Abatacept (Orencia)

ABATACEPT (Orencia), 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 and are found in the synovium of patients with RA.

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 abatacept exerts its effects in RA is unknown. .

Online Resources from the Manufacturer

  1. Patient Medication Guide and Prescribing Information – Package Inserts
  2. Health Professionals can download the full Prescribing Information - Prescribing Information

Indications and Dosing

Abatacept is indicated for:

  1. Rheumatoid arthritis
  2. Polyarticular juvenile idiopathic arthritis in children 6 years of age or older

Intravenous Dosing:

  1. Following the initial dose of abatacept, readminister at 2 weeks and 4 weeks after the initial infusion, then every 4 weeks thereafter.
    Body Weight of Patient Dose Number of Orencia Vials
    (each vial = 250 mg Orencia)
    <60 kg
    60 to 100 kg
    >100 kg
    500 mg
    750 mg
    1000 mg
    2
    3
    4
  2. 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 abatacept following the adult dosing regimen, not to exceed a maximum dose of 1000 mg.

Subcutaneous Dosing

  1. 125 mg subcutaneously (SC) once weekly. Note: SC dosing may be initiated with or without an I.V. loading dose.
  2. If initiating with an I.V. loading dose, administer the initial I.V. infusion (using the weight-based dosing), then administer 125 mg subcutaneously within 24 hours of the infusion, followed by 125 mg subcutaneously once weekly thereafter.
  3. If transitioning from I.V. therapy to SC therapy, administer the first SC dose instead of the next scheduled I.V. dose.

Contraindications

  • None

Warnings and Precautions

  1. Hypersensitivity including anaphylactic reactions may occur. Discontinue treatment if anaphylaxis or other serious allergic reaction occurs.

Serious and potentially fatal infections have occurred with abatacept. The most common serious infections were pneumonia, cellulitis, urinary tract infection, bronchitis, diverticulitis, and acute pyelonephritis. Advise patients to seek prompt medical attention if they develop signs of symptoms of an infection.

  1. Live vaccines should not be given concurrently
  2. Caution if chronic or recurrent infections
  3. Caution if latent tuberculosis
  4. Caution if HPV infection
  5. Caution if COPD
  6. Caution if immunosuppressed
  7. Caution if malignancy history or risk
  8. Caution in elderly patients

Common Adverse Effects after Administration of Abatacept

  1. Headache
  2. Nausea
  3. Infections: Upper respiratory infections, sinusitis, bronchitis, urinary tract infections, cellulitis, and herpes zoster and simplex may occur. Serious infections, including pneumonia and sepsis, have been reported. These infections occur particularly in patients taking other immunosuppressive agents, such as prednisone or methotrexate, or if the patient has a history of past recurrent infections or medical conditions that predispose them to infections. Reactivation of hepatitis B may also occur with abatacept. Abatacept 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 abatacept, and do not require drug discontinuation.
  6. Children and adolescents may also have:
    • Diarrhea
    • Fever
    • Abdominal Pain

Rare Adverse Effects after Administration of Abatacept

  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 abatacept infusion due to the maltose contained in the intravenous formulation

Pre-Infusion Checklist

  1. Tuberculosis Screening
    • 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)
          • Consider chest x-ray in patients with TB risk factors but negative screening tests
          • 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)
    • Consider repeating screening tests if patient has had recent travel to TB endemic country or change in risk factors for TB exposure
  2. Negative Hepatitis B Screen
  3. Pediatric patients should be brought up-to-date with immunizations prior to starting abatacept. Live vaccines should not be given concurrently or within 3 months of discontinuation of abatacept.
  4. Ask patient if he/she

    (If the answer is yes to any of these questions, review with ordering)

    • Has had any current or recent bouts of illness or infection?
    • Is taking any antibiotics or other antimicrobial therapy?
    • Has had a recent vaccination?
    • Has any upcoming surgeries?
    • Has a history of chronic obstructive pulmonary disease (COPD)? Patients with COPD may have more respiratory adverse events, such as worsening of asthma.

Medication Preparation

Intravenous abatacept is provided as a lyophilized powder in preservative-free, single-use vials. Each abatacept vial provides 250 mg of abatacept for administration. After reconstitution, the concentration of abatacept in the vial is 25 mg/mL. If the abatacept 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. Remove the flip-top of the vial and swab with alcohol before needle puncture.
  2. The abatacept 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.
  3. To reconstitute the abatacept 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 abatacept solution must be further diluted to 100 mL in one of 2 ways, 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 abatacept solution required for the patient's dose. Slowly add the reconstituted abatacept 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 abatacept 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 abatacept 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. Abatacept 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 abatacept with other agents.
  9. Infusion of the fully diluted abatacept solution must be completed within 24 hours of reconstitution of the abatacept vials. The fully diluted abatacept 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.

Medication Administration and Monitoring

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 abatacept is advised.
  3. Total infusion time is 30 minutes, plus 5-10 minutes for the flush.

Vital Signs Monitoring Obtain vital signs (patient temperature, blood pressure and pulse) upon arrival prior to infusion, after the start of the infusion, upon discontinuing infusion, and before the patient departs the facility. 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 abatacept given by the patient at home.

Review Orders and Obtain IV Access

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

  1. 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 abatacept 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.
  2. Check for pre-medication orders. Give oral acetaminophen (Tylenol) and/or diphenhydramine (Benadryl) or IV Push 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.

Subcutaneous administration: Allow prefilled syringe to warm to room temperature (for 30-60 minutes) prior to administration. Inject into the front of the thigh (preferred), abdomen (except for 2-inch area around the navel), or the outer area of the upper arms (if administered by a caregiver). Rotate injection sites (≥1 inch apart); do not administer into tender, bruised, red, or hard skin.

Managing 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 abatacept. If a patient reports mild reactions (such as dizziness, hives, flushing, chills, etc.), slow down the infusion rate and assess the 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. 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.

Additional Considerations:

Updated January 2017 - 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.

© 2017 American College of Rheumatology