Abatacept is a biologic response modifier that binds to CD80 and CD86 receptors on the antigen-presenting cell and prevents these receptors from binding to CD28 receptors on T cells, which decrease inflammation by downregulating T cell activation.

ORENCIA (abatacept)

Abatacept(Orencia) is a biologic response modifier that binds to CD80 and CD86 receptors on the antigen-presenting cell and prevents these receptors from binding to CD28 receptors on T cells, which decrease inflammation by downregulating T cell activation.

Orencia is supplied as a sterile, white, preservative-free, lyophilized powder for intravenous administration in 250mg single-use vials. Orencia should be protected from light and stored in the refrigerator (2⁰-6⁰C) until time of use. Following reconstitution with 10 ml of Sterile Water for Injection, USP, the solution of Orencia is clear, colorless to pale yellow, with a pH range of 7.2 to 7.8. Each single-use vial of Orencia provides 250 mg abatacept, 500 mg maltose, 17.2 mg monobasic sodium phosphate, and 14.6 mg sodium chloride for administration.  Orencia is also available in 125mg/mL pre-filled glass syringes for subcutaneous administration. Orencia pre-filled syringes should be protected from light and stored in the refrigerator (2⁰-6⁰C) until time of use.

Online Resource from Manufacturer

• Patient Medication Guide and Prescribing Information - http://packageinserts.bms.com/ppi/ppi_orencia.pdf  
• Health Professionals can download the full Prescribing Information- http://packageinserts.bms.com/pi/pi_orencia.pdf

Intravenous and Subcutaneous Injection Pre-Infusion Checklist

1. Tuberculosis Screening
2. Verify latent tuberculosis infection screening has been performed
   • Detailed history of patient tuberculosis exposure risk factors
   • Confirm the following:
   • Negative tuberculin skin test/PPD (<5mm induration) and/or Negative Interferon Gamma Release Assay (Quantiferon or T.Spot.TB test)
    
3. Consider chest x-ray in patients with TB risk factors but negative screening tests

-OR-

• Positive tuberculin skin test/PPD or positive Quantiferon/T.Spot.TB test with negative chest x-ray
  • Consider infectious disease consult and/or treating with isoniazid if tuberculosis history risk factors are present (TB may be in other tissue and may have negative chest x-ray)
   

-OR-

• Patient is at least 4 weeks post initiation of INH or other TB therapy
  • Consider repeating screening tests if patient has had recent travel to TB endemic country or change in risk factors for TB exposure
   

1. • Negative hepatitis B screen
   • Pediatric patients should be brought up-to-date with immunizations prior to starting Orencia. Live vaccines should not be given concurrently or within 3 months of discontinuation of Orencia.
    
2. Ask patient if he/she:

If the answer is yes to any of these questions, review with ordering provider.

Vital Signs Monitoring

Prior to intravenous infusion of Orencia, obtain vital signs (patient temperature, blood pressure and pulse) upon arrival, after the start of Orencia, upon discontinuing infusion, and before the patient departs the facility. However, if the patient has a prior history of an acute infusion reaction, monitor vitals every 10 minutes for 30 minutes and for 30 minutes after infusion. There is no need for vital signs to be done prior to subcutaneous injection of Orencia given by the patient at home.

Review Orders and Obtain IV Access

1. FDA-Approved Indications - Rheumatoid Arthritis & Polyarticular Juvenile Idiopathic Arthritis  in children 6 years of age or older
2.  For Abatacept Subcutaneous Dosing and Preparation (click link to subcutaneous abatacept section below)

- Abatacept Intravenous Dosing -

• Pediatric patients weighing less than 75 kg or more should receive 10 mg/kg based on the patient's body weight. Pediatric patients weighing 75 kg or more should be administered Orencia following the adult dosing regimen, not to exceed a maximum dose of 1000 mg.
• Prime tubing (20 drops/mL) with normal saline (NS) using a low-protein binding 0.2μm-1.2μm filter (alternatively, the filter may be placed on the Orencia IV tubing, if it is Y-sited into the normal saline line. Start IV using aseptic technique and begin infusing with 100mL NS bag; set rate to keep open.
• Check for pre-medication orders. Give oral acetaminophen (Tylenol) and/or diphenhydramine (Benadryl) or IVPush pre-medications (such as IV diphenhydramine and/or methylprednisolone) if ordered.  If a patient is driving home after the infusion, non-sedating antihistamines such as cetirizine (Zyrtec) or fexofenadine (Allegra) may be used in place of diphenhydramine.

***Do not reconstitute Orencia vials until after obtaining intravenous access***

Intravenous Orencia Drug Reconstitution and Preparation

Intravenous Orencia is provided as a lyophilized powder in preservative-free, single-use vials. Each Orencia vial provides 250 mg of abatacept for administration. After reconstitution, the concentration of abatacept in the vial will be 25 mg/mL. If the Orencia powder is accidentally reconstituted using a silicon syringe, the solution may develop a few translucent particles. Discard any solutions prepared using silicon syringes.

For information on obtaining additional SILICONE-FREE DISPOSABLE SYRINGES, contact Bristol-Myers Squibb 1-800-ORENCIA.

1. Use aseptic technique throughout. Remove the flip-top of the vial and swab with alcohol before needle puncture.
2. The Orencia powder in each vial must be reconstituted with 10 mL of Sterile Water for Injection, USP, using ONLY the SILICONE-FREE DISPOSABLE SYRINGE provided with each vial and an 18- to 21-gauge needle. If syringe is dropped or becomes contaminated use a new one. Contact Bristol-Myers Squibb on how to obtain new syringes. (1-877-O SOURCE)
3. To reconstitute the Orencia powder, direct the stream of Sterile Water for Injection, USP, against the glass wall of the vial. Do not use the vial if the vacuum is not present. Rotate the vial with gentle swirling until the contents are completely dissolved. Avoid prolonged or vigorous agitation. DO NOT SHAKE.
4. Upon complete dissolution of the lyophilized powder, the vial should be vented with a needle to dissipate any foam that may be present. After reconstitution, each milliliter will contain 25 mg (250 mg/10 mL).
5. The reconstituted Orencia solution must be further diluted to 100 mL as follows.

• From a 100 mL infusion bag or bottle, withdraw a volume of 0.9% Sodium Chloride Injection, USP, equal to the volume of the reconstituted Orencia solution required for the patient's dose (20ml if 2 vials, 30ml if 3 vials, 40ml if 4 vials). Slowly add the reconstituted Orencia solution into the infusion bag or bottle using the same SILICONE-FREE DISPOSABLE SYRINGE PROVIDED WITH EACH VIAL. Gently mix the solution. DO NOT SHAKE THE BAG OR BOTTLE. The final concentration of abatacept in the bag or bottle will depend upon the amount of drug added, but will be no more than 10 mg/mL. Any unused portions in the vials must be immediately discarded.

6. Prior to administration, the Orencia solution should be inspected visually for particulate matter and discoloration. Discard the solution if any particulate matter or discoloration is noted.
7. The entire, fully diluted Orencia solution should be administered over a period of 30 minutes and must be administered with an infusion set and a STERILE, NONPYROGENIC, LOW-PROTEIN-BINDING FILTER (pore size 0.2 μm to 1.2 μm).
8. Orencia should not be infused concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of Orencia with other agents.
9. Infusion of the fully diluted Orencia solution must be completed within 24 hours of reconstitution of the Orencia vials. The fully diluted Orencia solution may be stored at room temperature or refrigerated at 2ºC to 8ºC (36ºF to 46ºF) before use.
10. Discard the fully diluted solution if it is not administered within 24 hours.

Standard Infusion Checklist:

1. Infuse at 200mL/hour for 30 minutes
2. Completely infuse the entire volume. Utilizing a flush infusion through the infusion line to ensure complete infusion of Orencia is advised.
3. Total infusion time is 30 minutes, plus 5-10 minutes for the flush.

Abatacept Subcutaneous Injection Dosing

Subcutaneous Orencia 125mg prefilled syringes are ready-to-use without further preparation. Orencia syringes should be clear and colorless to pale-yellow. The entire syringe contents should be injected subcutaneously. Patients should be instructed to rotate injection sites. Appropriate sites include the thighs, outer upper arm, or the abdomen (avoid 2 inches around the navel or surgery scars). Detailed injection instructions are available for patientsin the Patient Medication Guide and Prescribing Information - http://packageinserts.bms.com/ppi/ppi_orencia.pdf

• Following a single intravenous loading dose of Orencia (dosed per body weight), the first Orencia 125mg subcutaneous injection should be administered within one day, followed by once weekly subcutaneous Orencia 125mg injection at home or physician's office
• Patients unable to receive the intravenous loading dose of Orencia may start weekly Orencia 125mg subcutaneous injections without an intravenous loading dose.
• Patients who have been managed with every 4-week intravenous Orencia infusions may be transitioned to subcutaneous Orencia injections by starting Orencia 125mg subcutaneous injections at the time that the next intravenous dose of Orencia is due instead of the IV dose, followed by weekly subcutaneous injections.

Managing Acute Infusion Reactions:

Acute infusion reaction can occur during the administration of this agent or within 1 hour after the infusion. Patients may also have an infusion reaction the following day after the infusion. Anaphylactoid and anaphylaxis reactions can result from Orencia. If patient reports mild reactions (such as dizziness, hives, flushing, chills, etc.), slow down the infusion rate and assess patient. For more severe reactions (such as difficulty breathing, chest pain, high or low blood pressure, swelling of face and hands, fever, chills or anaphylaxis) or where mild reactions persist, stop the infusion and treat the acute reaction. Then notify the supervising provider immediately to coordinate next plan of action. Patients should be informed that infusion reactions can be delayed, and should contact their physician at the first sign of an allergic reaction.

Adverse Effects after Administration of Orencia

1. Headache, dizziness
2. Nausea
3. Infections: Upper respiratory infections, nasopharyngitis, sinusitis, bronchitis, urinary tract infections, cellulitis, and herpes zoster and simplex may occur. Serious infections, including pneumonia and sepsis, have been reported, particularly if the patient is also taking other immunosuppressive agents, such as prednisone or methotrexate or has a history of past recurrent infections or medical conditions that predispose the patient to infections. Reactivation of hepatitis B may also occur with Orencia. Orencia should be suspended until the infection has resolved.
4. Patients with COPD have more respiratory adverse effects, such as cough, trouble breathing, or COPD exacerbation.
5. Injection site reactions can occur with subcutaneous Orencia, and do not require drug discontinuation.
6. Children and adolescents may also have:
   Diarrhea
   Fever
   Abdominal Pain

Rare Adverse Effects after Administration of Orencia

1. Antibodies against the abatacept molecule
2. Vasculitis
3. Some glucose monitoring test strips may have falsely elevated blood glucose test results on the day of Orencia infusion due to the maltose contained in the intravenous formulation of Orencia

Updated June 2013 - ARHP Practice Committee

Disclaimer:
The information contained in this biologic reference guide is offered solely for purposes of providing health care professionals with a quick and initial reference.  Before prescribing or administering any drug contained in this biologic reference guide, health professionals should read the manufacturer's complete prescribing information in order to be informed of the various clinical considerations to be taken into account.

The American College of Rheumatology is providing this information as a benefit and service in furtherance of its educational mission.  By providing this information, ACR is not endorsing or recommending any of the listed companies or any of their drugs or other products.  The information contained in the biologic reference guides reflect the conclusions of the individual companies and not those of the ACR which specifically disclaims any responsibility or liability for the use of such information and/or for the performance of any of the drugs listed in this biologic reference guide.