Abataceptdosage

Intravenous Use for Adult RA and Adult PsA

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

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

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

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

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

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

Administer as a 30-minute intravenous infusion for RA, pJIA, and adult PsA.

Administer as a 60-minute intravenous infusion for aGVHD prophylaxis.

See the Full Prescribing Information for preparation and administration instructions for intravenous infusion and recommendations for subcutaneous use. Prepare ORENCIA using only the silicone-free disposable syringe.

2.1 Dosage 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 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. For patients switching from ORENCIA intravenous therapy to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose.

2.2 Dosage in

Polyarticular Juvenile Idiopathic Arthritis For pediatric patients with pJIA, either administer ORENCIA as an intravenous infusion (only patients 6 years of age and older) or as a subcutaneous injection (only patients 2 years of age and older). ORENCIA may be used as monotherapy or concomitantly with methotrexate. Intravenous Dosage Administer ORENCIA as a 30-minute intravenous infusion based on body weight:

For body weight less than 75 kg, administer a dose of 10 mg/kg.

For body weight of 75 kg or greater, administer as per the recommendations in Table 1 (follow the adult intravenous dosing regimen), not to exceed a maximum dose of 1,000 mg. Following the initial intravenous infusion, administer infusions at 2 and 4 weeks and every 4 weeks thereafter. Immediately discard any unused portion in the vials. Subcutaneous Dosage Administer ORENCIA for subcutaneous injection, without an intravenous loading dose, utilizing the weight range-based dosing as recommended in Table 2. Subsequently administer once weekly. Table 2: Dose of ORENCIA for Subcutaneous Administration in Patients 2 Years of Age and Older with pJIA Body Weight of Pediatric 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 Patients with pJIA may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determine it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

2.3 Dosage in

Psoriatic Arthritis Adult Patients For adult patients with psoriatic arthritis, administer as an intravenous infusion or a subcutaneous injection. ORENCIA may be used with or without non-biologic DMARDs. Intravenous Dosage Administer ORENCIA as a 30-minute intravenous infusion utilizing the weight range-based dosing specified in Table 1. Following the initial intravenous administration, administer an intravenous infusion at 2 and 4 weeks and every 4 weeks thereafter. Subcutaneous Dosage Administer 125 mg of ORENCIA subcutaneously once weekly (no intravenous loading dose is needed). For patients switching from ORENCIA intravenous infusions to subcutaneous administration, administer the first subcutaneous dose instead of the next scheduled intravenous dose. Pediatric Patients Administer ORENCIA as a subcutaneous injection in pediatric patients 2 years of age and older with psoriatic arthritis. ORENCIA may be used as monotherapy or concomitantly with methotrexate. Intravenous administration is not approved for pediatric patients with psoriatic arthritis. Subcutaneous Dosage Administer ORENCIA for subcutaneous injection weekly, utilizing the weight range-based dosage as recommended in Table 3.

Table 3: Dose of ORENCIA for Subcutaneous Administration in Patients 2 Years of Age and Older with Psoriatic Arthritis Body Weight of Pediatric 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 Pediatric patients with psoriatic arthritis may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determine it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested.

2.4 Dosage in

Prophylaxis of Acute Graft versus Host Disease in Adults and Pediatric Patients Aged 2 Years and Older Antiviral Prophylactic Treatment Before administering ORENCIA, administer recommended antiviral prophylactic treatment for Epstein-Barr Virus (EBV) reactivation, and continue for six months following HSCT. In addition, consider prophylactic antivirals for Cytomegalovirus (CMV) infection/reactivation during treatment and for six months following HSCT. Intravenous Dosing Regimen For patients 6 years and older, administer ORENCIA 10 mg/kg (maximum dose of 1,000 mg) as an intravenous infusion over 60 minutes on the day before transplantation (Day -1), followed by administration on Days 5, 14, and 28 after transplantation. For patients 2 to less than 6 years old, administer ORENCIA 15 mg/kg as an intravenous infusion over 60 minutes on the day before transplantation (Day -1), followed by 12 mg/kg as an intravenous infusion over 60 minutes on Days 5, 14, and 28 after transplantation.

2.5 Preparation and

Administration Instructions for Intravenous Infusion Calculate the ORENCIA dose, the total volume of reconstituted solution required, and the number of ORENCIA vials needed. For a full dose, less than the full contents of one vial or more than one vial may be needed. Using aseptic technique, reconstitute, dilute, and then administer ORENCIA as follows: Reconstitution 1) Use the vial only if the vacuum is present. 2) Reconstitute each vial of supplied ORENCIA lyophilized powder (each vial supplies 250 mg of abatacept) with 10 mL of Sterile Water for Injection, USP (direct the stream toward the inside wall of the vial) to obtain a concentration of 25 mg/mL. Use only the provided silicone-free syringe with an 18- to 21-gauge needle: a. If the ORENCIA lyophilized powder is accidently reconstituted using a siliconized syringe, the solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes). b. If the silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe. To obtain new silicone-free syringes, contact Bristol-Myers Squibb at 1-800-ORENCIA. 3) Gently swirl the vial to minimize foam formation, until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous agitation. 4) Upon complete dissolution of the lyophilized powder, vent the vial with a needle to dissipate any foam that may be present. 5) Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow). Do not use if opaque particles, discoloration, or other foreign particles are present. 6) Repeat steps 2) through 5) if two, three, or four vials are needed for a dose (see Table 1). Dilution 7) Must further dilute the reconstituted ORENCIA solution to 100 mL as follows: a. From a 100 mL infusion bag or bottle of 0.9% Sodium Chloride Injection, USP, withdraw a volume equal to the volume of the reconstituted ORENCIA solution required for the patient’s dose. b. Slowly add the reconstituted ORENCIA solution(s) into the infusion bag or bottle using the silicone-free disposable syringe provided with each vial. c. 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 abatacept added, but will be no more than 10 mg/mL. Immediately discard any unused portion in the ORENCIA vial. Administration 8) Prior to administration, visually inspect the ORENCIA diluted solution for particulate matter and discoloration. Discard the diluted solution if any particulate matter or discoloration is observed. 9) Using an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (pore size of 0.2 μm to 1.2 μm), administer the entire diluted ORENCIA solution over:

30 minutes for RA, pJIA, and adults with PsA

60 minutes for aGVHD prophylaxis 10) Must complete the infusion of the diluted ORENCIA solution within 24 hours of reconstitution of the ORENCIA vials. Do not infuse ORENCIA 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 drugs. Storage of Diluted ORENCIA Solution May store the diluted ORENCIA solution at room temperature or refrigerate at 2ºC to 8ºC (36ºF to 46ºF) up to 24 hours before use. Discard the diluted solution if not administered within 24 hours.

2.6 Recommendations for

Subcutaneous Administration ORENCIA prefilled syringes and ORENCIA ClickJect autoinjectors are intended for:

Subcutaneous use only and are not intended for intravenous infusion.

Use under the guidance of a healthcare practitioner. After proper training in subcutaneous injection technique, a patient or the patient’s caregiver may administer a subcutaneous injection of ORENCIA (ClickJect autoinjector or prefilled syringe) if a healthcare practitioner determines that it is appropriate. Instruct patients and/or caregivers to follow the directions provided in the Instructions for Use for additional details on administration. Specifically instruct them to inject the full amount (which provides the proper dose of ORENCIA), rotate injection sites, and to avoid injections into areas where the skin is tender, bruised, red, or hard. Visually inspect 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 to slightly opalescent and colorless to pale yellow.