Orencia

U.S. BRAND NAMES — Orencia®

PHARMACOLOGIC CATEGORY
Antirheumatic, Disease Modifying

DOSING: ADULTS — Rheumatoid arthritis: I.V.: Dosing is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose, and every 4 weeks thereafter:
<60 kg: 500 mg
60-100 kg: 750 mg
>100 kg: 1000 mg

DOSING: PEDIATRIC — JIA: I.V.:

(For additional information see "Abatacept: Pediatric drug information")

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: ELDERLY — Refer to adult dosing. Due to potential for higher rates of infections and malignancies, use caution.

DOSING: ADJUSTMENT FOR TOXICITY — Withhold therapy for patients with serious infections.

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

Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg [contains maltose]

DOSAGE FORMS: CONCISE
Injection, powder for reconstitution [preservative free]:
Orencia®: 250 mg

GENERIC EQUIVALENT AVAILABLE — No

ADMINISTRATION — Infuse over 30 minutes. Administer through a 0.2-1.2 micron low protein-binding filter

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

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%)
Neuromuscular & skeletal: Back pain (7%), limb pain (3%)
Respiratory: Cough (8%), bronchitis, pneumonia, rhinitis, sinusitis
Miscellaneous: Infusion-related reactions (2% to 9%), herpes simplex, 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, 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: Caution should be exercised when considering the use in patients 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. Pediatrics: Not FDA approved for use in children <6 years of age. 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: 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
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

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

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). 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 — (data from drugstore.com)
Solution (reconstituted) (Orencia)
250 mg (1): $528.09

MONITORING PARAMETERS — Signs and symptoms of infection, signs and symptoms of infusion reaction; hepatitis and TB screening prior to therapy initiation

CANADIAN BRAND NAMES — Orencia®

INTERNATIONAL BRAND NAMES — Orencia (AR, CH, CN, CO, CZ, DE, DK, EE, FR, GB, IE, NO, PE, SE)

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
Distribution: Vss: 0.02-0.13 L/kg

Half-life elimination: 8-25 days

PATIENT INFORMATION — This drug can only be administered by infusion. Do not have any vaccinations while using this medication without consulting prescriber first. You will be more prone to infection. Avoid crowds and wash your hands frequently. Report infections (local or in your whole body) to prescriber immediately. You will need an overall health assessment prior to each treatment to ensure that you do not have an active infection. You may experience headache or dizziness (use caution when driving) or nausea (small frequent meals or sucking lozenges may help).