Orencia

abatacept

Orencia

Pharmacologic class: Selective costimulation modulator

Therapeutic class: Antirheumatic

Pregnancy risk category C

Action

Inhibits T-cell activation by binding to CD80 and CD86, blocking interaction with CD28. (This interaction triggers costimulatory signal necessary for full activation of T cells, which are implicated in rheumatoid arthritis pathogenesis.)

Availability

Injection: 125 mg/ml in prefilled syringes

Powder for infusion (lyophilized): 250 mg/15 ml in single-use vial

Indications and dosages

➣ Moderate to severe adult rheumatoid arthritis as monotherapy or concomitantly with disease-modifying antirheumatic drugs other than tumor necrosis factor (TNF) antagonists

Adults weighing less than 60 kg (132 lb): 500 mg I.V. given over 30 minutes at weeks 0, 2, and 4; thereafter, give every 4 weeks. Or, 500 mg I.V. as a loading dose followed by 125 mg subcutaneously within a day, followed by 125 mg subcutaneously once weekly. For patients unable to receive an infusion, initiate weekly injections subcutaneously without an I.V. loading dose.

Adults weighing 60 to 100 kg (132 to 220 lb): 750 mg I.V. given over 30 minutes at weeks 0, 2, and 4; thereafter, give every 4 weeks. Or 750 mg I.V. as a loading dose followed by 125 mg subcutaneously within a day, followed by 125 mg subcutaneously once weekly. For patients unable to receive an infusion, may initiate weekly injections subcutaneously without an I.V. loading dose.

Adults weighing more than 100 kg:

1 g I.V. given over 30 minutes at weeks 0, 2, and 4; thereafter, give every 4 weeks. Or 1 g I.V. as a loading dose followed by 125 mg subcutaneously within a day, followed by 125 mg subcutaneously once weekly. For patients unable to receive an infusion, may initiate weekly injections subcutaneously without an I.V. loading dose.

➣ Moderately to severely active polyarticular juvenile idiopathic arthritis as monotherapy or concomitantly with methotrexate

Children age 6 and older weighing less than 75 kg: 10 mg/kg I.V. at weeks 0, 2, and 4; thereafter give every 4 weeks. Not to exceed a maximum dosage of 1 g.

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• increased risk of infection or history of recurrent infections, immunocompromised state, chronic obstructive pulmonary disease (COPD)

• concurrent use of concomitant TNF antagonists

• patients older than age 65

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

See Reconstitute each vial with 10 ml sterile water for injection, using only silicone-free disposable syringe included with product.

See During reconstitution, rotate vial by swirling gently. Avoid prolonged or vigorous agitation. Don't shake.

• Further dilute reconstituted solution to volume of 100 ml with normal saline solution.

• Use silicone-free syringe to add drug to infusion bag or bottle, and mix gently. Resulting drug concentration should be 5 mg/ml for two vials, 7.5 mg/ml for three vials, or 10 mg/ml for four vials, respectively.

• Administer infusion over 30 minutes using infusion set and nonpyrogenic, low protein-binding filter.

• Complete infusion within 24 hours of vial reconstitution.

• Don't infuse other drugs concurrently through same I.V. line.

• Watch for infusion-related reactions (hypotension or hypertension, dyspnea, nausea, dizziness, headache, flushing, urticaria, pruritus, rash, cough, or wheezing), which usually occur within 1 hour of administration. Be prepared to intervene appropriately.

Adverse reactions

CNS: headache, dizziness

CV: hypertension, hypotension

EENT: nasopharyngitis

GI: nausea, dyspepsia, diverticulitis

GU: urinary tract infection, acute pyelonephritis

Musculoskeletal: back pain, extremity pain

Respiratory: cough, upper respiratory tract infection, pneumonia, wheezing, bronchitis, dyspnea

Skin: rash, flushing, urticaria, pruritus

Other: herpes zoster, pain, injection-site reactions, malignancies, infusion-related reactions, hypersensitivity reaction

Interactions

Drug-drug. Immunizations: possible decrease in immunization efficacy

Patient monitoring

• Continue to monitor patient for infusion-related events.

• Assess patient's overall health at each visit to evaluate infection status.

• Closely monitor COPD patient because of increased likelihood of adverse events.

Patient teaching

• If patient will self-administer drug, tell him to follow exact directions for injection and proper disposal of needles and syringes.

• Instruct patient to report signs and symptoms of infection.

• Caution patient to avoid immunizations during or within 3 months of stopping drug.

• Tell female with childbearing potential that pregnancy and breastfeeding aren't recommended during therapy.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs mentioned above.

abatacept

(a-bat-a-cept) abatacept,

Orencia

(trade name)

Classification

Therapeutic: antirheumatics
Pharmacologic: fusion proteins
Pregnancy Category: C

Indications

Reduction of signs/symptoms and disease progression in moderate to severely active rheumatoid arthritis in adults (to be used as monotherapy or in with other disease modifying antirheumatic drugs (DMARDS), other than tumor-necrosis factor (TNF) inhibitors.Reduction of signs/symptoms in children (≥6 yr) with moderate to severely active polyarticular juvenile idiopathic arthritis (to be used as monotherapy or with methotrexate).

Action

Inhibits T cell activation (and the inflammatory process) by binding to specific receptors.

Therapeutic effects

Decreased progression of rheumatoid arthritis.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Unknown.Metabolism and Excretion: Unknown.Half-life: 13 days.

Time/action profile (improvement in symptoms)

ROUTEONSETPEAKDURATION
IVwithin 15 days–3 mo6–12 mo3 yr (maintenance of response)

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent use of tumor necrosis factor (TNF) antagonists or anakinra; Lactation: Discontinue drug or provide formula.Use Cautiously in: Patients with chronic obstructive pulmonary disease (↑ risk of exacerbations and other adverse events); Geriatric: ↑ risk of adverse reactions; Pediatric: Children <6 yr (safety not established); Obstetric: Use only if clearly needed.

Adverse Reactions/Side Effects

Central nervous system

  • headache (most frequent)
  • dizziness

Miscellaneous

  • hypersensitivity reactions including anaphylaxis (life-threatening)
  • infections
  • infusion-related events

Interactions

Drug-Drug interaction

Concurrent use with tumor necrosis factor (TNF) antagonists may ↑ risk and severity of infections.May ↑ incidence and risk of adverse reactions from live-virus vaccines.

Route/Dosage

Rheumatoid Arthritis

Intravenous (Adults) <60 kg—500 mg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter; 60–100 kg—750 mg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter; >100 kg—1000 mg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter.Subcutaneous (Adults) Patient should receive single IV dose (according to weight-based dosing guidelines above), then give 125 mg subcut within 1 day, then give 125 mg subcut once weekly; if patient cannot receive IV dose, initiate once weekly subcut injections; if transitioning from IV therapy, administer next scheduled dose as subcut injection.

Juvenile Idiopathic Arthritis

Intravenous (Children 6–17 yr and ≥75 kg) 75–100 kg—750 mg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter; >100 kg—1000 mg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter.Intravenous (Children 6–17 yr and <75 kg) 10 mg/kg initially; repeat dose at 2 wk and 4 wk after initial dose, then q 4 wk thereafter.

Availability

Lyophilized powder for IV administration: 250 mg/vial Solution for subcut administration (prefilled syringes): 125 mg/syringe

Nursing implications

Nursing assessment

  • Assess range of motion, degree of swelling, and pain in affected joints before and periodically during therapy.
  • Assess for infusion-related reaction (dizziness, headache, hypertension) and signs of allergic reaction (hypotension, urticaria, dyspnea). Infusion-related reactions usually occur within 1 hr of start of infusion. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of an anaphylactic reaction.
  • Assess for latent tuberculosis with a tuberculin skin test. If positive, tuberculosis should be treated prior to abatacept therapy.
  • Assess health status at each session. Monitor patients who develop a new infection while taking abatacept closely. Discontinue therapy in patients who develop a serious infection or sepsis. Do not initiate therapy in patients with active infections.
  • Lab Test Considerations: Pre-screen patient for viral hepatitis prior to therapy; may reactivate hepatitis. If test is positive, do not start abatacept.
    • Patients receiving IV abatacept may record false positive blood glucose due to maltose in injection; discuss with health care professional.

Potential Nursing Diagnoses

Impaired physical mobility (Indications)
Acute pain (Indications)

Implementation

  • Do not confuse Orencia with Oracea.
  • Subcutaneous: Remove prefilled syringe from refrigerator and allow to reach room temperature for 30–60 min; do not use other methods to warm solution. Leave needle cover on during warming. Inspect solution; do not administer solutions that are discolored, contain particulate matter; are expired, or do not have the correct amount of fluid in syringe. Front of thigh is the preferred site; abdomen except for 2 inches from navel or upper arm if administered by caregiver, may also be used. Pinch skin and inject at a 45° angle. Do not rub injection site. Rotate each injection at least 1 inch from last injection, avoid areas where skin is tender, bruised, red, or hard, or contains scars or stretch marks.
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute each vial with 10 mL of Sterile Water for Injection, using ONLY the SILICONE-FREE DISPOSABLE SYRINGE PROVIDED WITH EACH VIAL and an 18–21 gauge needle for a concentration of 25 mg/mL. Discard solutions prepared using siliconized syringes. Additional silicone-free syringes are available from manufacturer. Direct stream of sterile water to side of vial. Rotate vial by gently swirling to minimize foaming. Do no shake. Upon dissolution, vent vial to dissipate foam. Solution should be clear and colorless to pale yellow. Do not use solutions that are discolored or contain particulate matter. Diluent: Further dilute solution to 100 mL of 0.9% NaCl by withdrawing volume of abatacept solution from 100 mL infusion bag or bottle. Slowly add reconstituted solution using the same SILICONE-FREE DISPOSABLE SYRINGE PROVIDED WITH EACH VIAL. Mix gently. Concentration: Concentration will be 5, 7.5, or 10 mg/mL depending on whether 2, 3, or 4 vials were used. Discard unused portion of vial. Infusion must be completed within 24 hr of reconstitution. Diluted solution may be stored at room temperature or refrigerated before use.
  • Rate: Administer over 30 min with a sterile non-pyrogenic, low-protein-binding filter with a 0.2–1.2 micron pore size.
  • Y-Site Incompatibility: Do not infuse in same infusion line as other agents.

Patient/Family Teaching

  • Instruct patient on purpose of abatacept. Advise patient to read the Orencia Patient Information leaflet prior to each session. Provide an opportunity for patient to ask questions. If a dose is missed, ask health care professional when to schedule next dose.
  • Advise patient not to receive live vaccines during or 3 mo following therapy. Parents should be advised that children should complete immunizations to date before initiation of abatacept.
  • Advise patient that methotrexate, analgesics, NSAIDs, corticosteroids, and salicylates may be continued during therapy.
  • Instruct patient that abatacept should not be taken with TNF antagonists may increase risk for infections.
  • Instruct patient to notify health care professional if upper respiratory or other infections occur. Therapy may need to be discontinued if serious infection occurs.
  • Advise patient to notify health care professional if pregnancy is planned or suspected. Caution patient to avoid breastfeeding during therapy.

Evaluation/Desired Outcomes

  • Reduction in symptoms of rheumatoid arthritis.