ORENCIA 250 mg powder for concentrate for solution forinfusion

ORENCIA is an infusion treatment for adults with moderate to severe rheumatoid arthritis and for children and adolescents aged 6 to 17 years with polyarticular juvenile idiopathic arthritis. It is used in combination with a medicine called methotrexate. The active ingredient of ORENCIA, abatacept, is a protein produced in cell cultures.

Rheumatoid arthritis is a long-term progressive systemic disease that, if untreated, can lead to serious consequences, such as joint destruction, increased disability and impairment of daily activities. In people with rheumatoid arthritis the body's own immune system attacks normal body tissues, leading to pain and swelling of the joints. This can cause joint damage. ORENCIA lessens the immune system's attack on normal tissues by interfering with the immune cells (called T lymphocytes) that contribute to the development of rheumatoid arthritis.

ORENCIA is used to treat moderate to severe active rheumatoid arthritis when you do not respond well enough to treatment with other disease-modifying medicines or with another group of medicines called TNF blockers.

Polyarticular Juvenile Idiopathic Arthritis
Polyarticular juvenile idiopathic arthritis is a long-term inflammatory disease affecting one or more joints in children and adolescents.
ORENCIA is used after another group of medicines called TNF blockers. If you do not respond well enough to these medicines, you will be given ORENCIA with methotrexate to treat your polyarticular juvenile idiopathic arthritis.

ORENCIA is used to:

• slow down the damage to your joints
• improve your physical function
• improve signs and symptoms of polyarticular juvenile idiopathic arthritis

Do not use ORENCIA
If you are allergic (hypersensitive) to abatacept or any of the other ingredients.

If you have a severe or uncontrolled infection, therapy with ORENCIA must not be started. Having an infection could put you at risk of serious side effects from ORENCIA.

Take special care with ORENCIA
If you experience allergic reactions such as chest tightness, wheezing, severe dizziness or lightheadedness, swelling or skin rash tell your doctor immediately.
If you have any kind of infection, including long-term or localised infection, or often get infections. It is important you tell your doctor if you have symptoms of infection (e.g. fever, malaise, dental problems). ORENCIA also can lower your body's ability to fight infection and the treatment can make you more prone to getting infections or make any infection you have worse.
If you have had tuberculosis (TB) or have symptoms of tuberculosis (persistent cough, weight loss, listlessness, mild fever) tell your doctor. Before you use ORENCIA, your doctor will examine you for tuberculosis or do a skin test.
If you have viral hepatitis tell your doctor. Before you use ORENCIA, your doctor may examine you for hepatitis.
If you have cancer. Your doctor will have to decide if you can still be given ORENCIA. If you recently had a vaccination or are planning to have one. Some vaccines should not be given while receiving ORENCIA. Check with your doctor before you receive any vaccines. It is recommended that patients with polyarticular juvenile idiopathic arthritis, if possible, be brought up to date with all immunisations in agreement with current immunisation guidelines prior to starting ORENCIA therapy.
If you are using a blood glucose monitor to check your blood glucose levels. ORENCIA contains maltose, which is a type of sugar that can give falsely high blood glucose readings with certain types of blood glucose monitors. Your doctor may recommend a different method for monitoring your blood glucose levels.

ORENCIA and older people

ORENCIA can be used by people over 65 with no change in dose. Since the elderly are more susceptible to infections and cancer, ORENCIA should be used with caution in this patient population.

ORENCIA and children

ORENCIA has not been studied in patients under 6 years of age, therefore ORENCIA is not recommended in this patient population.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
ORENCIA is not to be used with biological medicines for rheumatoid arthritis including adalimumab, etanercept, and infliximab; there is insufficient evidence to recommend co-administration with anakinra and rituximab.
ORENCIA can be taken with other medicines commonly used in the treatment of rheumatoid arthritis, such as steroids or painkillers including non-steroidal anti-inflammatories such as ibuprofen or diclofenac.
Ask your doctor or pharmacist for advice before taking any other medicine while using ORENCIA.

Pregnancy and breast-feeding

The effects of ORENCIA in pregnancy are not known, so do not use ORENCIA if you are pregnant unless your doctor specifically recommends it. Pregnancy must be avoided while using ORENCIA. Your doctor will advise you on adequate contraceptive methods while using ORENCIA and up to 14 weeks after the last dose. If you become pregnant while using ORENCIA, tell your doctor.

It is not known whether abatacept, the active ingredient, passes into human milk. Y ou must stop breast-feeding if you are being treated with ORENCIA and for up to 14 weeks after the last dose.

Driving and using machines

If you are feeling tired or unwell after receiving ORENCIA, you should not drive or operate any machinery. It is not known if ORENCIA will affect the ability to drive or use machines.

Important information about some of the ingredients of ORENCIA
This medicine contains 1.5 mmol (or 34.5 mg) sodium per maximum dose of 4 vials (0.375 mmol or 8.625 mg sodium per vial). To be taken into consideration by patients on a controlled sodium diet.

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

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

Your weight Dose Vials Less than 60 kg 500 mg 2 60 kg - 100 kg 750 mg 3 More than 100 kg 1000 mg 4

For children and adolescents aged 6 to 17 years with polyarticular juvenile idiopathic arthritis who weigh less than 75 kg, the recommended dose of abatacept is 10 mg/kg. Children weighing 75 kg or more should be administered ORENCIA following the adult dosing regimen.

How ORENCIA is given to you

ORENCIA is given to you into a vein, usually in your arm, over a period of 30 minutes. This procedure is referred to as an infusion. Healthcare professionals will monitor you while you receive your ORENCIA infusion.

How often ORENCIA is given to you

ORENCIA should be given to you again, 2 and then 4 weeks after the first infusion. After that you will receive a dose every 4 weeks. Your doctor will advise you on the duration of treatment and what other medications you may continue to take while on ORENCIA.

If you use more ORENCIA than you should

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

If you forget to use ORENCIA

If you miss receiving ORENCIA when you are supposed to, ask your doctor when to schedule your next dose.

If you stop using ORENCIA

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

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, ORENCIA can cause side effects, although not everybody gets them. The most common side effects with ORENCIA are headache and nausea. Like all medicines that affect your immune system, ORENCIA can cause serious side effects, which may need treatment.

Possible serious side effects include serious infections, malignancies and allergic reactions.

Tell your doctor immediately if you notice any of the following:
Severe rash, hives or other signs of allergic reaction
Swollen face, hands, feet
Trouble breathing or swallowing

Tell your doctor as soon as possible if you notice any of the following:
Signs of infection such as fever, malaise, dental problems, burning sensation during urination, painful skin rash, painful skin blisters, coughing

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

The frequency of possible side effects listed below is defined using the following convention:

very common common uncommon rare very rare not known affects more than 1 user in 10 affects 1 to 10 users in 100 affects 1 to 10 users in 1,000 affects 1 to 10 users in 10,000 affects less than 1 user in 10,000 frequency cannot be estimated from the available data

Very commonside effects: headache.

Common side effects: infections of nose, throat and lungs, urinary infections, painful skin blisters (herpes), rhinitis, dizziness, high blood pressure, flushing, cough, nausea, diarrhoea, upset stomach, abdominal pain, rash, fatigue, weakness and abnormal liver function tests.

Uncommonside effects: tooth infection, infected skin ulcer, nail fungal infection, skin cancer, low blood platelet count, low blood cell counts, allergic reactions, anxiety, numbness, hives, eye inflammation, dry eye, reduced vision, palpitation, rapid heart rate, low heart rate, low blood pressure, hot flush, mouth sores, increased tendency to bruise, hair loss, dry skin, painful joints, pain in the extremities, flu-like illness, increased weight, infusion-related reactions, depression, absence of menstruation, migraine, kidney infection, psoriasis, difficulty in breathing and throat tightness.

Rare side effects: blood stream infection.

Your doctor may also do tests to examine your blood values.

Children and adolescents with polyarticular juvenile idiopathic arthritis

The most frequent side effects are listed below:

Very common side effects: headache, nausea.

Common side effects: diarrhoea, cough, infections of nose and throat, fever, upper abdominal pain.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use after the expiry date which is stated on the label and the carton after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C - 8°C).

Store in the original package in order to protect from light.

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

Do not use ORENCIA if you notice opaque particles, discolouration or other foreign particles present in the infusion solution.

What ORENCIA contains

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.

What ORENCIA looks like and contents of the pack

ORENCIA powder for concentrate for solution for infusion is a white to off-white powder that can appear solid or broken into pieces.
ORENCIA is available in packs of either 1, 2 or 3 vials and is supplied with respectively 1, 2 or 3 silicone-free syringes.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Bristol-Myers Squibb Pharma EEIG
Uxbridge Business Park
Sanderson Road
Uxbridge UB8 1DH
United Kingdom

Manufacturer:
Bristol-Myers Squibb S.R.L.
Contrada Fontana del Ceraso
I-03012 Anagni-Frosinone
Italy

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

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This leaflet was last approved in

The following information is intended for medical or healthcare professionals only

Reconstitution and dilution should be performed in accordance with good practices rules, particularly with respect to asepsis.

Dose selection: see section 3 ?How to use ORENCIA? of the Package Leaflet

Reconstitution of vials: under aseptic conditions, reconstitute each vial with 10 ml of water for injections, using the silicone-free disposable syringe provided with each vial and an 18-21 gauge needle. Remove the flip-top from the vial and wipe the top with an alcohol 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 a vacuum is not present. Remove the syringe and needle after 10 ml of water for injections have been injected into the vial. To minimise foam formation in solutions of ORENCIA the vial should be rotated with gentle swirling until the contents are completely dissolved. Do not shake. Do not use prolonged or vigorous agitation. Upon complete dissolution of the powder, the vial should be vented with a needle to dissipate any foam that may be present. After reconstitution the solution should be clear and colourless to pale yellow. Do not use if opaque particles, discolouration, or other foreign particles are present.

Preparation of infusion: immediately after reconstitution, dilute the product to 100 ml with sodium chloride 9 mg/ml (0.9%) solution for injection. From a 100 ml infusion bag or bottle, withdraw a volume of 0.9% sodium chloride 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. Gently mix. The final concentration of abatacept in the bag or bottle will depend upon the amount of drug added, but will be no more than 10 mg/ml.

Administration: when reconstitution and dilution are performed under aseptic conditions ORENCIA infusion solution can be used immediately or within 24 hours if stored refrigerated at 2°C to 8°C. However, for microbiological reasons, it is to be used immediately. Prior to administration, the ORENCIA solution should be inspected visually for particulate matter and discolouration. Discard the solution if any particulate matter or discolouration is observed. The entire, fully diluted ORENCIA solution should be administered over a period of 30 minutes and must be administered with an infusion set and a sterile, non-pyrogenic, low-protein-binding filter (pore size of 0.2 to 1.2 ?m). Do not store any unused portion of the infusion solution for reuse.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.