Orencia

Common Side Effects of Orencia

Tell your doctor if any of the following symptoms become severe or don't go away:

• Headache
• Runny nose or sore throat
• Nausea
• Mild dizziness
• Heartburn
• Back pain
• Leg or arm pain

Serious Side Effects of Orencia

Tell your doctor right away if you experience any of the symptoms listed in the Orencia Warnings section above, or any of the following serious side effects:

• Hives or skin rash
• Swelling of the face, eyes, lips, throat, or tongue
• Shortness of breath
• Chest pain
• Frequent urination, or a sudden need to urinate right away
• Burning sensation during urination

Yes

Adult Rheumatoid Arthritis (RA)

ORENCIA® is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. ORENCIA may be used as monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) other than tumor necrosis factor (TNF) antagonists.

Juvenile Idiopathic Arthritis

ORENCIA is indicated for reducing signs and symptoms in patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis. ORENCIA may be used as monotherapy or concomitantly with methotrexate (MTX).

Adult Psoriatic Arthritis (PsA)

ORENCIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).

Important Limitations Of Use

ORENCIA should not be administered concomitantly with TNF antagonists. ORENCIA is not recommended for use concomitantly with other biologic rheumatoid arthritis (RA) therapy, such as anakinra.

>10%

Headache (18%)

Nasopharyngitis (12%)

Nausea (>10%)

Infection (54% for adults & 36% for children)

1-10%

Dizziness (9%)

Cough (8%)

Back pain (7%)

Hypertension (7%)

Dyspepsia (6%)

Urinary Tract Infection (6%)

Rash (4%)

Pain in extremety (3%)

< 1%

Acute lymphocytic leukemia

Anaphylaxis

Cellulitis

COPD exacerbation

Disease flare

Diverticulitis

Dyspnea

Flushing

Hypersensitivity

Hypotension

Joint wear

Lung cancer

Lymphoma

Malignancies

Ovarian cyst

Pruitus

Pyelonephritis

Rhonchi

Urticaria

Varicella infection

Wheezing

Frequency Not Defined

Nausea

Abdominal pain

Diarrhea

Abatacept is a man-made protein that prevents your body's immune system from attacking healthy tissues such as joints. The immune system helps your body fight infections. In people with autoimmune disorders, the immune system mistakes the body's own cells for invaders and attacks them.

Abatacept is used to treat the symptoms of rheumatoid arthritis, and to prevent joint damage caused by these conditions. It is also used to treat arthritis in children who are at least 6 years old.

Abatacept is not a cure for any autoimmune disorder and will only treat the symptoms of your condition.

Abatacept may also be used for purposes not listed in this medication guide.

Biologic response modifier and disease-modifying antirheumatic drug (DMARD); a recombinant fusion protein.1 2 3 4 5

Rheumatoid Arthritis

Used to manage the signs and symptoms of rheumatoid arthritis, to induce a major clinical response, to improve physical function, and to inhibit progression of structural damage associated with the disease in adults with moderate to severe active rheumatoid arthritis.1 2 3 4 5 Can be used alone or with other DMARDs other than tumor necrosis factor (TNF) blocking agents.1

Do not use concomitantly with TNF blocking agents (e.g., adalimumab, certolizumab pegol, etanercept, infliximab); concomitant use with other biologic antirheumatic drugs (e.g., anakinra) not recommended.1 (See Infectious Complications under Cautions and see Specific Drugs and Laboratory Tests under Interactions.)

Juvenile Arthritis

Management of the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in children.1 7 Can be use alone or with methotrexate.1

Do not use concomitantly with TNF blocking agents (e.g., adalimumab, certolizumab pegol, etanercept, infliximab); concomitant use with other biologic antirheumatic drugs (e.g., anakinra) not recommended.1 (See Infectious Complications under Cautions and see Specific Drugs and Laboratory Tests under Interactions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Back pain
• bladder pain
• bloody or cloudy urine
• body aches or pain
• chills
• cough
• cough producing mucus
• difficult or labored breathing
• difficult, burning, or painful urination
• dizziness
• ear congestion
• fever
• frequent urge to urinate
• headache
• loss of voice
• lower back or side pain
• nausea or vomiting
• noisy breathing
• pain or tenderness around the eyes and cheekbones
• sneezing
• sore throat
• stuffy or runny nose
• tightness of the chest
• troubled breathing
• unusual tiredness or weakness

• Blurred vision
• burning or stinging of the skin
• chest pain
• nervousness
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pounding in the ears
• skin rash
• slow or fast heartbeat

• Confusion
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• flushing
• hives or welts
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• stomach pain or tenderness
• sweating
• swelling of the face, throat, or tongue

• Redness, soreness, or itching of the skin
• sores, welts, blisters

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Belching
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• heartburn
• indigestion
• stomach discomfort or upset

• Diarrhea
• pain in the arms or legs

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Orencia during pregnancy. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972.

The data with Orencia use in pregnant women are insufficient to inform on drug-associated risk. In reproductive toxicology studies in rats and rabbits, no fetal malformations were observed with intravenous administration of Orencia 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 rats, Orencia altered immune function in female rats at 11 times the MRHD on an AUC basis.

Human Data

There are no adequate and well-controlled studies of Orencia use in pregnant women. The data with Orencia use in pregnant women are insufficient to inform on drug-associated risk.

Animal Data

Intravenous administration of abatacept during organogenesis to mice (10, 55, or 300 mg/kg/day), rats (10, 45, or 200 mg/kg/day), and rabbits (10, 45, or 200 mg/kg every 3 days) produced exposures in rats and rabbits that were approximately 29 times the MRHD on an AUC basis (at maternal doses of 200 mg/kg/day in rats and rabbits), and no embryotoxicity or fetal malformations were observed in any species.

In a study of pre- and postnatal development in rats (10, 45, or 200 mg/kg every 3 days from gestation day 6 through lactation day 21), alterations in immune function in female offspring, consisting of a 9-fold increase in T-cell-dependent antibody response relative to controls on postnatal day (PND) 56 and thyroiditis in a single female pup on PND 112, occurred at approximately 11 times the MRHD on an AUC basis (at a maternal dose of 200 mg/kg). No adverse effects were observed at approximately 3 times the MRHD (a maternal dose of 45 mg/kg). It is not known if immunologic perturbations in rats are relevant indicators of a risk for development of autoimmune diseases in humans exposed in utero to abatacept. Exposure to abatacept in the juvenile rat, which may be more representative of the fetal immune system state in the human, resulted in immune system abnormalities including inflammation of the thyroid and pancreas [see Nonclinical Toxicology (13.2)].

Lactation

There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Pediatric Use

In Study JIA-1, Orencia with intravenous administration was shown to reduce signs and symptoms of active polyarticular JIA in patients 6 to 17 years of age [see Clinical Studies (14.2)]. Orencia with intravenous administration has not been studied in patients younger than 6 years of age.

In Study JIA-2, the PK and safety of Orencia prefilled syringe for subcutaneous injection have been studied in patients 2 to 17 years of age. The efficacy of Orencia for subcutaneous injection in children 2 to 17 years of age is based on pharmacokinetic exposure and extrapolation of established efficacy of intravenous Orencia in polyarticular JIA patients and subcutaneous Orencia in patients with RA [see Clinical Pharmacology (12.3) and Clinical Studies (14.2)]. The safety and immunogenicity of Orencia for subcutaneous injection in children 2 to 17 years of age were assessed descriptively [see Adverse Reactions (6.4)]. Orencia may be used as monotherapy or concomitantly with methotrexate.

The safety and efficacy of Orencia ClickJect autoinjector for subcutaneous injection have not been studied in patients under 18 years of age.

Studies in juvenile rats exposed to Orencia prior to immune system maturity have shown immune system abnormalities including an increase in the incidence of infections leading to death as well as inflammation of the thyroid and pancreas [see Nonclinical Toxicology (13.2)]. Studies in adult mice and monkeys have not demonstrated similar findings. As the immune system of the rat is undeveloped in the first few weeks after birth, the relevance of these results to humans is unknown.

The safety and efficacy of Orencia in pediatric patients for uses other than juvenile idiopathic arthritis have not been established.

It is unknown if abatacept can cross the placenta into the fetus when the woman is treated with abatacept during pregnancy. Since abatacept is an immunomodulatory agent, the safety of administering live vaccines in infants exposed in utero to abatacept is unknown. Risk and benefits should be considered prior to vaccinating such infants.

Geriatric Use

A total of 323 patients 65 years of age and older, including 53 patients 75 years and older, received Orencia in clinical studies. No overall differences in safety or effectiveness were observed between these patients and younger patients, but these numbers are too low to rule out differences. The frequency of serious infection and malignancy among Orencia-treated patients over age 65 was higher than for those under age 65. Because there is a higher incidence of infections and malignancies in the elderly population in general, caution should be used when treating the elderly.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a mouse carcinogenicity study, weekly subcutaneous injections of 20, 65, or 200 mg/kg of abatacept administered for up to 84 weeks in males and 88 weeks in females were associated with increases in the incidence of malignant lymphomas (all doses) and mammary gland tumors (intermediate- and high-dose in females). The mice from this study were infected with murine leukemia virus and mouse mammary tumor virus. These viruses are associated with an increased incidence of lymphomas and mammary gland tumors, respectively, in immunosuppressed mice. The doses used in these studies produced exposures 0.8, 2.0, and 3.0 times higher, respectively, than the exposure associated with the maximum recommended human dose (MRHD) of 10 mg/kg based on AUC (area under the time-concentration curve). The relevance of these findings to the clinical use of Orencia is unknown.

In a one-year toxicity study in cynomolgus monkeys, abatacept was administered intravenously once weekly at doses up to 50 mg/kg (producing 9 times the MRHD exposure based on AUC). Abatacept was not associated with any significant drug-related toxicity. Reversible pharmacological effects consisted of minimal transient decreases in serum IgG and minimal to severe lymphoid depletion of germinal centers in the spleen and/or lymph nodes. No evidence of lymphomas or preneoplastic morphologic changes was observed, despite the presence of a virus (lymphocryptovirus) known to cause these lesions in immunosuppressed monkeys within the time frame of this study. The relevance of these findings to the clinical use of Orencia is unknown.

No mutagenic potential of abatacept was observed in the in vitro bacterial reverse mutation (Ames) or Chinese hamster ovary/hypoxanthine guanine phosphoribosyl-transferase (CHO/HGPRT) forward point mutation assays with or without metabolic activation, and no chromosomal aberrations were observed in human lymphocytes treated with abatacept with or without metabolic activation.

Abatacept had no adverse effects on male or female fertility in rats at doses up to 200 mg/kg every three days (11 times the MRHD exposure based on AUC).

Animal Toxicology and/or Pharmacology

A juvenile animal study was conducted in rats dosed with abatacept from 4 to 94 days of age in which an increase in the incidence of infections leading to death occurred at all doses compared with controls. Altered T-cell subsets including increased T-helper cells and reduced T-regulatory cells were observed. In addition, inhibition of T-cell-dependent antibody responses (TDAR) was observed. Upon following these animals into adulthood, lymphocytic inflammation of the thyroid and pancreatic islets was observed.

In studies of adult mice and monkeys, inhibition of TDAR was apparent. However, infection and mortality, altered T-helper cells, and inflammation of thyroid and pancreas were not observed.

Orencia® (oh-REN-see-ah)
(abatacept)
Prefilled Syringe with BD UltraSafe Passive™ Needle Guard

Step 1:  Preparing for an Orencia Injection

Step 2:   Examine the Prefilled Syringe

Step 3:  Check the Dose on the Prefilled Syringe

Step 4:  Choose and Prepare an Injection Site

Step 5:  Inject Your Dose of Orencia

Step 6:  After the Injection

Bristol-Myers Squibb Company
Princeton, NJ 08543 USA, U.S. License Number 1713

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Orencia is a registered trademark of Bristol-Myers Squibb Company.
BD UltraSafe Passive™ is a trademark of Becton, Dickinson and Company.

[Print Codes]
Revised March 2017

Before you start treatment with Orencia, your doctor may perform tests to make sure you do not have tuberculosis or other infections.

Orencia is injected under the skin, or into a vein through an IV. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of needles, IV tubing, and other items used.

Orencia is injected under the skin when given to a child between 2 and 6 years old.

Orencia must be given slowly when infected into a vein, and the IV infusion can take at least 30 minutes to complete.

This medicine is usually given every 1 to 4 weeks. Follow your doctor's instructions.

You may need to mix Orencia with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medication.

Do not shake the medication bottle or you may ruin the medicine. Prepare your dose only when you are ready to give an injection. Do not use if the medicine has changed colors or has particles in it. Call your pharmacist for new medicine.

Each single-use vial (bottle) or prefilled syringe of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

If you need surgery, tell the surgeon ahead of time that you are using Orencia.

If you have ever had hepatitis B, Orencia can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

This medicine can cause false results with certain blood glucose tests, showing high blood sugar readings. If you have diabetes, talk to your doctor about the best way to check your blood sugar while you are using Orencia.

Autoimmune disorders are often treated with a combination of different drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice.

Store Orencia in the refrigerator. Do not freeze. Keep the medicine in original carton to protect it from light. Do not use Orencia if the expiration date on the medicine label has passed.

If you need to transport the medicine, place the syringes in a cooler with ice packs.

Orencia that has been mixed with a diluent may be stored in a refrigerator or at room temperature and used within 24 hours.

Do not receive a "live" vaccine while using Orencia, and for at least 3 months after your treatment ends. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Common side effects of Orencia include: headache and nasopharyngitis. Other side effects include: dyspepsia and hypertension. See below for a comprehensive list of adverse effects.

Applies to abatacept: powder for solution, solution

Along with its needed effects, abatacept (the active ingredient contained in Orencia) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking abatacept:

• Back pain
• bladder pain
• bloody or cloudy urine
• body aches or pain
• chills
• cough
• cough producing mucus
• difficult or labored breathing
• difficult, burning, or painful urination
• dizziness
• ear congestion
• fever
• frequent urge to urinate
• headache
• loss of voice
• lower back or side pain
• nausea or vomiting
• noisy breathing
• pain or tenderness around the eyes and cheekbones
• sneezing
• sore throat
• stuffy or runny nose
• tightness of the chest
• troubled breathing
• unusual tiredness or weakness

• Blurred vision
• burning or stinging of the skin
• chest pain
• nervousness
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• pounding in the ears
• skin rash
• slow or fast heartbeat

• Confusion
• difficulty with swallowing
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• flushing
• hives or welts
• itching, pain, redness, swelling, tenderness, or warmth on the skin
• stomach pain or tenderness
• sweating
• swelling of the face, throat, or tongue

• Redness, soreness, or itching of the skin
• sores, welts, blisters

Some side effects of abatacept may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Belching
• bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• heartburn
• indigestion
• stomach discomfort or upset

• Diarrhea
• pain in the arms or legs