ORENCIA abatacept 125 mg/mL Injection, Solution, 4 syringes
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Selective T Cell Costimulation Modulator class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Abatacept is used: alone or in combination with other medications to reduce the pain, swelling, difficulty with daily activities, and joint damage caused by rheumatoid arthritis (a condition in which the body attacks its own joints causing pain, swelling, and loss of function) in adults who have not been helped by other medications. alone or in combination with methotrexate (Otrexup, Rasuvo, Reditrex, Trexall, Xatmep) to treat polyarticular juvenile idiopathic arthritis (PJIA; a type of childhood arthritis that affects five or more joints during the first six months of the condition, causin...
Read the full MedlinePlus article ↗- Orencia targets overactive immune cells called T cells, which are partly responsible for the inflammation that damages your joints in rheumatoid arthritis and psoriatic arthritis....
- What is Orencia actually doing to help my arthritis?
- That's a real and important concern. Because Orencia calms down part of your immune system, your body may have a harder time fighting off infections. Common ones like colds and uri...
- Should I be worried about getting infections while on this medicine?
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with abatacept — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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8 mg / 1 mL
UNII LQA7B6G8JG
A synthetic polymer made by combining water-soluble compounds. It acts as a surfactant and solubilizer to help mix oil and water-based ingredients, improving the medicine's texture and how active ingredients dissolve.
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0.838 mg / 1 mL
UNII 22ADO53M6F
A mineral salt derived from phosphoric acid, used as a buffer to maintain the pH balance of the medication and help stabilize the active ingredients.
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0.286 mg / 1 mL
UNII 3980JIH2SW
A salt form of phosphoric acid that acts as a buffer and pH adjuster in medicines. It helps keep the product at the correct acidity level for stability and effectiveness.
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170 mg / 1 mL
UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1,468.740 | $5,874.96 / 4 ml |
| Medicaid paysCMS SDUD · 12 mo | $1,473.26 | $5,893.04 / 4 ml |
| Medicare drug plans payPart D · Q2 2026 | $1,450.76 | $5,803.05 / 4 ml |
| Medicare Part B allowsASP · J0129 | $45.859 / J0129 unit | — |
Where does this data come from?
🧾 Billing & reimbursement
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Orencia 125 mg/mLthis 00003-2188-11 | E.R. | 4 syringes | $1,468.740 | — | Availability likely | — |
Where does this data come from?
⏳ Availability & biosimilar status
Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 00003-2188-11 You're viewing this | 4 SYRINGE, GLASS in 1 CARTON (0003-2188-11) / 1 mL in 1 SYRINGE, GLASS | $1,468.74 / mL | $5,874.96 | 2013-10-01 | Active |
| 00003-2188-21 | 1 SYRINGE, GLASS in 1 CARTON (0003-2188-21) / 1 mL in 1 SYRINGE, GLASS | — | — | 2013-10-01 | Discontinued by firm |
| 00003-2188-50 | 1 SYRINGE, GLASS in 1 CARTON (0003-2188-50) / 1 mL in 1 SYRINGE, GLASS | — | — | 2016-07-05 | Discontinued by firm |
| 00003-2188-51 | 4 SYRINGE, GLASS in 1 CARTON (0003-2188-51) / 1 mL in 1 SYRINGE, GLASS | $1,470.24 / mL | $5,880.96 | 2016-06-07 | Active |
| 00003-2188-90 | 1 SYRINGE, GLASS in 1 CARTON (0003-2188-90) / 1 mL in 1 SYRINGE, GLASS | — | — | 2016-07-12 | Active |
| 00003-2188-91 | 1 SYRINGE, GLASS in 1 CARTON (0003-2188-91) / 1 mL in 1 SYRINGE, GLASS | — | — | 2013-10-01 | Active |
This pack has the lowest per-mL cost of the 2 priced pack sizes ($1,468.74 NADAC).
This pack accounts for about 13% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓
Pack size FAQ
What quantity is in NDC 00003-2188-11?
What is the difference between NDC 00003-2188-11 and NDC 00003-2188-21?
What NDC number is used to bill for this package of ORENCIA abatacept 125 mg/mL Injection, Solution?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ORENCIA is a selective T cell costimulation modulator indicated for: • the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). (1.1) • the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA). (1.2) • the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
(1.3) • the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor. (1.4) Limitations of Use: Concomitant use of ORENCIA with other immunosuppressives [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended. ( 1.5 , 5.1)
1.1Adult Rheumatoid Arthritis ORENCIA ® is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
1.2Polyarticular Juvenile Idiopathic Arthritis ORENCIA is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).
1.3Psoriatic Arthritis ORENCIA is indicated for the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
1.4Prophylaxis for Acute Graft versus Host Disease ORENCIA is indicated for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.
1.5Limitations of Use The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDs), Janus kinase (JAK) inhibitors] is not recommended.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Intravenous Use for Adult RA (2.1) and Adult PsA (2.3) • Administer at 0, 2, and 4 weeks, and every 4 weeks thereafter, as a 30-minute infusion 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 1,000 mg 4 Subcutaneous Use for Adult RA (2.1) • Prior to the first subcutaneous dose, may administer an optional loading dose as a single intravenous infusion as per body weight categories above. • Administer 125 mg by subcutaneous injection once weekly (within a day of the intravenous infusion if infusion given). • Patients switching from intravenous use to subcutaneous use, administer first subcutaneous dose instead of next scheduled intravenous dose.
Intravenous Use for pJIA in Pediatric Patients ≥6 Years Old (2.2) • Pediatric patients weighing <75 kg administer 10 mg/kg intravenously and those weighing ≥75 kg administer the adult intravenous dosing regimen (not to exceed a maximum dose of 1,000 mg), as a 30-minute infusion. • Subsequently administer infusions at 2 and 4 weeks and every 4 weeks thereafter. Subcutaneous Use for pJIA and PsA in Pediatric Patients ≥2 Years Old (2.2) • Administer subcutaneously without an intravenous loading dose Body Weight of Pediatric Patient Dose (once weekly) 10 kg to less than 25 kg 50 mg 25 kg to less than 50 kg 87.5 mg 50 kg or more 125 mg Subcutaneous Use for Adult PsA ( 2.3 ) • Administer 125 mg by subcutaneous injection once weekly without an intravenous loading dose. • Patients switching from intravenous use to subcutaneous use, administer first subcutaneous dose instead of next scheduled intravenous dose.
Intravenous Use for Prophylaxis of aGVHD (2.4) • For patients 6 years and older, administer at a 10 mg/kg dose (maximum dose 1,000 mg) as a 60-minute infusion on the day before transplantation, followed by a dose on Day 5, 14, and 28 after transplant. • For patients 2 to less than 6 years old, administer a 15 mg/kg dose as a 60-minute infusion on the day before transplantation, followed by a 12 mg/kg dose as a 60-minute infusion on Day 5, 14, and 28 after transplant. Preparation and Administration Instructions ( 2.5 , 2.6 ) • Administer as a 30-minute intravenous infusion for RA, pJIA, and adult PsA.
(2.5) • Administer as a 60-minute intravenous infusion for aGVHD prophylaxis. (2.5) • See the Full Prescribing Information for preparation and administration instructions for intravenous infusion and recommendations for subcutaneous use. (2.5, 2.6) Prepare ORENCIA using only the silicone-free disposable syringe.
(2.5)
2.1Dosage in Adult Rheumatoid Arthritis For adult patients with RA, administer as an intravenous infusion or as a subcutaneous injection. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than JAK inhibitors or bDMARDs (e.g., TNF antagonists). Intravenous Dosage Reconstitute ORENCIA lyophilized powder and administer after dilution [see Dosage and Administration (2.5) ] as a 30-minute intravenous infusion utilizing the weight range-based dosing recommended in Table 1.
Following the initial intravenous infusion, administer as an intravenous infusion at 2 and 4 weeks and every 4 weeks thereafter. Table 1: Dose of ORENCIA for Intravenous Infusion in Adult RA Patients Body Weight of Adult Patient Dose Number of Vials a 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 1,000 mg 4 Subcutaneous Dosage Prior to the first subcutaneous dose, an optional loading dose may be administered as a single intravenous infusion (as per body weight categories in Table 1).
If an intravenous loading dose is used, administer the first subcutaneous injection within one day of the infusion. Administer ORENCIA 125 mg in prefilled syringes or in ORENCIA ClickJect™ autoinjector by subcutaneous injection once weekly [see Dosage and Administration (2.6) ] . For patients switching from ORENCIA…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Intravenous Infusion • For injection: 250 mg lyophilized powder in a single-dose vial. (3) Subcutaneous Use • Injection: 50 mg/0.4 mL, 87.5 mg/0.7 mL, 125 mg/mL solution in single-dose prefilled syringe. (3) • Injection: 125 mg/mL solution in a single-dose prefilled ClickJect™ autoinjectors.
(3) • Intravenous Infusion For injection: 250 mg white lyophilized powder in a single-dose vial [see Dosage and Administration (2.1 , 2.2 , 2.3 , 2.5 )] . • Subcutaneous Use Injection: 50 mg/0.4 mL, 87.5 mg/0.7 mL, and 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled glass syringe. Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector.
• Intravenous Infusion For injection: 250 mg white lyophilized powder in a single-dose vial [see Dosage and Administration (2.1 , 2.2 , 2.3 , 2.5 )] . • Subcutaneous Use Injection: 50 mg/0.4 mL, 87.5 mg/0.7 mL, and 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled glass syringe. Injection: 125 mg/mL of a clear to slightly opalescent, colorless to pale-yellow solution in a single-dose prefilled ClickJect autoinjector.
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Concomitant use with a TNF antagonist can increase the risk of infections and serious infections. (5.1) • Hypersensitivity and anaphylaxis have occurred. (5.2) • Serious infections reported.
Patients with a history of recurrent infections or underlying conditions predisposing to infections may experience more infections. Discontinue if a serious infection develops. (5.3) • Screen for latent TB infection prior to initiating therapy.
Patients testing positive should be treated prior to initiating ORENCIA. (5.3) • Screen for viral hepatitis prior to initiating ORENCIA. (5.3) • Update vaccinations prior to initiating ORENCIA.
Live vaccines should not be given concurrently or within 3 months of discontinuation. ORENCIA may blunt the effectiveness of some immunizations. (5.4) • COPD patients may develop more frequent respiratory adverse reactions.
(5.5) • Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation in patients treated for aGVHD prophylaxis. (5.7)
5.1Increased Risk of Infection with Concomitant Use of TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors In controlled clinical trials in patients with adult RA, patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs. 43%) and serious infections (4.4% vs. 0.8%) compared to patients treated with only TNF antagonists [see Adverse Reactions (6.1) ] .
These trials failed to demonstrate an important enhancement of efficacy with concomitant administration of ORENCIA with TNF antagonists; therefore, concurrent therapy with ORENCIA and a TNF antagonist is not recommended. While transitioning from TNF antagonist therapy to ORENCIA therapy, patients should be monitored for signs of infection. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.
5.2Hypersensitivity Reactions In clinical trials of 2688 adult RA patients treated with intravenous ORENCIA, there were two cases (<0.1%) of anaphylaxis 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. Of the 190 ORENCIA-treated patients in pJIA clinical trials, there was one case of a hypersensitivity reaction (0.5%) [see Adverse Reactions (6.1 )] .
In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days).
Appropriate medical support measures for the treatment of hypersensitivity reactions should be available for immediate use in the event of a reaction. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately with appropriate therapy instituted, and the use of ORENCIA should be permanently discontinued.
5.3Infections Serious infections, including sepsis and pneumonia, have been reported in patients receiving ORENCIA (serious infections were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively) [see Adverse Reactions (6.1) ] . Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which in addition to their underlying disease, could further predispose them to infection.
A higher rate of serious infections has been observed in adult RA patients treated with concurrent TNF antagonists and ORENCIA compared to those treated with ORENCIA alone [see Warnings and Precautions (5.1) ] . Healthcare providers should exercise caution when considering the use of ORENCIA in patients with a history of recurrent infections,…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors [see Warnings and Precautions (5.1) ] • Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] • Infections [see Warnings and Precautions (5.3) ] • Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD) [see Warnings and Precautions (5.5) ] • Immunosuppression [see Warnings and Precautions (5.6) ] • Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT) [see Warnings and Precautions (5.7) ] • Most common adverse events (≥10%) in RA are headache, upper respiratory tract infection, nasopharyngitis, and nausea.
(6.1) • Most common adverse reactions (≥10%) in prophylaxis of aGVHD are anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury. (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 .
6.1Clinical Trials Experience 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. Adverse Reactions in Adult Patients with RA Adverse Reactions in Adult Patients with RA Treated with Intravenous ORENCIA The data from placebo-controlled studies described herein reflect exposure to ORENCIA administered intravenously in patients with active RA (1955 patients with ORENCIA, 989 with placebo) (Studies I through VI) [see Clinical Studies (14.1) ] .
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 antagonist (204 patients with ORENCIA, 134 with placebo). The concomitant use of ORENCIA with a TNF antagonist is not recommended [see Indications and Usage (1.5) ] .
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 antagonist, 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 reactions 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%), 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%).
Most Common Adverse Reactions in Adult Patients with RA Treated with Intravenous ORENCIA Adverse reactions occurring in 3% or more of patients and at least 1% more frequently in ORENCIA-treated patients (intravenous) during placebo-controlled RA studies are summarized in Table 4. Table 4: Most Common Adverse Reactions* During Placebo-Controlled RA Studies of Intravenous ORENCIA Intravenous ORENCIA (n=1955) a Placebo (n=989) b * Occurred in ≥3% patients and >1% more frequently in ORENCIA-treated patients. a Includes 204 patients on concomitant biologic DMARDs (adalimumab, anakinra, etaner…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Immunosuppressants Concomitant 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) ]. There is insufficient experience to assess the safety and efficacy of ORENCIA administered concurrently with other biologic RA therapy, such as anakinra, or other biologic PsA therapy, and JAK inhibitors and therefore such use is not recommended. [see Warnings and Precautions (5.1) ] .
7.2Blood 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 intravenous ORENCIA, 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.
🔄 Drug / Laboratory Test Interactions ▾
7.2Blood 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 intravenous ORENCIA, 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. However, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while in utero (see Clinical Considerations) . 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. Clinical Considerations Infants and Administration of Live Vaccines It is unknown if abatacept can cross the placenta into the fetus when a woman is treated with ORENCIA during pregnancy. Abatacept is an immunomodulatory agent.
It is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants [see Warnings and Precautions (5.4) ] . 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) ] .
8.2Lactation 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.
8.4Pediatric Use Polyarticular Juvenile Idiopathic Arthritis The safety and effectiveness of ORENCIA for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA) have been established (ORENCIA may be used as monotherapy or concomitantly with methotrexate). Use of ORENCIA for this indication is supported by evidence from the following studies: Intravenous Use : A randomized withdrawal efficacy, safety, and pharmacokinetic study of intravenous ORENCIA in 190 pediatric patients 6 to 17 years of age with pJIA [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] .
Given that population pharmacokinetic (PK) analyses (after intravenous ORENCIA administration) showed that clearance of abatacept increased with baseline body weight, intravenous ORENCIA is administered either weight-based or weight…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary The data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. However, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while in utero (see Clinical Considerations) . 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. Clinical Considerations Infants and Administration of Live Vaccines It is unknown if abatacept can cross the placenta into the fetus when a woman is treated with ORENCIA during pregnancy. Abatacept is an immunomodulatory agent.
It is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants [see Warnings and Precautions (5.4) ] . 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) ] .
🧒 Pediatric Use ▾
8.4Pediatric Use Polyarticular Juvenile Idiopathic Arthritis The safety and effectiveness of ORENCIA for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA) have been established (ORENCIA may be used as monotherapy or concomitantly with methotrexate). Use of ORENCIA for this indication is supported by evidence from the following studies: Intravenous Use : A randomized withdrawal efficacy, safety, and pharmacokinetic study of intravenous ORENCIA in 190 pediatric patients 6 to 17 years of age with pJIA [see Clinical Pharmacology (12.3) and Clinical Studies (14.2) ] .
Given that population pharmacokinetic (PK) analyses (after intravenous ORENCIA administration) showed that clearance of abatacept increased with baseline body weight, intravenous ORENCIA is administered either weight-based or weight ranged based [see Dosage and Administration (2.2) ] . Intravenous ORENCIA administration has not been studied in patients younger than 6 years of age. Subcutaneous Use : An open-label PK and safety study of subcutaneous ORENCIA in 205 pediatric patients aged 2 to 17 years old with pJIA, extrapolation of effectiveness of intravenous ORENCIA in patients with pJIA and subcutaneous ORENCIA in patients with RA [see Clinical Pharmacology (12.3) and Clinical Studies (14.2)] .
Given that population PK analyses (after subcutaneous ORENCIA injection) in pJIA patients showed that there was a trend toward higher clearance of abatacept with increasing body weight, subcutaneous ORENCIA dosage is weight range-based [see Dosage and Administration (2.2) ] . The safety and effectiveness of ORENCIA use in pJIA in pediatric patients less than two years of age have not been established. Acute Graft Versus Host Disease Prophylaxis The safety and effectiveness of ORENCIA for the prophylaxis of Acute Graft Versus Host Disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in pediatric patients aged 2 years of age and older undergoing HSCT from a matched or 1 allele-mismatched unrelated donor have been established.
Use of ORENCIA for this indication is supported by evidence from: • adequate and well-controlled studies in adults and pediatric patients aged 6 years and older administered a dose of 10 mg/kg intravenously on the day before transplantation followed by a dose of 10 mg/kg intravenously on Days 5, 14, and 28 after transplantation and • pharmacokinetic modeling and simulations of abatacept exposure in pediatric patients aged 2 to less than 6 years administered a dose of 15 mg/kg intravenously on the day before transplantation followed by a dose of 12 mg/kg intravenously on Days 5, 14, and 28 after transplantation.
Furthermore, the course of disease is sufficiently similar in pediatric patients aged 2 years to less than 6 years to that of patients aged 6 years and older to allow extrapolation of data to younger pediatric patients [see Clinical Pharmacology (12.3) and Clinical Studies (14.4) ] . No new safety signals were observed in pediatric patients aged 6 years and older in Study GVHD-1. The safety and effectiveness of ORENCIA for this indication have not been established in pediatric patients less than 2 years of age.
Psoriatic Arthritis Subcutaneous Administration The safety and effectiveness of subcutaneous ORENCIA have been established for treatment of psoriatic arthritis in pediatric patients 2 to 17 years old. Use of ORENCIA in this age group is supported by evidence from adequate and well-controlled studies of ORENCIA in adults with PsA, pharmacokinetic data from adult patients with RA, adult patients with PsA, and pediatric patients with pJIA, and safety data from clinical studies in pediatric patients 2 to 17 years old with pJIA using the subcutaneous formulation.
The observed pre-dose (trough) concentrations are generally comparable between adults with RA and PsA and pediatric patients with JIA with active polyarthritis,…
🧓 Geriatric Use ▾
8.5Geriatric Use Rheumatoid Arthritis 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 geriatric patients (patients aged 65 years of age and older) and younger adults, and other reported clinical experience has not identified differences in responses between geriatric patients and younger adults, but greater sensitivity of some geriatric patients cannot be ruled out.
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 geriatric population in general, caution should be used when treating geriatric patients. Acute Graft Versus Host Disease Prophylaxis Of the 116 patients in Study GVHD-1 who received ORENCIA at a dose of 10 mg/kg for the prophylaxis of aGVHD, 12 (10%) were 65 years of age and older, and 2 (2%) patients were 75 years of age and older [see Clinical Studies (14.4) ].
Clinical studies of ORENCIA for aGVHD did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.
🆘 Overdosage ▾
10 OVERDOSAGE ORENCIA doses up to 50 mg/kg (5 times the maximum recommended dose in patients aged 6 years and older and 3.3 times the maximum recommended dose in patients aged 2 to less than 6 years) have been administered intravenously without apparent toxic effect. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Abatacept, a selective costimulation modulator, inhibits T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of RA, pJIA and PsA and are found in the synovium of patients with RA, pJIA and PsA.
In vitro , abatacept decreases T-cell proliferation and inhibits the production of the cytokines TNF alpha (TNFα), interferon-γ, and interleukin-2. In a rat collagen-induced arthritis model, abatacept suppresses inflammation, decreases anti-collagen antibody production, and reduces antigen specific production of interferon-γ. The relationship of these biological response markers to the mechanisms by which ORENCIA exerts its clinical effects is unknown.
12.2Pharmacodynamics In clinical trials with ORENCIA at doses approximating 10 mg/kg, decreases were observed in serum levels of soluble interleukin-2 receptor (sIL-2R), interleukin-6 (IL-6), rheumatoid factor (RF), C-reactive protein (CRP), matrix metalloproteinase-3 (MMP3), and TNFα. The relationship of these biological response markers to the mechanisms by which ORENCIA exerts its clinical effects is unknown. No formal pharmacodynamic analyses of biologic response markers have been performed in patients exposed to ORENCIA as prophylaxis for aGVHD.
12.3Pharmacokinetics Healthy Adults and Adult RA - Intravenous Administration The pharmacokinetics of abatacept were studied in healthy adult subjects after a single 10 mg/kg intravenous infusion and in RA patients after multiple 10 mg/kg intravenous infusions of ORENCIA (see Table 7). Table 7: Pharmacokinetic Parameters (Mean, Range) in Healthy Subjects and RA Patients After 10 mg/kg ORENCIA Intravenous Infusion(s) PK Parameter Healthy Subjects (After 10 mg/kg Single Dose) n=13 RA Patients (After 10 mg/kg Multiple Doses a ) n=14 a Multiple intravenous infusions of ORENCIA were administered at days 1, 15, 30, and monthly thereafter.
Peak Concentration (C max ) [mcg/mL] 292 (175-427) 295 (171-398) Terminal half-life (t 1/2 ) [days] 16.7 (12-23) 13.1 (8-25) Systemic clearance (CL) [mL/h/kg] 0.23 (0.16-0.30) 0.22 (0.13-0.47) Volume of distribution (Vss) [L/kg] 0.09 (0.06-0.13) 0.07 (0.02-0.13) The pharmacokinetics of abatacept in RA patients and healthy subjects appeared to be comparable. In RA patients, after multiple intravenous infusions, the pharmacokinetics of abatacept showed proportional increases of C max and AUC over the dose range of 2 mg/kg to 10 mg/kg.
At 10 mg/kg, serum concentration appeared to reach a steady state by day 60 with a mean (range) trough concentration of 24 mcg/mL (1 to 66 mcg/mL). No systemic accumulation of abatacept occurred upon continued repeated treatment with 10 mg/kg at monthly intervals in RA patients. Population pharmacokinetic analyses in RA patients revealed that there was a trend toward higher clearance of abatacept with increasing body weight.
Age and gender (when corrected for body weight) did not affect clearance. Concomitant methotrexate, NSAIDs, corticosteroids, and TNF antagonists did not influence abatacept clearance. No formal studies were conducted to examine the effects of either renal or hepatic impairment on the pharmacokinetics of abatacept.
Adult RA - Subcutaneous Administration Abatacept exhibited linear pharmacokinetics following subcutaneous administration. The mean (range) for C min and C max at steady state observed after 85 days of treatment was 32.5 mcg/mL (6.6 to 113.8 mcg/mL) and 48.1 mcg/mL (9.8 to 132.4 mcg/mL), respectively. The bioavailability of abatacept following subcutaneous administration relative to intravenous administration was 79%.
Mean estimates for systemic clearance (0.28 mL/h/kg), volume of distribution (0.11 L/kg), and terminal half-life (14.3 days) were comparable between subcutaneous and intravenous administra…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Abatacept, a selective costimulation modulator, inhibits T-cell (T lymphocyte) activation by binding to CD80 and CD86, thereby blocking interaction with CD28. This interaction provides a costimulatory signal necessary for full activation of T lymphocytes. Activated T lymphocytes are implicated in the pathogenesis of RA, pJIA and PsA and are found in the synovium of patients with RA, pJIA and PsA.
In vitro , abatacept decreases T-cell proliferation and inhibits the production of the cytokines TNF alpha (TNFα), interferon-γ, and interleukin-2. In a rat collagen-induced arthritis model, abatacept suppresses inflammation, decreases anti-collagen antibody production, and reduces antigen specific production of interferon-γ. The relationship of these biological response markers to the mechanisms by which ORENCIA exerts its clinical effects is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING For Intravenous Infusion ORENCIA ® (abatacept) for injection is a white lyophilized powder for intravenous infusion after reconstitution and dilution. It is supplied as an individually packaged, single-dose vial (one may use less than the full contents of the vial or use more than one vial) with a silicone-free disposable syringe, providing 250 mg of abatacept: NDC 0003-2187-13: in a carton presentation For Subcutaneous Use ORENCIA ® (abatacept) injection and ORENCIA ® ClickJect (abatacept) injection are clear to slightly opalescent, colorless to pale yellow solutions for subcutaneous administration.
Prefilled Syringe ORENCIA (abatacept) injection, 50 mg/0.4 mL, 87.5 mg/0.7 mL, and 125 mg/mL, is supplied as single-dose disposable prefilled glass syringes with BD UltraSafe Passive™ needle guard and flange extenders. The Type I glass syringe has a coated stopper and fixed stainless steel needle (5 bevel, 29-gauge thin wall, ½-inch needle) covered with a rigid needle shield. The prefilled syringe provides ORENCIA in the following packages: NDC 0003-2814-11 (50 mg/0.4 mL): pack of 4 syringes with a passive needle safety guard NDC 0003-2818-11 (87.5 mg/0.7 mL): pack of 4 syringes with a passive needle safety guard NDC 0003-2188-11 (125 mg/mL): pack of 4 syringes with a passive needle safety guard ClickJect Autoinjector ORENCIA (abatacept) ClickJect, 125 mg/mL, is supplied as a single-dose disposable prefilled autoinjector.
The Type I glass syringe contained in the autoinjector has a coated stopper and fixed stainless steel needle (5 bevel, 27-gauge special thin wall, ½-inch needle) covered with a rigid needle shield. The autoinjector provides 125 mg of abatacept in 1 mL and is provided in the following package: NDC 0003-2188-51: pack of 4 autoinjectors Storage Refrigerate ORENCIA lyophilized powder supplied in a vial 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. Refrigerate ORENCIA solution supplied in a prefilled syringe or ClickJect autoinjector 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.
📦 Storage and Handling ▾
Storage Refrigerate ORENCIA lyophilized powder supplied in a vial 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.
Refrigerate ORENCIA solution supplied in a prefilled syringe or ClickJect autoinjector 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.
📋 Description ▾
11 DESCRIPTION Abatacept is a selective T-cell costimulation modulator. Abatacept is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression system.
The apparent molecular weight of abatacept is 92 kilodaltons. ORENCIA (abatacept) for injection is a sterile, white, preservative-free lyophilized powder for reconstitution and dilution prior to intravenous infusion. Following reconstitution of the lyophilized powder with 10 mL of Sterile Water for Injection, USP, the reconstituted solution of ORENCIA is clear, colorless to pale yellow, with a concentration of 25 mg/mL and with a pH range of 7.2 to 7.8.
Each single-dose vial of ORENCIA provides 250 mg abatacept, maltose (500 mg), monobasic sodium phosphate (17.2 mg), and sodium chloride (14.6 mg). ORENCIA (abatacept) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to pale-yellow solution with a pH range of 6.8 to 7.4 for subcutaneous administration. ORENCIA injection is supplied as a single-dose prefilled syringe or as a single-dose ClickJect autoinjector (see Table 6).
Table 6: Contents of ORENCIA Subcutaneous Injection Presentation Active Ingredient Quantity and Volume Inactive Ingredient Content ORENCIA injection 50 mg/0.4 mL prefilled syringe 50 mg of abatacept in 0.4 mL of solution dibasic sodium phosphate anhydrous (0.335 mg) monobasic sodium phosphate monohydrate (0.114 mg) poloxamer 188 (3.2 mg) sucrose (68 mg) qs to 0.4 mL Water for Injection, USP ORENCIA injection 87.5 mg/0.7 mL prefilled syringe 87.5 mg of abatacept in 0.7 mL of solution dibasic sodium phosphate anhydrous (0.587 mg) monobasic sodium phosphate monohydrate (0.200 mg) poloxamer 188 (5.6 mg) sucrose (119 mg) qs to 0.7 mL Water for Injection, USP ORENCIA injection 125 mg/mL prefilled syringe and ClickJect autoinjector 125 mg of abatacept in 1 mL of solution dibasic sodium phosphate anhydrous (0.838 mg) monobasic sodium phosphate monohydrate (0.286 mg) poloxamer 188 (8 mg) sucrose (170 mg) qs to 1 mL Water for Injection, USP Unlike the lyophilized formulation for intravenous use, the ORENCIA solutions for subcutaneous administration contain no maltose.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Increased Risk of Infection with Concomitant Use With Immunosuppressants for RA Inform patients that the concomitant use with other immunosuppressives (e.g., biologic DMARDs, JAK inhibitors) is not recommended [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ]. Hypersensitivity Reactions Instruct patients to immediately tell their healthcare professional if they experience symptoms of an allergic reaction on the day of administration or the day after ORENCIA administration [see Warnings and Precautions (5.2) ] .
Infections Inform patients that serious infections have been reported in patients receiving ORENCIA [see Warnings and Precautions (5.3) ] . Immunizations Inform patients that live vaccines should not be given concurrently with ORENCIA or within 3 months of its discontinuation [see Warnings and Precautions (5.4) ] . Blood Glucose Testing Maltose is contained in ORENCIA for intravenous administration and can give falsely elevated blood glucose readings with certain blood glucose monitors on the day of ORENCIA infusion.
Advise patients treated with intravenous ORENCIA who are using GDH-PQQ-based monitoring systems for glucose (e.g., diabetics) to consider using other methods for glucose monitoring. This recommendation is not applicable to patients treated with subcutaneous ORENCIA [see Drug Interactions (7.2) ] . Disposal of Prefilled Syringes and ClickJect Autoinjectors Advise patients to follow disposal instructions in the Instructions for Use.
A puncture-resistant container for disposal of needles and syringes should be used. Instruct patients that they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients not to recycle their used sharps disposal container.