Orencia

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 Adult Rheumatoid Arthritis

  ORENCIA^®is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).
• •the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).
  1.2 Polyarticular 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).
• •the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
  1.3 Psoriatic Arthritis

  ORENCIA is indicated for the treatment of patients 2 years of age and older with active psoriatic arthritis (PsA).
• •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 Prophylaxis 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.

Concomitant use of ORENCIA with other immunosuppressives [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended. (

• •Administer at 0, 2, and 4 weeks, and every 4 weeks thereafter, as a 30-minute infusion

• •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.

• •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.

• •Administer subcutaneously without an intravenous loading dose

• •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.

• •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.

• •Administer as a 30-minute intravenous infusion for RA, pJIA, and adult PsA.
  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.
• •Administer as a 60-minute intravenous infusion for aGVHD prophylaxis.
  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.
• •See the Full Prescribing Information for preparation and administration instructions for intravenous infusion and recommendations for subcutaneous use.
  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.
  Prepare ORENCIA using only the silicone-free disposable syringe.
  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.

• •
  Intravenous Infusion
•  For injection: 250 mg white lyophilized powder in a single-dose vial
  [see

  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

  [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 Vialsa
  aEach 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 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)

  [see Use in Specific Populations (8.4)]

  . ORENCIA may be used as monotherapy or concomitantly with methotrexate.

  Intravenous Dosage

  Administer ORENCIA as a 30-minute intravenous infusion based on body weight

  [see Dosage and Administration (2.5)]

  :

  • •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

  [see Dosage and Administration (2.6)]

  . 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)

  [see Dosage and Administration (2.6)]

  .

  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

  [see Use in Specific Populations (8.4)]

  . 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

  [see Dosage and Administration (2.6)]

  .

  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.

  ,

  2.5 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.

  )]
  .
• •
  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.

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

• •Concomitant use with a TNF antagonist can increase the risk of infections and serious infections.
  5.1 Increased 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.
• •Hypersensitivity and anaphylaxis have occurred.
  5.2 Hypersensitivity 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.
• •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 Infections

  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, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •Screen for latent TB infection prior to initiating therapy. Patients testing positive should be treated prior to initiating ORENCIA.
  5.3 Infections

  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, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •Screen for viral hepatitis prior to initiating ORENCIA.
  5.3 Infections

  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, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment with ORENCIA should be monitored closely. Administration of ORENCIA should be discontinued if a patient develops a serious infection.

  Prior to initiating ORENCIA, patients should be screened for latent tuberculosis (TB) infection according to current TB guidelines. ORENCIA has not been studied in patients with a positive TB screen, and the safety of ORENCIA in individuals with latent TB infection is unknown. Patients testing positive in TB screening should be treated by standard medical practice prior to therapy with ORENCIA.

  Antirheumatic therapies have been associated with hepatitis B reactivation. Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with ORENCIA. In clinical studies with ORENCIA, patients who screened positive for hepatitis were excluded from study.
• •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 Immunizations

  Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. ORENCIA-treated patients may receive current non-live vaccines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving ORENCIA. In addition, there are clinical considerations for administering live vaccines to infants who were exposed to ORENCIA while

  in utero [see Use in Specific Populations (8.1)]

  . Based on its mechanism of action, ORENCIA may blunt the effectiveness of some immunizations.
• •COPD patients may develop more frequent respiratory adverse reactions.
  5.5 Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD)

  In Study V, adult COPD patients treated with ORENCIA for RA developed adverse reactions more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to patients treated with placebo (27% vs 6%)

  [see Clinical Studies (14.1)and Adverse Reactions (6.1)]

  . Use of ORENCIA in patients with COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status.
• •Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) reactivation in patients treated for aGVHD prophylaxis.
  5.7 Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT)

  Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. Three of the four patients were EBV serology positive at baseline; one patient had negative baseline EBV serology with donor EBV serology unknown. Three of the 4 patients discontinued acyclovir prophylaxis at day 30 post-transplant. The range of time to onset of the events was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Provide prophylaxis for EBV infection for 6 months post-transplantation to prevent EBV-associated PTLD

  [see Dosage and Administration (2.4)]

  .

  Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% experienced CMV invasive diseases up to day 225 post-transplant. All the patients who experienced CMV invasive disease were CMV serology positive at baseline. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract

  [see Adverse Reactions (6.1)]

  .

  Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation

  [see Dosage and Administration (2.4)]

  .