Abatacept – Drug information

Abatacept: Drug information
Copyright 1978-2011 Lexicomp, Inc. All rights reserved.
(For additional information see “Abatacept: Patient drug information” and see “Abatacept: Pediatric drug information”)

Brand Names: U.S. Orencia®
Brand Names: Canada Orencia®
Pharmacologic Category Antirheumatic, Disease Modifying; Selective T-Cell Costimulation Blocker
Dosing: Adult Rheumatoid arthritis (RA): I.V.: Dosing is according to body weight:
<60 kg: 500 mg

60-100 kg: 750 mg

>100 kg: 1000 mg

I.V. regimen: Following the initial I.V. infusion, repeat I.V. dose (using the same weight-based dosing) at 2 weeks and 4 weeks after the initial infusion, and every 4 weeks thereafter.

SubQ regimen: Following the initial I.V. infusion (using the weight-based dosing), administer 125 mg subcutaneously within 24 hours of the infusion, followed by 125 mg subcutaneously once weekly thereafter. Note: Patients unable to receive I.V. infusions may omit the initial I.V. loading dose and initiate once weekly SubQ therapy directly.

Transitioning from I.V. therapy to SubQ therapy: Administer the first SubQ dose instead of the next scheduled I.V. dose.

Dosing: Pediatric
(For additional information see “Abatacept: Pediatric drug information”)

Juvenile idiopathic arthritis (JIA): I.V.:
Children ≥6 years and <75 kg: 10 mg/kg, repeat dose at 2 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: Geriatric Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.
Dosing: Adjustment for Toxicity Discontinue in patients who develop a serious infection.
Dosage Forms: U.S. Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution [preservative free]:

Orencia®: 250 mg [contains maltose]

Generic Equivalent Available: U.S. No
Product Availability
Orencia® 125 mg/mL prefilled syringe: FDA approved August 2011; availability expected in September 2011

Orencia® 125 mg/mL prefilled syringe is a subcutaneously administered once-weekly formulation approved for the treatment of adult rheumatoid arthritis.

Administration
I.V.: Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter

SubQ: Allow prefilled syringe to warm to room temperature (for 30-60 minutes) 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.
Use
Treatment of moderately- to severely-active adult rheumatoid arthritis (RA); may be used as monotherapy or in combination with other DMARDs

Treatment of moderately- to severely-active 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

Medication Safety Issues
Sound-alike/look-alike issues:
Orencia® may be confused with Oracea®

Adverse Reactions Significant 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 formation (2% to 41%)

1% to 10%:

Cardiovascular: Hypertension (7%)

Central nervous system: Dizziness (9%), fever

Dermatologic: Rash (4%)

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

Genitourinary: Urinary tract infection (6%)

Local: Injection site reaction (3%)

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

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

Miscellaneous: Infusion-related reactions (≤9%), herpes simplex, immunogenicity (1% to 2%), influenza

<1% (Limited to important or life-threatening): Acute lymphocytic leukemia, anaphylaxis, anaphylactoid reactions, cellulitis, COPD exacerbation, disease flare, diverticulitis, dyspnea, flushing, hypersensitivity, hypotension, joint wear, lung cancer, lymphoma; malignancies (including bile duct, bladder, breast, cervical, melanoma, myelodysplastic syndrome, prostate, renal, skin, thyroid and uterine); ovarian cyst, pruritus, pyelonephritis, rhonchi, urticaria, varicella infection, vasculitis (including cutaneous vasculitis and leukocytoclastic vasculitis), wheezing

Contraindications There are no contraindications listed within the FDA-approved labeling.
Warnings/Precautions
Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Rare cases of hypersensitivity, anaphylaxis, or anaphylactoid reactions have been reported; 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. 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:

• Anakinra: The manufacturer does not recommend concurrent use with anakinra.

• TNF-blocking agents: Adult patients receiving therapy in combination with TNF-blocking agents had higher rates of infections (including serious infections) than patients on TNF-blocking agents alone. Concurrent use with TNF-blocking agents is not recommended. Monitor for signs and symptoms of infection when transitioning from TNF-blocking agents to abatacept.

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.

Drug Interactions
(For additional information: Launch Lexi-Interact™ Drug Interactions Program )
Anti-TNF Agents: May enhance the adverse/toxic effect of Abatacept. An increased risk of serious infection during concomitant use has been reported. Risk X: Avoid combination

BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination

Belimumab: Abatacept may enhance the adverse/toxic effect of Belimumab. Risk X: Avoid combination

Coccidioidin Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioidin Skin Test. Risk C: Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: 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. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination

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

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

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

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

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. 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. Risk X: Avoid combination

Ethanol/Nutrition/Herb Interactions Herb/Nutraceutical: Avoid echinacea (has immunostimulant properties; consider therapy modifications).
Pregnancy Risk Factor C (show table)
Pregnancy Implications Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women. Due to the potential risk for development of autoimmune disease in the fetus, use during pregnancy only if clearly needed. A pregnancy registry has been established to monitor outcomes of women exposed to abatacept during pregnancy (1-877-311-8972).
Lactation Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations Due to the potential for adverse reactions and possible effects on the developing immune system, breast-feeding is not recommended.
Pricing: U.S. (www.drugstore.com)
Solution (reconstituted) (Orencia)

250 mg (1): $606.98

Monitoring Parameters Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation
International Brand Names Orencia (AR, AU, BE, BR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, GR, HK, HN, IE, IL, IT, NL, NO, NZ, PE, PL, PT, SE, SG, TW)
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.
Pharmacodynamics/Kinetics
Bioavailability: SubQ: 78.6% (relative to I.V. administration)

Distribution: Vss: 0.02-0.13 L/kg

Half-life elimination: 8-25 days

REFERENCES
Doan T and Massarotti E, “Rheumatoid Arthritis: An Overview of New and Emerging Therapies,” J Clin Pharmacol, 2005, 45(7):751-62. [PubMed 15951465]
Furst DE, Breedveld FC, Kalden JR, et al, “Updated Consensus Statement on Biological Agents for the Treatment of Rheumatic Diseases, 2007,” Ann Rheum Dis, 2007, 66(Suppl 3):2-22. [PubMed 17934088]
Genovese MC, Becker JC, Schiff M, et al, “Abatacept for Rheumatoid Arthritis Refractory to Tumor Necrosis Factor Alpha Inhibition,” N Engl J Med, 2005, 353(11):1114-23. [PubMed 16162882]
Kremer JM, Dougados M, Emery P, et al, “Treatment of Rheumatoid Arthritis With the Selective Costimulation Modulator Abatacept: Twelve-Month Results of a Phase IIb, Double-Blind, Randomized, Placebo-Controlled Trial,” Arthritis Rheum, 2005, 52(8):2263-71. [PubMed 16052582]
Kremer JM, Genant HK, Moreland LW, et al, “Effects of Abatacept in Patients With Methotrexate-Resistant Active Rheumatoid Arthritis: A Randomized Trial,” Ann Intern Med, 2006, 144(12):865-76. [PubMed 16785475]
Kremer JM, Westhovens R, Leon M, et al, “Treatment of Rheumatoid Arthritis by Selective Inhibition of T-Cell Activation With Fusion Protein CTLA4Ig,” N Engl J Med, 2003, 349(20):1907-15. [PubMed 14614165]
Tay L, Leon F, Vratsanos G, et al, “Vaccination Response to Tetanus Toxoid and 23-Valent Pneumococcal Vaccines Following Administration of a Single Dose of Abatacept: A Randomized, Open-Label, Parallel Group Study in Healthy Subjects,” Arthritis Res Ther, 2007, 9(2): R38. [PubMed 17425783]
Weinblatt M, Combe B, Covucci A, et al, “Safety of the Selective Costimulation Modulator Abatacept in Rheumatoid Arthritis Patients Receiving Background Biologic and Nonbiologic Disease-Modifying Antirheumatic Drugs: A One-Year Randomized, Placebo-Controlled Study,” Arthritis Rheum, 2006, 54(9):2807-16. [PubMed 16947384]