abatacept (Rx)

>10%

Headache (18%)

Nasopharyngitis (12%)

Nausea (>10%)

Infection (54% for adults & 36% for children)

1-10%

Dizziness (9%)

Cough (8%)

Back pain (7%)

Hypertension (7%)

Dyspepsia (6%)

Urinary Tract Infection (6%)

Rash (4%)

Pain in extremety (3%)

< 1%

Acute lymphocytic leukemia

Anaphylaxis

Cellulitis

COPD exacerbation

Disease flare

Diverticulitis

Dyspnea

Flushing

Hypersensitivity

Hypotension

Joint wear

Lung cancer

Lymphoma

Malignancies

Ovarian cyst

Pruitus

Pyelonephritis

Rhonchi

Urticaria

Varicella infection

Wheezing

Frequency Not Defined

Nausea

Abdominal pain

Diarrhea

Postmarketing Reports

New or worsening psoriasis

Contraindications

None listed by the manufacturer

Cautions

Appropriate medical support measures for treatment of hypersensitivity reactions should be available for immediate use in event of reaction; if an anaphylactic or other serious allergic reaction occurs, stop administration immediately; institute appropriate therapy; permanently discontinue therapy

Higher risk for serious infections; concomitant use with a TNF antagonist can also increase risk of infections and serious infections; concurrent therapy with another TNF antagonist not recommended; discontinue if serious infections develop

Serious infections, including sepsis and pneumonia, reported; 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

Healthcare providers should exercise caution when considering therapy 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 should be monitored closely; administration should be discontinued if a patient develops a serious infection

Antirheumatic therapies have been associated with hepatitis B reactivation; screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy

Prior to initiating therapy, patients should be screened for latent tuberculosis (TB) infection with a tuberculin skin test; therapy has not been studied in patients with a positive TB screen; safety of therapy in individuals with latent TB infection is unknown; patients testing positive in TB screening should be treated by standard medical practice prior to therapy

Prior to initiating therapy, update vaccinations in accordance with current vaccination guidelines; treated patients may receive current non-live vaccines; live vaccines should not be given concurrently or within 3 months after discontinuation; no data are available on secondary transmission of infection from persons receiving live vaccines to patients receiving therapy; based on mechanism of action, therapy may blunt effectiveness of some immunizations

Increased risk of lymphoma and lung cancer reported; significance unknown; increased risk of lymphoma associated with rheumatoid arthritis

Patients receiving therapy for RA reported to develop adverse events more frequently, including COPD exacerbations, cough, rhonchi, and dyspnea; therapy in patients with COPD should be undertaken with caution and such patients should be monitored for worsening of their respiratory status

The possibility exists for drugs inhibiting T cell activation, to affect host defenses against infections and malignancies since T cells mediate cellular immune responses; there have been reports of malignancies, including skin cancer in patients receiving therapy; periodic skin examinations are recommended for all treated patients, particularly those with risk factors for skin cancer

Higher incidence of infections and malignancy reported in the elderly; use caution

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation

• CMV and EBV reactivation reported in aGVHD prophylaxis after hematopoietic cell transplant (HSCT)
• Post-transplant lymphoproliferative disorder (PTLD) occurred in patients who received drug for aGVHD prophylaxis during unrelated HSCT; all the PTLD events were associated with Epstein-Barr virus (EBV) infection; 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
• Cytomegalovirus (CMV) invasive disease reported in patients who received therapy for aGVHD prophylaxis during unrelated HSCT; monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of results of donor and recipient pre-transplant CMV serology; consider prophylaxis for CMV infection/reactivation

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to therapy during pregnancy; healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972

There are no adequate and well-controlled studies of use in pregnant women; data in pregnant women are insufficient to inform on drug-associated risk; however, there are clinical considerations for administering live vaccines to infants exposed to the drug while in utero

In reproductive toxicology studies in rats and rabbits, no fetal malformations were observed with intravenous administration during organogenesis at doses that produced exposures approximately 29 times the exposure at the maximum recommended human dose (MRHD) of 10 mg/kg/month on an AUC basis; however, in a pre-and postnatal development study in rats, therapy altered immune function in female rats at 11 times the MRHD on an AUC basis

It is unknown if abatacept can cross the placenta into the fetus when a woman is treated during pregnancy; the drug is an immunomodulatory agent; it is unknown if immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted; risks and benefits should be considered prior to vaccinating such infants

Lactation

There is no information regarding presence of abatacept in human milk, effects on breastfed infant, or effects on milk production; however, abatacept was present in the milk of lactating rats dosed with abatacept.

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Chimeric protein that inhibits T-lymphocyte activation

Pharmacokinetics

Half-life, Terminal: 13 days

Peak Plasma: 295 mcg/mL

Vd: 0.07 L/kg

Clearance: 0.22 mL/hr/kg

IV Compatibility

0.9% NaCl

IV Preparation

Reconstitution

• Reconstitute each vial contents with 10 mL sterile water for injection using ONLY the silicone-free disposable syringe supplied to obtain a 25 mg/mL solution
• If lyophilized powder is accidently reconstituted using a siliconized syringe, solution may develop a few translucent particles (discard any solutions prepared using siliconized syringes
• If silicone-free disposable syringe is dropped or becomes contaminated, use a new silicone-free disposable syringe; obtain new silicone-free syringes, contact BristolMyers Squibb at 1-800-ORENCIA
• Gently swirl vial to minimize foam formation, until contents are completely dissolved; do not shake; avoid prolonged or vigorous agitation
• Once completely dissolve, vent vial with a needle to dissipate any foam that may be present
• Visually inspect the reconstituted solution (the solution should be clear and colorless to pale yellow); discard if opaque particles, discoloration, or other foreign particles are present

Dilution

• Withdraw volume of 0.9% NaCl equal to calculated dose volume; final concentration of infusion ≤10 mg/mL
• Slowly add reconstituted solution from each vial into the infusion bag or bottle using the same disposable syringe
• Gently mix; avoid shaking infusion bag or bottle
• Discard any unused portion immediately
• Do not use if any discoloration or particulate matter present

IV Administration

Infuse with a sterile, nonpyrogenic, low-protein-binding filter (0.2-1.2 micron)

RA or PJIA: Infuse IV over 30 min

aGvHD: Infuse IV over 60 min

Finish infusion within 24 hr of reconstitution

Do not administer with any other drugs

SC Administration

Prefilled syringes and autoinjectors are intended for SC use only and are not for IV infusion

Remove prefilled syringe or autoinjector from refrigerator and equilibrate to room temperature before administration

Inspect visually for particulate matter and discoloration prior to administration; discard if particulate matter or discoloration observed; solution should appear clear and colorless to pale yellow

Inject full amount SC (ie, 1 mL)

Rotate injection site between abdomen (except for 2-inch area around navel), thigh, or outer area of upper arms (if administered by care giver)

May use same thigh for weekly injections, as long as each injection is at leat 1-inch away from the last area injected

Do not inject into areas where the skin is tender, bruised, red, or hard

Storage

Unused vials (lyophilized powder)

• Refrigerate at 2-8°C (36-46°F); protect from light by storing in original package until time of use

Dilute solutions

• Store at room temperature or refrigerated for up to 24 hr

Prefilled syringes or autoinjectors

• Refrigerate at 2-8°C (36-46°F); protect from light by storing in original package until time of use
• Do not allow prefilled syringe or autoinjector to freeze