malignancies in the elderly population in general, caution should be used when treating the elderly.

Interactions

7 DRUG INTERACTIONS 7.1 TNF Antagonists Concurrent administration of a TNF antagonist with ORENCIA has been associated with an increased risk of serious infections and no significant additional efficacy over use of the TNF antagonists alone. Concurrent therapy with ORENCIA and TNF antagonists is not recommended [see Warnings and Precautions (5.1) ]. 7.2 Other Biologic RA Therapy There is insufficient experience to assess the safety and efficacy of ORENCIA administered concurrently with other biologic RA therapy, such as anakinra, and therefore such use is not recommended. 7.3 Blood Glucose Testing Parenteral drug products containing maltose can interfere with the readings of blood glucose monitors that use test strips with glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). The GDH-PQQ based glucose monitoring systems may react with the maltose present in ORENCIA for intravenous administration, resulting in falsely elevated blood glucose readings on the day of infusion. When receiving ORENCIA through intravenous administration, patients that require blood glucose monitoring should be advised to consider methods that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase test methods. ORENCIA for subcutaneous administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

More information

Category Value
Authorisation number BLA125118
Agency product number 7D0YB67S97
Orphan designation No
Product NDC 0003-2814,0003-2188,0003-2818,0003-2187
Date Last Revised 30-06-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 616015
Storage and handling Storage ORENCIA lyophilized powder supplied in a vial should be refrigerated at 2°C to 8°C (36°F to 46°F). Do not use beyond the expiration date on the vial. Protect the vials from light by storing in the original package until time of use. ORENCIA solution supplied in a prefilled syringe or ClickJect autoinjector should be refrigerated at 2°C to 8°C (36°F to 46°F). Do not use beyond the expiration date on the prefilled syringe or autoinjector. Protect from light by storing in the original package until time of use. Do not allow the prefilled syringe or autoinjector to freeze.
Marketing authorisation holder E.R. Squibb & Sons, L.L.C.