Abatacept

Class and Category

Pharmacologic class: Selective costimulation modulator

Therapeutic class: Antiarthritic (psoriatic, rheumatic)

Indications and Dosages

To reduce signs and symptoms, induce a major clinical response, inhibit the progression of structural damage, and improve physical function in patients with moderate to severe active rheumatoid arthritis as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists; to treat active psoriatic arthritis

I.V. INFUSION

• Adults weighing more than 100 kg (220 lb). Initial: 1,000 mg infused over 30 min, repeated at 2 and 4 wk after the first infusion and every 4 wk thereafter.
• Adults weighing 60 to 100 kg (132 to 220 lb). Initial: 750 mg infused over 30 min, repeated at 2 and 4 wk after the first infusion and every 4 wk thereafter.
• Adults weighing less than 60 kg (132 lb). Initial: 500 mg infused over 30 min, repeated at 2 and 4 wk after the first infusion and every 4 wk thereafter.

SUBCUTANEOUS INJECTION

• Adults. Following a single I.V. loading dose as per body weight categories listed above for treatment of rheumatoid arthritis, 125 mg given within a day, followed by 125 mg once wk. 125 mg once wk for treatment of rheumatoid arthritis when I.V. loading dose is not used or to treat psoriatic arthritis.

DOSAGE ADJUSTMENT For patient transitioning from I.V. therapy to Subcutaneous (SubQ) injection, first SubQ dose should be administered instead of the next scheduled I.V. dose.

To reduce signs and symptoms of moderate to severe active polyarticular juvenile idiopathic arthritis as monotherapy or concomitantly with methotrexate

I.V. INFUSION

• Children ages 6 to 17 weighing more than 100 kg (220 lb). Initial: 1,000 mg infused over 30 min, repeated at 2 and 4 week (wk) after the first infusion and every 4 week thereafter.
• Children ages 6 to 17 weighing 75 to 100 kg (165 to 220 lb). Initial: 750 mg infused over 30 min, repeated at 2 and 4 wk after the first infusion and every 4 wk thereafter.
• Children ages 6 to 17 weighing less than 75 kg (165 lb). Initial: 10 mg/kg infused over 30 min, repeated at 2 and 4 wk after the first infusion and every 4 wk thereafter.

SUBCUTANEOUS INJECTION

• Children age 2 and over weighing 50 kg (110 lb) or more. 125 mg once wk.
• Children age 2 and over weighing 25 kg (55 lb) to less than 50 kg (110 lb). 87.5 mg once wk.
• Children age 2 and over weighing 10 kg (22 lb) to less than 25 kg (55 lb). 50 mg once wk.

Mechanism of Action

Inhibits T- cell activation by binding to CD80 and CD86 to block interaction with CD28. CD28 is part of the costimulatory signal needed for full activation of T cells. Activated T cells have been implicated in the pathogenesis of rheumatoid arthritis. With decreased proliferation of T cells, inflammation and other evidence of rheumatoid arthritis decrease.

Incompatibilities

Don’t infuse abatacept solution with other drugs in the same intravenous line concurrently because it is not known whether the drugs may interact.

Contraindications

Hypersensitivity to abatacept or its components

Interactions

DRUGS

live-virus vaccines: Possibly decreased response to vaccine, and risk of infection with live virus tumor necrosis factor antagonists: Increased risk of serious infection.

Adverse Reactions

CNS: Dizziness, fever, headache

CV: Hypertension, hypotension

EENT: Nasopharyngitis, rhinitis, sinusitis

GI: Abdominal pain, diarrhea, diverticulitis, dyspepsia, nausea

GU: Acute pyelonephritis, UTI

MS: Back or limb pain

RESP: Bronchitis, COPD worsening, cough, dyspnea, pneumonia, upper respiratory tract infection, wheezing

SKIN: Cellulitis, flushing, pruritus, rash, urticaria

Other: Anaphylaxis, antibody formation against abatacept, herpes simplex, herpes zoster infection, flu-like symptoms, malignancies, serious infections such as sepsis, varicella infection

Childbearing Considerations

PREGNANCY

It is not known if drug can cause fetal harm. Use with caution only if benefit to mother outweighs potential risk to fetus.

LACTATION

It is not known if drug is present in breast milk. Patient should check with prescriber before breastfeeding.

Nursing Considerations

• Screen patient for latent tuberculosis with a tuberculin skin test before starting abatacept. If test is positive, expect to provide treatment, as ordered, before starting abatacept. Also screen patient for hepatitis B. If present, expect abatacept to be withdrawn because antirheumatic therapies such as abatacept may reactivate hepatitis B.
• Review patient’s immunization record, and make sure all immunizations are current before therapy starts. Drug may blunt effectiveness of some vaccines and increase the risk of infection with live viruses.
• Use cautiously in patients with a history of recurrent infections, underlying conditions that may predispose them to infection, or existing chronic, latent, or localized infection. They have an increased risk of infection with abatacept therapy.
• Use cautiously in patients with COPD and monitor respiratory status closely because abatacept may worsen COPD and increase the risk of adverse respiratory reactions.
• Know that tumor necrosis factor antagonists shouldn’t be given with abatacept because of an increased risk of serious infection.
• Prepare for I.V. injection, by reconstituting each vial with 10 ml of sterile water for injection, directing the stream of sterile water to the glass wall of the vial to minimize foaming. Use only the silicone-free disposable syringe provided with each vial because a siliconized syringe may cause translucent particles to form in solution. Also use an 18- to 21-gauge needle. After injecting sterile water into vial, gently swirl vial until contents are completely dissolved. To minimize foaming, don’t shake. Vent the vial with a needle to dissipate any foam that may be present.

• Dilute further the reconstituted solution with 0.9% sodium chloride injection to achieve a final solution volume of 100 ml. Slowly add solution into infusion bag or bottle using the same siliconefree disposable syringe provided with each vial. Mix gently. Do not shake the bag or bottle.
• Give I.V. dose after dilution over 30 minutes using an infusion set and a sterile, nonpyrogenic, low protein-binding filter with a pore size of 0.2 μm.
• Be aware that once fully diluted, I.V. solution may be kept for 24 hours at room temperature or refrigerated. If reconstituted solution isn’t used within 24 hours, discard.
• Watch patient closely for infusion-related reactions that may occur within 1 hour of the start of the infusion. Adverse reactions to be alert for include dizziness, headache, and hypertension. Less commonly a patient may experience cough, dyspnea, flushing, hypersensitivity, hypotension, nausea, pruritus, rash, and wheezing. Notify prescriber if present, but know that most patients need not discontinue abatacept because of these events unless severe.
• Administer subcutaneous injection using only the supplied 125 mg/ml single-dose prefilled glass syringe or the prefilled ClickJect autoinjector. Know that the 125 mg/syringe or autoinjector are never to be used for intravenous infusion.
• Rotate sites and never give in areas where the skin is tender, bruised, red, or hard.
• Monitor patient closely for evidence of hypersensitivity reaction such as dyspnea, pruritus, rash, urticaria, or wheezing after administering abatacept. If present, notify prescriber, and provide emergency care, as ordered.
• Monitor patient closely for evidence of infection or malignancy because abatacept inhibits T-cell activation, increasing the risk of both.

PATIENT TEACHING

• Instruct patient receiving abatacept subcutaneously on how to administer the drug. Inform patient that injection sites should be rotated and should never be administered in an area where the skin is tender, bruised, red, or hard.
• Instruct patient self-administering abatacept subcutaneously to use a puncture-resistant container for disposal of needles and syringes. Have patient check with her community guidelines for correct way to dispose of a sharps container and stress the importance of not recycling the sharps container.
• Instruct patient not to receive immunizations with live vaccines during abatacept therapy and for 3 months afterward.
• Advise patient to tell prescriber of all medications being taken, including over-the-counter drugs and other biologic drugs.
• Emphasize need to report any evidence of infection or hypersensitivity to prescriber.
• Alert patient that abatacept may increase the risk of maligancy.
• Warn patient to avoid crowds and people with infections.
• Inform women to report known or suspected pregnancy. Encourage patient to register with the pregnancy exposure registry.