Abatacept

Name: Abatacept

What is the most important information I should know about abatacept?

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in the original container; protect from light.1

Store fully diluted solution at either room temperature or between 2–8°C.1 Infusion of diluted solution must be completed within 24 hours of reconstitution.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible

Sodium chloride 0.9%.1

Drug Compatibility

Information on the physical and/or chemical compatibility with other drugs is not available.1

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)

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 Pediatric

Juvenile idiopathic arthritis (JIA):

IV: Note: Dosage is according to body weight. Repeat dose at 2 weeks and 4 weeks after initial dose and every 4 weeks thereafter.

Children ≥6 years and <75 kg: 10 mg/kg

Children ≥6 years and ≥75 kg:

75 to 100 kg: 750 mg

>100 kg: 1,000 mg (maximum dose)

SubQ: Children ≥2 years, and Adolescents: Note: Administer without an IV loading dose and use weight-based dosing.

10 to <25 kg: 50 mg once weekly

≥25 to <50 kg: 87.5 mg once weekly

≥50 kg: 125 mg once weekly

Dosing Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

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.

What Is Orencia (Abatacept)?

Orencia is the brand name of the prescription drug abatacept, which is used to treat symptoms of rheumatoid arthritis (a condition in which the body's immune system attacks its own joints).

The medicine is also used to treat arthritis in children (juvenile idiopathic arthritis) who are at least 6 years old.

Orencia belongs to a class of drugs called selective costimulation modulators. It works by blocking the activity of the body's T-cells (immune cells that cause swelling and joint damage in people with arthritis).

The U.S. Food and Drug Administration (FDA) approved Orencia in 2005. It's manufactured by Bristol-Myers Squibb.

Orencia Warnings

Orencia can cause serious or life-threatening infections. Tell your doctor immediately if you experience symptoms of an infection, such as:

  • Fever
  • Chills
  • Dry cough or sore throat
  • Night sweats
  • Extreme tiredness
  • Weight loss
  • Warm, red, or painful skin

Before receiving Orencia, tell your doctor if you've ever had tuberculosis (TB), been around someone with TB, or traveled to an area where TB is common.

Let your doctor know if you've recently had, or plan on having, a vaccination. You shouldn't receive any vaccines while being treated with Orencia, or for three months after your treatment ends.

Because of this, it's a good idea to get all of your vaccinations that are due before starting Orencia.

Children who receive Orencia should be up-to-date on their vaccinations.

Try to avoid being around people who are sick or have infections while you're on Orencia.

Before receiving Orencia, let your doctor know if you have, or have ever had:

  • Any kind of infection (including sores and skin infections)
  • Diabetes
  • Hepatitis
  • Chronic obstructive pulmonary disease (COPD)
  • A condition that affects your nervous system, such as multiple sclerosis (MS)
  • A condition that affects your immune system, such as cancer, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS), or severe combined immunodeficiency (SCID)

Orencia may raise your risk of developing certain types of cancer, including lymphoma. This risk may be greater in older adults.

This medicine may cause a reaction shortly after it's given. Tell your doctor immediately if you experience any of the following symptoms within one hour of receiving Orencia:

  • Dizziness
  • Lightheadedness
  • Severe headache
  • Trouble breathing
  • Itching
  • Rash

Tell your healthcare provider that you're receiving Orencia before having any type of surgery, including a dental procedure.

Orencia may cause false results on certain blood glucose tests. If you have diabetes, talk to your doctor about what kind of test you should use to check your blood glucose level.

Pregnancy and Orencia

It's not known whether Orencia can harm an unborn baby. Tell your doctor if you're pregnant, or might become pregnant during your treatment.

It's also not known whether the medicine passes into breast milk or could hurt a breastfeeding baby.

Don't breastfeed while you're on Orencia.

Orencia Dosage

Orencia is given as an injection, or as an intravenous (IV) infusion.

Infusions by IV are typically administered by a healthcare professional in a clinic setting. They're usually given every two weeks for the first three doses, and then every four weeks after that.

Orencia should be given slowly when it's infused by IV. The process usually takes about 30 minutes.

You may be shown how to give yourself an injection of Orencia at home. These injections are usually given once a week.

Follow your doctor's instructions carefully when injecting Orencia. Don't give yourself more or less of the medicine than is recommended.

Don't use Orencia if the medicine has changed color or has particles in it.

You may need to mix Orencia with a liquid before injecting it. Follow your doctor's instructions carefully.

Orencia Overdose

If you suspect an overdose of Orencia, contact a poison control center or emergency room immediately.

You can get in touch with a poison control center at 800-222-1222.

Missed Dose of Orencia

Call your doctor for instructions if you miss a dose of Orencia.

What is abatacept, and how does it work (mechanism of action)?

Abatacept is an injectable, synthetic (man-made) protein produced by recombinant DNA technology that is used for treating rheumatoid arthritis. It is an immunesuppressant, a drug that suppresses the immune system that is similar to alefacept (Amevive) and belatacept (Nulojix). The immune system is responsible for protecting the body against foreign invaders, for example, infectious agents such as bacteria. In patients with rheumatoid arthritis, however, the immune system attacks and destroys normal tissue in and around the joints, causing pain, inflammation and damage to bone and cartilage. T-lymphocytes are important cells of the immune system. Patients with rheumatoid arthritis have increased numbers of T-lymphocytes within the joints that are inflamed. The T-lymphocytes are "activated," that is, they multiply and release chemicals that promote the destruction of tissues surrounding the joints and cause the signs and symptoms of rheumatoid arthritis. Abatacept acts like an antibody and attaches to a protein on the surface of T-lymphocytes. By attaching to the protein, abatacept prevents the activation of the T-lymphocytes and blocks both the production of new T-lymphocytes and the production of the chemicals that destroy tissue and cause the symptoms and signs of arthritis. Abatacept relieves the symptoms and signs of arthritis and is a disease-modifying antirheumatic drug (DMARD) because it slows the damage to bones and cartilage and improves physical function. Abatacept was approved by the FDA in December 2005.

Is abatacept safe to take if I'm pregnant or breastfeeding?

Abatacept has not been adequately evaluated in pregnant women.

Abatacept has not been adequately evaluated in women who are breastfeeding.

Description

ORENCIA® (abatacept) is a selective T cell costimulation modulator. ORENCIA is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) linked to the modified Fc (hinge, CH2, and CH3 domains) portion of human immunoglobulin G1 (IgG1). Abatacept is produced by recombinant DNA technology in a mammalian cell expression system. The apparent molecular weight of abatacept is 92 kilodaltons.

ORENCIA for Injection is a lyophilized powder for intravenous infusion. ORENCIA for Injection is supplied as a sterile, white, preservative-free, lyophilized powder for reconstitution and dilution prior to intravenous administration. Following reconstitution of the lyophilized powder with 10 mL of Sterile Water for Injection, USP, the solution of ORENCIA is clear, colorless to pale yellow, with a pH range of 7.2 to 7.8. Each single-use vial of ORENCIA for Injection provides 250 mg abatacept, maltose (500 mg), monobasic sodium phosphate (17.2 mg), and sodium chloride (14.6 mg) for administration.

ORENCIA Injection is a sterile, preservative-free, clear to slightly opalescent, colorless to paleyellow solution with a pH range of 6.8 to 7.4 for subcutaneous administration. ORENCIA Injection is supplied as a single-dose prefilled syringe or as a single-dose ClickJect autoinjector (see Table 4).

Table 4: Contents of ORENCIA Subcutaneous Injection

Presentation Active Ingredient Quantity and Label Volume Inactive Ingredient Content
ORENCIA Injection 50 mg/0.4 mL Prefilled Syringe 50 mg of abatacept in 0.4 mL of solution dibasic sodium phosphate anhydrous (0.335 mg) monobasic sodium phosphate monohydrate (0.114 mg) poloxamer 188 (3.2 mg) sucrose (68 mg) qs to 0.4 mL water for injection
ORENCIA Injection 87.5 mg/0.7 mL Prefilled Syringe 87.5 mg of abatacept in 0.7 mL of solution dibasic sodium phosphate anhydrous (0.587 mg) monobasic sodium phosphate monohydrate (0.200 mg) poloxamer 188 (5.6 mg) sucrose (119 mg) qs to 0.7 mL water for injection

Unlike the lyophilized formulation for intravenous use, the ORENCIA solutions for subcutaneous administration contain no maltose.

Abatacept Usage

  • You may receive abatacept given by a healthcare provider through a vein in your arm (IV or intravenous infusion). It takes about 30 minutes to give you the full dose of medicine. You will then receive abatacept 2 weeks and 4 weeks after the first dose and then every 4 weeks.
  • You may also receive abatacept as an injection under your skin (subcutaneous). If your healthcare provider decides that you or a caregiver can give your injections of abatacept at home, you or your caregiver should receive training on the right way to prepare and inject abatacept. Do not try to inject abatacept until you have been shown the right way to give the injections by your healthcare provider.
  • Your healthcare provider will tell you how much abatacept to use and when to use it.

What should i discuss with my healthcare provider before using abatacept (orencia)?

You should not use abatacept if you are allergic to it, or if you are also using anakinra (Kineret), etanercept (Enbrel), adalimumab (Humira), certolizumab (Cimzia), golimumab (Simponi), infliximab (Remicade), natalizumab (Tysabri), rituximab (Rituxan), or tocilizumab (Actemra).

Before using abatacept, tell your doctor if you have ever had tuberculosis, if anyone in your household has tuberculosis, or if you have recently traveled to an area where tuberculosis is common.

To make sure you can safely use abatacept, tell your doctor if you have any of these other conditions:

  • a weak immune system;
  • any type of infection including a skin infection or open sores;
  • COPD (chronic obstructive pulmonary disease);
  • diabetes;
  • if you have ever had hepatitis; or
  • if you are scheduled to receive any vaccines.

FDA pregnancy category C. It is not known whether abatacept will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of abatacept on the baby.

It is not known whether abatacept passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using abatacept.

Children using this medication should be current on all childhood immunizations before starting treatment with abatacept.

Using abatacept may increase your risk of developing certain types of cancer such as lymphoma (cancer of the lymph nodes). This risk may be greater in older adults. Talk to your doctor about your specific risk.

Where can i get more information?

Your doctor or pharmacist can provide more information about abatacept.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 6.01. Revision date: 9/19/2011.

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In Summary

Commonly reported side effects of abatacept include: headache and nasopharyngitis. Other side effects include: dyspepsia and hypertension. See below for a comprehensive list of adverse effects.

For Healthcare Professionals

Applies to abatacept: intravenous powder for injection, subcutaneous solution

Respiratory

Very common (10% or more): Upper respiratory tract infection (including tracheitis, nasopharyngitis)
Common (1% to 10%): Lower respiratory tract infection (including bronchitis), rhinitis, pneumonia, cough, sinusitis
Uncommon (0.1% to 1%): Bronchospasm, wheezing, dyspnea
Rare (less than 0.1%): Throat tightness, bacterial pneumonia, influenza pneumonia
Frequency not reported: Tracheitis[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Hypersensitivity[Ref]

Oncologic

Frequency not reported: Cancer of lung, skin, breast, bile duct, bladder, cervical, endometrial, lymphoma, melanoma, myelodysplastic syndrome, ovarian, prostate, renal, thyroid, uterus[Ref]

Immunologic

Common (1% to 10%): Herpes infections (including herpes simplex, oral herpes, and herpes zoster), influenza
Uncommon (0.1% to 1%): Streptococcal sepsis
Rare (less than 0.1%): Tuberculosis, bacteremia[Ref]

Gastrointestinal

Common (1% to 10%): Abdominal pain, diarrhea, nausea, dyspepsia, mouth ulceration, aphthous stomatitis, vomiting
Uncommon (0.1% to 1%): Tooth infection, gastritis, weight increased
Rare (less than 0.1%): Gastrointestinal infection, diverticulitis, peridiverticular abscess[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infection
Uncommon (0.1% to 1%): Pelvic inflammatory disease, amenorrhea, menorrhagia[Ref]

Dermatologic

Common (1% to 10%): Rash (including dermatitis), alopecia, pruritus
Uncommon (0.1% to 1%): Onychomycosis, skin abscess
Frequency not reported: Dry skin, cellulitis, increased tendency to bruise, infected skin ulcers[Ref]

Nervous system

Very common (10% or more): Headache (12%)
Common (1% to 10%): Dizziness, paresthesia
Uncommon (0.1% to 1%): Migraine
Frequency not reported: Vertigo[Ref]

Local

Common (1% to 10%): Local injection site reactions[Ref]

Cardiovascular

Common (1% to 10%): Hypertension, flushing
Uncommon (0.1% to 1%): Palpitations, tachycardia, bradycardia, hypotension, hot flush, vasculitis, hypotension[Ref]

Hepatic

Common (1% to 10%): Liver function test abnormal (including transaminases increased)
Frequency not reported: abnormal liver function tests and increased transaminases[Ref]

Hematologic

Common (1% to 10%): Leukopenia
Uncommon (0.1% to 1%): Thrombocytopenia[Ref]

Metabolic

Frequency not reported: Weight gain[Ref]

Musculoskeletal

Common (1% to 10%): Pain in extremity
Uncommon (0.1% to 1%): Musculoskeletal infections, arthralgia[Ref]

Ocular

Common (1% to 10%): Conjunctivitis
Uncommon (0.1% to 1%): Dry eye, visual acuity reduced[Ref]

Psychiatric

Uncommon (0.1% to 1%): Depression, anxiety, sleep disorder (including insomnia)[Ref]

Renal

Uncommon (0.1% to 1%): Pyelonephritis[Ref]

Some side effects of abatacept may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Liver Dose Adjustments

Data not available

Abatacept Pregnancy Warnings

Use is not recommended unless clearly needed. AU TGA pregnancy category: C US FDA pregnancy category: Not assigned. Risk Summary: The data concerning the use of this drug in pregnant women are insufficient to inform on drug-associated risk. In reproductive toxicology studies in animals, no fetal malformations were observed with IV 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 animals, this drug altered immune function in females at 11 times the MRHD on an AUC basis. Comments: -Women of child-bearing potential should use effective contraception during treatment with this drug and up to 14 weeks after the last dose. -Administration of live vaccines to infants exposed to this drug in utero is not recommended for 5 months following the mother's last dose.

-Animal studies have failed to reveal evidence of teratogenicity or fetotoxicity. There are no controlled data in human pregnancy. -Rats treated with this drug every 3 days during early gestation throughout the lactation period showed no adverse effects in the offspring at doses up to 45 mg/kg (3-fold a human 10 mg/kg dose based on AUC). At a dose of 200 mg/kg (11-fold a human 10 mg/kg dose based on AUC) alterations of immune function consisted of a 9-fold increase in the T-cell dependent antibody response in female pups and inflammation of the thyroid in one female pup out of 10 males and 10 females evaluated. It has not been determined if these findings indicate a risk for development of autoimmune diseases in humans exposed in utero. -This drug crosses the placenta into the serum of infants born to women treated during pregnancy; these infants may be at increased risk for infection. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

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