Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous [preservative free]:
Orencia ClickJect: 125 mg/mL (1 mL)
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Orencia: 50 mg/0.4 mL (0.4 mL); 87.5 mg/0.7 mL (0.7 mL); 125 mg/mL (1 mL)
Solution Reconstituted, Intravenous [preservative free]:
Orencia: 250 mg (1 ea)
Pharmacology
Mechanism of Action
Selective costimulation modulator; inhibits T-cell (T-lymphocyte) activation by binding to CD80 and CD86 on antigen presenting cells (APC), thus blocking the required CD28 interaction between APCs and T cells. Activated T lymphocytes are found in the synovium of rheumatoid arthritis patients.
Pharmacokinetics/Pharmacodynamics
Distribution
Vss: Rheumatoid arthritis: IV: 0.07 L/kg (range: 0.02 to 0.13 L/kg).
Half-Life Elimination
Rheumatoid arthritis (RA): IV: 13.1 days (range: 8 to 25 days).
Clearance: Note: Clearance increases with increasing body weight.
Children 6 to 17 years: Juvenile idiopathic arthritis: 0.4 mL/hour/kg (0.2 to 1.12 mL/hour/kg).
Adults: RA: 0.22 mL/hour/kg (0.13 to 0.47 mL/hour/kg).
Use: Labeled Indications
Juvenile idiopathic arthritis: Treatment of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate
Psoriatic arthritis: Treatment of active psoriatic arthritis (PsA) in adults
Rheumatoid arthritis: Treatment of moderately to severely active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs
Note: Abatacept should not be used in combination with anakinra or TNF-blocking agents
Contraindications
There are no contraindications listed within the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to abatacept or any component of the formulation; patients with, or at risk of sepsis syndrome (eg, immunocompromised, HIV positive)
Dosage and Administration
Dosing: Adult
Psoriatic arthritis (PsA):
IV: Dosing is according to body weight. Following the initial IV infusion (using the weight-based dosing), repeat IV infusion (using the same weight-based dosing) at 2 weeks and 4 weeks after the initial infusion, and every 4 weeks thereafter.
<60 kg: 500 mg
60 to 100 kg: 750 mg
>100 kg: 1,000 mg
SubQ: 125 mg once weekly. Note: Administer without an IV loading dose.
If transitioning from IV therapy to SubQ therapy, administer the first SubQ dose instead of the next scheduled IV dose.
Rheumatoid arthritis (RA):
IV: Dosing is according to body weight. Following the initial IV infusion (using the weight-based dosing), repeat IV infusion (using the same weight-based dosing) at 2 weeks and 4 weeks after the initial infusion, and every 4 weeks thereafter.
<60 kg: 500 mg
60 to 100 kg: 750 mg
>100 kg: 1,000 mg
SubQ: 125 mg once weekly. Note: SubQ dosing may be initiated with or without an IV loading dose.
If initiating with an IV loading dose, administer the initial IV 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.
If transitioning from IV therapy to SubQ therapy, administer the first SubQ dose instead of the next scheduled IV dose.
Dosing: Geriatric
Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
Dosing: Pediatric
Juvenile idiopathic arthritis: Note: Dosing varies by route of administration (IV or SubQ); use extra precaution.
IV: Children ≥6 years and Adolescents: Note: Dose is based on body weight at each dose administration. Following the initial IV infusion, repeat IV dose at 2 weeks and 4 weeks after the initial infusion, and every 4 weeks thereafter.
Patient weight:
<75 kg: IV: 10 mg/kg.
75 to 100 kg: IV: 750 mg.
>100 kg: IV: 1,000 mg.
SubQ: Children ≥2 years and Adolescents: Note: Administer without an IV loading dose and use the following weight-based dosing. The autoinjector for subcutaneous injection has not been studied in patients under 18 years of age.
Patient weight:
10 to <25 kg: SubQ: 50 mg once weekly.
≥25 to <50 kg: SubQ: 87.5 mg once weekly.
≥50 kg: SubQ: 125 mg once weekly.
Dosing adjustment for toxicity: Children ≥2 years and Adolescents: Discontinue in patients who develop serious infection.
Dosing: Adjustment for Toxicity
Discontinue in patients who develop a serious infection.
Reconstitution
IV: Reconstitute each vial with 10 mL SWFI using the provided silicone-free disposable syringe (discard solutions accidentally reconstituted with siliconized syringe as they may develop translucent particles) and an 18- to 21-gauge needle. Inject SWFI down the side of the vial to avoid foaming. The reconstituted solution contains 25 mg/mL abatacept. Further dilute (using a silicone-free syringe) in 100 mL NS to a final concentration of ≤10 mg/mL. Prior to adding abatacept to the 100 mL bag, the manufacturer recommends withdrawing a volume of NS equal to the abatacept volume required, resulting in a final volume of 100 mL. Mix gently; do not shake.
SubQ: Allow prefilled syringe to reach room temperature prior to administration by removing from refrigerator 30-60 minutes prior to administration.
Administration
IV: Infuse over 30 minutes. Administer through a 0.2 to 1.2 micron low protein-binding filter
SubQ: Allow prefilled syringe and autoinjector to warm to room temperature (for 30 to 60 minutes and 30 minutes, respectively) 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.
Storage
Prefilled syringe: Store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light.
Powder for injection: Prior to reconstitution, store at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. After dilution in NS, may be stored for up to 24 hours at room temperature or refrigerated at 2°C to 8°C (36°F to 46°F). Must be used within 24 hours of reconstitution.
Drug Interactions
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Avoid combination
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Belimumab: May enhance the immunosuppressive effect of Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination
Biologic Disease-Modifying Antirheumatic Drugs (DMARDs): May enhance the immunosuppressive effect of other Biologic Disease-Modifying Antirheumatic Drugs (DMARDs). Avoid combination
Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification
Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination
Test Interactions
Contains maltose; may result in falsely elevated blood glucose levels with dehydrogenase pyrroloquinolinequinone or glucose-dye-oxidoreductase testing methods on the day of infusion. Glucose monitoring methods which utilize glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase, or glucose hexokinase are recommended.
Adverse Reactions
COPD patients experienced a higher frequency of COPD-related adverse reactions (COPD exacerbation, cough, dyspnea, pneumonia, rhonchi).
>10%:
Central nervous system: Headache (18%)
Gastrointestinal: Nausea (≥10%)
Immunologic: Antibody development (2% to 41%)
Infection: Infection (54%), influenza (5% to 13%)
Respiratory: Bronchitis (5% to 13%), sinusitis (5% to 13%), upper respiratory tract infection (5% to 13%), nasopharyngitis (12%)
1% to 10%:
Cardiovascular: Hypertension (7%)
Central nervous system: Dizziness (9%)
Dermatologic: Skin rash (4%)
Gastrointestinal: Dyspepsia (6%)
Genitourinary: Urinary tract infection (6%)
Immunologic: Immunogenicity (1% to 2%)
Infection: Herpes simplex infection (<5%)
Local: Injection site reaction (3% to 4%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), pneumonia (<5%), rhinitis (<5%)
Miscellaneous: Infusion-related reaction (≤9%)
<1% and/or case reports: Anaphylaxis, cellulitis, diverticulitis of the gastrointestinal tract, dyspnea, flushing, hypersensitivity reaction, hypotension, malignant lymphoma, malignant neoplasm of lung, nonimmune anaphylaxis, pruritus, pyelonephritis, sepsis, urticaria, wheezing
Frequency not defined:
Genitourinary: Malignant neoplasm of cervix
Hematologic & oncologic: Endometrial carcinoma, malignant melanoma, malignant neoplasm of the bile duct, malignant neoplasm of bladder, malignant neoplasm of breast, malignant neoplasm of kidney, malignant neoplasm of ovary, malignant neoplasm of prostate, malignant neoplasm of skin, malignant neoplasm of thyroid, malignant neoplasm of uterus, myelodysplastic syndrome
Respiratory: Exacerbation of chronic obstructive pulmonary disease, rhonchi
Postmarketing: Exacerbation of psoriasis, hypersensitivity angiitis, psoriasis, vasculitis
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported with intravenous administration; may occur with first infusion. Some reactions (hypotension, urticaria, dyspnea) occurred within 24 hours of infusion. Discontinue treatment if anaphylaxis or other serious allergic reaction occurs; medication for the treatment of hypersensitivity reactions should be available for immediate use.
- Infections: Serious and potentially fatal infections (including tuberculosis and sepsis) have been reported, particularly in patients receiving concomitant immunosuppressive therapy. RA patients receiving a concomitant TNF antagonist experienced an even higher rate of serious infection; monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept. Caution should be exercised when considering the use in any patient with a history of new/recurrent infections, with conditions that predispose them to infections, or with chronic, latent, or localized infections. Patients who develop a new infection while undergoing treatment should be monitored closely. If a patient develops a serious infection, therapy should be discontinued.
- Malignancy: Use may affect defenses against malignancies (via T cell inhibition); impact on the development and course of malignancies is not fully defined. As compared to the general population, an increased risk of lymphoma and lung cancer has been noted in clinical trials; however, rheumatoid arthritis has been previously associated with an increased rate of lymphoma.
Disease-related concerns:
- COPD: Use caution with chronic obstructive pulmonary disease (COPD), higher incidences of adverse effects (COPD exacerbation, cough, rhonchi, dyspnea) have been observed; monitor closely.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Elderly: Use with caution, higher incidences of infection and malignancy were observed in the elderly.
- Tuberculosis-positive patients: Safety has not been established in tuberculosis-positive patients; screen patients for latent tuberculosis infection prior to initiating therapy. Treat patients testing positive according to standard therapy prior to initiating abatacept.
Dosage form specific issues:
- Maltose: Powder for injection may contain maltose, which may result in falsely-elevated serum glucose readings on the day of infusion.
Other warnings/precautions:
- Hepatitis screening: Patients should be screened for viral hepatitis prior to use; antirheumatic therapy may cause reactivation of hepatitis B.
- Immunizations: Patients should be brought up to date with all immunizations before initiating therapy. Live vaccines should not be given concurrently or within 3 months of discontinuation of therapy; there is no data available concerning secondary transmission of live vaccines in patients receiving therapy.
Monitoring Parameters
Signs and symptoms of infection, signs and symptoms of hypersensitivity reaction; hepatitis and TB screening prior to therapy initiation
Pregnancy
Pregnancy Considerations
Information related to the use of abatacept in pregnancy is limited (Kumar 2015). Until additional data are available, it is recommended to discontinue use and switch to a safer medication prior to conception unless no other pregnancy compatible medication is able to control maternal disease (Götestam Skorpen 2016).
A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
Patient Education
What is this drug used for?
- It is used to treat rheumatoid arthritis.
- It is used to treat juvenile arthritis.
- It is used to treat psoriatic arthritis.
- It may be given to you for other reasons. Talk with the doctor.
Frequently reported side effects of this drug
- Diarrhea
- Nausea
- Injection site irritation
- Common cold
- Stuffy nose
- Sore throat
- Abdominal pain
- Back pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- Severe dizziness
- Passing out
- Severe headache
- Vision changes
- Shortness of breath
- Skin growth
- Weight loss
- Night sweats
- Severe loss of strength and energy
- Flu-like symptoms
- Pain, warmth, or redness of skin
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
