ORENCIA 250 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

ORENCIA250mg powder for concentrate for solution for infusion

abatacept

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack:

1. What ORENCIA is and what it is used for
2. What you need to know before you use ORENCIA
3. How to use ORENCIA
4. Possible side effects
5. Storage of ORENCIA
6. Contents of the pack and other information

1. What ORENCIA is and what it is used for

ORENCIA contains the active substance abatacept, a protein that is produced in cell cultures. ORENCIA reduces the attack of the immune system on normal tissues by interfering with immune cells (called T lymphocytes) that contribute to the development of rheumatoid arthritis. ORENCIA selectively modulates the activation of T lymphocytes involved in the inflammatory response of the immune system.

ORENCIA is used to treat rheumatoid arthritis and psoriatic arthritis in adults and also polyarticular juvenile idiopathic arthritis in children from 6 years of age.

Rheumatoid Arthritis

Rheumatoid arthritis is a progressive, long-term systemic disease that, if left untreated, can have serious consequences, such as destruction of joints, increased disability, and inability to perform daily activities. In people with rheumatoid arthritis, the body's own immune system attacks normal tissues, producing pain and swelling in the joints. This can damage the joints. Rheumatoid arthritis (RA) affects each person differently. In most people, joint symptoms develop gradually over several years. However, in some patients, RA can progress rapidly, and in others, it can occur for a limited period and then go into remission. RA is usually a chronic (long-term) disease, which means that, even with treatment, you may still have symptoms, and RA may continue to damage your joints. With the best treatment plan for you, you may be able to slow down this disease process, which could help reduce long-term joint damage, as well as pain and fatigue, and improve your overall quality of life.

ORENCIA is used to treat moderate to severe active rheumatoid arthritis when you have not responded sufficiently to treatment with other disease-modifying medicines or with another group of medicines called "tumor necrosis factor (TNF) inhibitors". It is used in combination with a medicine called methotrexate.

ORENCIA may also be used with methotrexate to treat rheumatoid arthritis that is progressing and has high activity without prior treatment with methotrexate.

Psoriatic Arthritis

Psoriatic arthritis is an inflammatory disease of the joints, usually accompanied by psoriasis, an inflammatory disease of the skin. If you have active psoriatic arthritis, you will first be given other medicines. If you do not respond sufficiently well to these medicines, you may be given ORENCIA to:

• Reduce the signs and symptoms of your disease.
• Reduce damage to your bones and joints.
• Improve your physical function and ability to perform normal daily activities.

ORENCIA alone or in combination with methotrexate is used to treat psoriatic arthritis.

Polyarticular Juvenile Idiopathic Arthritis

Polyarticular juvenile idiopathic arthritis is a long-term inflammatory disease that affects one or more joints in children and adolescents.

ORENCIA powder for concentrate for solution for infusion is used in children and adolescents from 6 to 17 years of age when previous treatment with a disease-modifying medicine has not worked well or is not suitable for them. ORENCIA is usually used in combination with methotrexate, although ORENCIA may also be used alone in case of intolerance to methotrexate or if treatment with methotrexate is inadequate.

ORENCIA is used to:

• delay joint damage
• improve physical function
• improve other signs and symptoms of polyarticular juvenile idiopathic arthritis

2. What you need to know before you use ORENCIA

Do not use ORENCIA

• if you are allergicto abatacept or any of the other ingredients of this medicine (listed in section 6).
• if you have a severe or uncontrolled infection, do not start treatment with ORENCIA. Having an infection could put you at risk due to the side effects of ORENCIA.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse:

• if you experience allergic reactionssuch as chest tightness, asthma, severe dizziness or lightheadedness, swelling or skin rash tell your doctor immediately.
• if you, your partner, or your caregiver notice new onset or worsening of neurological symptoms, including general muscle weakness, vision problems, difficulty speaking, a change in the way you walkor problems with balance, changes in thinking, memory, and orientationleading to confusion and personality changes, contact your doctor immediatelybecause they may be symptoms of a rare, serious, and potentially life-threatening brain infection called progressive multifocal leukoencephalopathy (PML).
• if you have any type of infection, including prolonged or localized infection, or if you often get infections or if you have symptoms of having an infection (e.g., fever, malaise, dental problems), it is important that you inform your doctor. ORENCIA may decrease your body's ability to fight an infection, and treatment may make you more prone to getting infections or worsening any infection you have.
• if you have had tuberculosis (TB)or have symptoms of tuberculosis (persistent cough, weight loss, apathy, low-grade fever) tell your doctor. Before using ORENCIA, your doctor will perform a tuberculosis test or a skin test.
• if you have viral hepatitisinform your doctor. Before using ORENCIA, your doctor may perform a test for hepatitis.
• if you have cancer, your doctor will decide whether you can be given ORENCIA.
• if you have been vaccinated recentlyor are planning to be vaccinated, tell your doctor. Some vaccines should not be given while you are being treated with ORENCIA. Consult your doctor before you receive any vaccine.It is recommended that patients with polyarticular juvenile idiopathic arthritis update their vaccination schedule, if possible, according to current vaccination guidelines before starting treatment with ORENCIA. Certain vaccines may cause infections. If you are given ORENCIA during pregnancy, your baby may have a higher risk of getting such an infection during the approximately 14 weeks after the last dose you received during pregnancy. It is essential that you inform your baby's doctors and other healthcare professionals about the use of ORENCIA during pregnancy so they can decide when to give your baby any vaccine.
• if you use a blood glucose monitorto check your glucose levels. ORENCIA contains maltose, a type of sugar that can give falsely elevated blood glucose results with certain types of blood glucose monitors. Your doctor may recommend a different method for checking your glucose levels.

Your doctor may also perform blood tests to check your blood values.

Children and adolescents

ORENCIA powder for concentrate for solution for infusion has not been studied in children and adolescents under 6 years of age, so it is not recommended to use ORENCIA powder for concentrate for solution for infusion in this patient population.

ORENCIA solution for injection in a pre-filled syringe is available for subcutaneous administration in pediatric patients from 2 years of age.

Using ORENCIA with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

ORENCIA must not be usedwith biological medicines for rheumatoid arthritis, including TNF inhibitors such as adalimumab, etanercept, and infliximab; there is not enough evidence to recommend that it be given with anakinra and rituximab.

ORENCIA can be usedwith other medicines commonly used to treat rheumatoid arthritis, such as steroids or painkillers, including non-steroidal anti-inflammatory drugs like ibuprofen or diclofenac.

Ask your doctor or pharmacist for advice before taking any other medicine while using ORENCIA.

Pregnancy and breastfeeding

The effects of ORENCIA on pregnancy are not known, so you must not use ORENCIA if you are pregnant unless your doctor recommends it.

• if you are a woman who could become pregnant, you must use a reliable method of contraception (birth control) during treatment with ORENCIA and for 14 weeks after the last dose. Your doctor will advise you on suitable methods.
• if you become pregnant during treatment with ORENCIA, tell your doctor.

If you receive ORENCIA during pregnancy, your baby may have a higher risk of getting an infection. It is essential that you inform your baby's doctors and other healthcare professionals about the use of ORENCIA during pregnancy before any vaccine is given to your baby (for more information, see the section on vaccination).

It is not known whether ORENCIA passes into breast milk. You must stop breastfeedingif you are being treated with ORENCIA until 14 weeks after the last dose.

Driving and using machines

It is unlikely that the use of ORENCIA will affect your ability to drive, ride a bicycle, or use machines. However, if you feel tired or unwell after receiving ORENCIA, do not drive, ride a bicycle, or operate any machinery.

ORENCIA contains sodium

This medicine contains 34.5 mg of sodium (the main component of table salt/kitchen salt) in each maximum dose of 4 vials (8.625 mg of sodium per vial). This is equivalent to 1.7% of the maximum recommended daily intake of sodium for an adult.

3. How to use ORENCIA

ORENCIA will be given to you under the supervision of a specialist doctor.

Recommended dose in adults

The recommended dose of abatacept for adults with rheumatoid arthritis or psoriatic arthritis is based on your body weight:

Your doctor will tell you about the duration of treatment and what other medicines, including other disease-modifying medicines, you can continue to take while being treated with ORENCIA.

ORENCIA can be used in adults over 65 years of age without the need to change the dose.

Use in children and adolescents

For children and adolescents from 6 to 17 years of age with polyarticular juvenile idiopathic arthritis who weigh less than 75 kg, the recommended dose of intravenous abatacept is 10 mg/kg. For children who weigh 75 kg or more, ORENCIA powder for concentrate for solution for infusion should be administered following the adult dosing regimen.

How ORENCIA is given to you

ORENCIA is given into a vein, usually in the arm, over a period of 30 minutes. This procedure is called an infusion. Healthcare professionals will supervise you while you are receiving the ORENCIA infusion.

ORENCIA is presented as a powder for solution for infusion. This means that before ORENCIA is given to you, it must first be dissolved in water for injections, and then diluted with sodium chloride 9 mg/ml (0.9%) solution for injection.

How often ORENCIA is given to you

After the first infusion, ORENCIA should be given again at 2 and 4 weeks. After this, you will receive a dose every 4 weeks. Your doctor will tell you about the duration of treatment and what other medicines you can continue to take while being treated with ORENCIA.

If you are given too much ORENCIA

If this happens, your doctor will monitor you for any signs or symptoms of side effects and treat them if necessary.

If you miss a dose of ORENCIA

If you miss a dose of ORENCIA when it was due, ask your doctor when to schedule the next dose.

If you stop treatment with ORENCIA

The decision to stop treatment with ORENCIA should be discussed with your doctor.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The most common side effects that occur with ORENCIA are upper respiratory tract infections (including infections of the nose and throat), headache, and nausea. ORENCIA can cause serious side effects that may require treatment.

Serious side effectsinclude serious infections, malignant neoplasms (cancer), and allergic reactions, as listed below.

Tell your doctor immediatelyif you notice any of the following symptoms:

• severe rash, hives, or other symptoms of an allergic reaction
• face, hands, or feet swollen
• difficulty breathing or swallowing
• fever, persistent cough, weight loss, fatigue

Tell your doctor immediatelyif you notice any of the following:

• general malaise, dental problems, burning sensation when urinating, painful skin rash, painful blisters on the skin, cough

The symptoms described above may be signs of the side effects listed below, which have been observed with ORENCIA in clinical trials in adults:

Very common(may affect more than 1 in 10 people):

• upper respiratory tract infections (including infections of the nose, throat, and sinuses).

Common(may affect up to 1 in 10 people):

• lung infections, urinary tract infections, painful blisters on the skin (herpes), rhinitis, flu
• headache, dizziness
• high blood pressure
• cough
• abdominal pain, diarrhea, nausea, stomach upset, mouth ulcers, vomiting
• skin rash
• fatigue, weakness
• abnormal liver function tests

Uncommon(may affect up to 1 in 100 people):

• dental infection, fungal infection of the nails, muscle infection, infection of the bloodstream, accumulation of pus under the skin, kidney infection, ear infection
• low white blood cell count in the blood
• skin cancer, warts
• low platelet count in the blood
• allergic reactions
• depression, anxiety, sleep disturbance
• migraine
• numbness
• dry eyes, decreased vision
• eye inflammation
• palpitations, rapid heartbeat, slow heartbeat
• low blood pressure, hot flushes, inflammation of blood vessels, redness
• difficulty breathing, wheezing, shortness of breath, acute worsening of a lung disease called chronic obstructive pulmonary disease (COPD)
• throat tightness
• rhinitis
• increased tendency to bruise, dry skin, psoriasis, redness of the skin, excessive sweating, acne
• hair loss, itching, hives
• joint pain
• pain in the limbs
• absence of menstruation, heavy menstrual bleeding
• pseudogrip syndrome, weight gain, infusion-related reactions

Rare(may affect up to 1 in 1,000 people):

• tuberculosis
• inflammation of the uterus, fallopian tubes, and/or ovaries
• gastrointestinal infection
• leukemia, lung cancer

Children and adolescents with polyarticular juvenile idiopathic arthritis

The side effects in children and adolescents with polyarticular juvenile idiopathic arthritis are similar to those experienced in adults described above, with the following differences:

Common(may affect up to 1 in 10 people):

• upper respiratory tract infection (including infections of the nose, sinuses, and throat)
• fever

Uncommon(may affect up to 1 in 100 people):

• blood in urine
• ear infection

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of ORENCIA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after EXP and on the carton after CAD. The expiry date is the last day of the month stated.

Store in a refrigerator (between 2°C and 8°C).

Store in the original packaging to protect from light.

After reconstitution and dilution, the infusion solution is stable in the refrigerator for 24 hours, but for microbiological reasons, it should be used immediately.

Do not use this medicine if you notice opaque particles, color changes, or other foreign particles in the infusion solution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package contents and additional information

Composition of ORENCIA

• The active substance is abatacept. Each vial contains 250 mg of abatacept.
• After reconstitution, each ml contains 25 mg of abatacept.
• The other ingredients are maltose, sodium dihydrogen phosphate monohydrate, and sodium chloride (see section 2 "ORENCIA contains sodium").

Appearance and package contents of the product

ORENCIA powder for concentrate for solution for infusion is a white to off-white powder that may be compacted or fragmented.

ORENCIA is available in packs of 1 vial and 1 silicone-free syringe, and in multiple packs with 2 or 3 vials and 2 or 3 silicone-free syringes (2 or 3 packs of 1).

Only certain pack sizes may be marketed.

Marketing authorisation holder

Bristol-Myers Squibb Pharma EEIG

Plaza 254

Blanchardstown Corporate Park 2

Dublin 15, D15 T867

Ireland

Manufacturer

CATALENT ANAGNI S.R.L.

Loc. Fontana del Ceraso snc

Strada Provinciale 12 Casilina, 41

03012 Anagni (FR)

Italy

Swords Laboratories Unlimited Company t/a Bristol-Myers Squibb Cruiserath Biologics

Cruiserath Road, Mulhuddart

Dublin 15

Ireland

Date of last revision of this leaflet:

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

Reconstitution and dilution should be performed in accordance with good practice, particularly with regard to asepsis.

Dose selection:see section 3 of the Summary of Product Characteristics "How to use ORENCIA".

Reconstitution of the vials:under aseptic conditions, reconstitute each vial with 10 ml of water for injections, using the silicone-free disposable syringe provided with each vialand an 18-21 gauge needle. Remove the vial cap and clean the top with an alcohol-moistened swab. Insert the syringe needle into the vial through the centre of the rubber stopper and direct the stream of water for injections to the glass wall of the vial. Do not use the vial if there is no vacuum. Withdraw the syringe and needle after injecting 10 ml of water for injections into the vial. To minimize foam formation in ORENCIA solutions, the vial should be swirled with spiral movements until the contents are completely dissolved. Do not shake. Avoid prolonged or vigorous shaking. Once the powder is dissolved, air should be withdrawn from the vial with a needle to dispel any foam that may be present. After reconstitution, the solution should be clear and colourless to pale yellow. Do not use if opaque particles, colour changes, or other foreign particles are observed.

Preparation of the infusion:immediately after reconstitution, dilute the concentrate to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection. Withdraw from the 100 ml infusion bag or bottle a volume of sodium chloride 0.9% solution for injection equal to the volume of the reconstituted ORENCIA vials. Slowly add the reconstituted ORENCIA solution from each vial to the infusion bag or bottle using the same silicone-free disposable syringe provided with each vial. Mix carefully. The final concentration of abatacept in the bag or bottle will depend on the amount of active substance added, but will not exceed 10 mg/ml.

Administration:when reconstitution and dilution are performed under aseptic conditions, the ORENCIA infusion solution can be used immediately or within 24 hours if stored in a refrigerator between 2°C and 8°C. However, for microbiological reasons, it should be used immediately. Before administration, the ORENCIA solution should be visually inspected for particulate matter and colour changes. Discard the solution if particles or colour changes are observed. The entire ORENCIA solution should be administered within 30 minutes and using an infusion kit and a sterile, non-pyrogenic, low-protein-binding filter (pore size 0.2 to 1.2 μm). Do not store the unused portion of the infusion solution for reuse.

Other medicines:ORENCIA should not be mixed or administered simultaneously with other medicines in the same intravenous line. No physical or biochemical compatibility studies have been conducted to evaluate the administration of ORENCIA with other medicines.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.