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Abatacept

Pronunciation

(ab a TA sept)

Index Terms

  • BMS-188667
  • CTLA-4Ig

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous:

Orencia ClickJect: 125 mg/mL (1 mL)

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Orencia: 125 mg/mL (1 mL)

Solution Reconstituted, Intravenous [preservative free]:

Orencia: 250 mg (1 ea)

Brand Names: U.S.

  • Orencia
  • Orencia ClickJect

Pharmacologic Category

  • Antirheumatic, Disease Modifying
  • Selective T-Cell Costimulation Blocker

Pharmacology

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.

Distribution

Vss: 0.07 L/kg (range: 0.02 to 0.13 L/kg)

Half-Life Elimination

RA: 13.1 days (range: 8 to 25 days)

Clearance: 0.22 to 0.23 mL/hour/kg; Children 6 to 17 years: JIA: 0.4 mL/hour/kg (increases with baseline body weight)

Use: Labeled Indications

Rheumatoid arthritis: Treatment of moderately to severely active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs

Juvenile idiopathic arthritis: Treatment of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA); may be used as monotherapy or in combination with methotrexate

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: Hypersensitivity to abatacept or any component of the formulation; patients with, or at risk of sepsis syndrome (eg, immunocompromised, HIV positive)

Dosing: Adult

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

60-100 kg: 750 mg

>100 kg: 1000 mg

SubQ: 125 mg subcutaneously 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 (JIA): IV:

Children ≥6 years and <75 kg: 10 mg/kg (based on body weight at each administration), repeat dose at 2 weeks and 4 weeks after initial infusion, and every 4 weeks thereafter.

Children ≥6 years and ≥75 kg: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter:

75-100 kg: 750 mg

>100 kg: 1000 mg

Dosing: Renal Impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied).

Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer's labeling (has not been studied).

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). 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.

Compatibility

Stable in NS.

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, 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

Anakinra: May enhance the adverse/toxic effect of Abatacept. Avoid combination

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: Abatacept may enhance the adverse/toxic effect of Belimumab. 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

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

RiTUXimab: May enhance the adverse/toxic effect of Abatacept. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tocilizumab: May enhance the adverse/toxic effect of Abatacept. Avoid combination

Tofacitinib: Abatacept may enhance the adverse/toxic effect of Tofacitinib. Avoid combination

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. 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

Note: Percentages not always reported; 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

Respiratory: Nasopharyngitis (12%), upper respiratory tract infection

Miscellaneous: Infection (adults 54%; children 36%), antibody development (2% to 41%)

1% to 10%:

Cardiovascular: Hypertension (7%)

Central nervous system: Dizziness (9%)

Dermatologic: Skin rash (4%)

Gastrointestinal: Dyspepsia (6%), abdominal pain, diarrhea

Genitourinary: Urinary tract infection (6%)

Immunologic: Immunogenicity (1% to 2%)

Infection: Herpes simplex infection, influenza

Local: Injection site reaction (3%)

Neuromuscular & skeletal: Back pain (7%), limb pain (3%)

Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis

Miscellaneous: Infusion-related reaction (≤9%), fever

<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylactoid reaction, anaphylaxis, cellulitis, diverticulitis, dyspnea, exacerbation of arthritis, exacerbation of chronic obstructive pulmonary disease, hypersensitivity, hypotension, joint wear, malignant neoplasm (including malignant melanoma, malignant neoplasm of the bile duct, malignant neoplasm of bladder, malignant neoplasm of breast, malignant neoplasm of cervix, malignant neoplasm of kidney, malignant neoplasm of prostate, malignant neoplasm of skin, malignant neoplasm of thyroid, myelodysplastic syndrome, and uterine neoplasm), malignant neoplasm of lung, ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella, vasculitis (including hypersensitivity angiitis [cutaneous vasculitis and leukocytoclastic vasculitis]), wheezing

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. The manufacturer does not recommend concurrent use with anakinra or TNF-blocking agents.

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 Considerations

Adverse effects were not observed in animal studies. 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, nausea, signs of common cold, rhinitis, pharyngitis, abdominal pain, or back pain. Have patient report immediately to prescriber signs of infection, severe dizziness, passing out, severe headache, shortness of breath, skin growth, weight loss, night sweats, severe loss of strength and energy, flu-like symptoms, swelling, warmth, or redness of skin, or severe injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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