Remicade 100 mg powder for concentrate for solution forinfusion

Remicade contains the active substance called infliximab. Infliximab is a type of protein of human and mouse origin.

Remicade belongs to a group of medicines called ?TNF blockers?. It is used in adults for the following inflammatory diseases:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis (Bechterew?s disease)
• Psoriasis
• Ulcerative colitis

Remicade is also used in adults and children 6 years of age or older for:

• Crohn?s disease.

Remicade works by blocking the action of a protein called ?tumour necrosis factor alpha? (TNF ?). This protein is involved in inflammatory processes of the body and blocking it can reduce the inflammation in your body.

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease of the joints . If you have active rheumatoid arthritis you will first be given other medicines. If you do not respond well enough to these medicines, you will be given Remicade which you will take in combination with another medicine called methotrexate to:

• Reduce the signs and symptoms of your disease,
• Slow down the damage in your joints,
• Improve your physical function.

Psoriatic arthritis

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

• Reduce the signs and symptoms of your disease,
• Slow down the damage in your joints,
• Improve your physical function.

Ankylosing spondylitis (Bechterew?s disease)

Ankylosing spondylitis is an inflammatory disease of the spine. If you have ankylosing spondylitis you will first be given other medicines. If you do not respond well enough to these medicines, you will be given Remicade to:

• Reduce the signs and symptoms of your disease,
• Improve your physical function.

Psoriasis

Psoriasis is an inflammatory disease of the skin. If you have moderate to severe plaque psoriasis, you will first be given other medicines or treatments, such as phototherapy. If you do not respond well enough to these medicines or treatments, you will be given Remicade to reduce the signs and symptoms of your disease.

Ulcerative colitis

Ulcerative colitis is an inflammatory disease of the bowel. If you have ulcerative colitis you will first be given other medicines. If you do not respond well enough to these medicines, you will be given Remicade to treat your disease.

Crohn?s disease

Crohn?s disease is an inflammatory disease of the bowel. If you have Crohn?s disease you will first be given other medicines. If you do not respond well enough to these, you will be given Remicade to:

• Treat active Crohn?s disease,
• Reduce the number of abnormal openings (fistulae) between your bowel and your skin that have not been controlled by other medicines or surgery.

You should not be given Remicade if:

• You are allergic (hypersensitive) to infliximab (the active ingredient in Remicade) or to any of the other ingredients in Remicade (listed in section 6)
• You are allergic (hypersensitive) to proteins that come from mice
• You have tuberculosis (TB) or another serious infection such as pneumonia or sepsis
• You have heart failure that is moderate or severe.

Do not have Remicade if any of the above applies to you. If you are not sure, talk to your doctor before you are given Remicade.

Take special care with Remicade

Check with your doctor before you are given Remicade if you have:

Had treatment with Remicade before

• Tell your doctor if you have had treatment with Remicade in the past and are now starting Remicade treatment again. If you have had a break in your Remicade treatment of more than 16 weeks, there is a higher risk for allergic reactions when you start the treatment again.

Infections

• Tell your doctor if you have an infection even if it is a very minor one before you are given Remicade
• Tell your doctor if you have lived in or travelled to an area where infections called histoplasmosis, coccidioidomycosis, or blastomycosis are common before you are given Remicade. These infections are caused byspecific types of fungithat can affect the lungs or other parts of your body
• You may get infections more easily when you are being treated with Remicade. If you are 65 or older, you have a greater risk
• These infections may be serious and include tuberculosis, infections caused by viruses, fungi or bacteria, or other opportunistic infections and sepsis that may, in rare cases, be life-threatening. Tell your doctor straight away if you get signs of infection during treatment with Remicade. Signs include fever, cough, flu-like signs, feeling unwell, red or hot skin, wounds or dental problems. Your doctor may recommend temporary discontinuation of Remicade.

Tuberculosis (TB)

• It is very important that you tell your doctor if you have ever had TB or if you have been in close contact with someone who has had or has TB
• Your doctor will test you to see if you have TB. Cases of TB have been reported in patients treated with Remicade. Your doctor will record these tests on your Patient Alert Card
• If your doctor feels that you are at risk for TB, you may be treated with medicines for TB before you are given Remicade. Tell your doctor straight away if you get signs of TB during treatment with Remicade. Signs include persistent cough, weight loss, feeling tired, fever, night sweats.

Hepatitis B virus (HBV)

• Tell your doctor if you are a carrier or if you have or have had hepatitis B before you are given Remicade
• Tell your doctor if you think you might be at risk of contracting HBV
• Your doctor should test you for HBV
• Treatment with TNF blockers such as Remicade may result in reactivation of hepatitis B virus in patients who carry this virus, which can be life-threatening in some cases.

Heart problems

• Tell your doctor if you have any heart problems, such as mild heart failure
• Your doctor will want to closely monitor your heart function. Tell your doctor straight away if you get new or worsening signs of heart failure during treatment with Remicade. Signs include shortness of breath or swelling of your feet.

Cancer and lymphoma

• Tell your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer before you are given Remicade
• Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at higher than average risk of developing lymphoma
• Children and adults taking Remicade may have an increased risk of developing lymphoma or another cancer
• Some children and teenage patients who have received TNF-blockers such as Remicade have developed cancers, including unusual types, which sometimes resulted in death
• Some patients with Crohn's disease or ulcerative colitis who have received Remicade have developed a rare type of cancer called Hepatosplenic T-cell Lymphoma. Most of these patients were adolescent or young adult males. This type of cancer has usually resulted in death. All of these patients had also received drugs known as azathioprine or 6-mercaptopurine.

Lung disease or heavy smoking

• Tell your doctor if you have a lung disease called Chronic Obstructive Pulmonary Disease (COPD) or if you are a heavy smoker, before you are given Remicade
• Patients with COPD and patients who are heavy smokers may have a higher risk of developing cancer with Remicade treatment.

Nervous system disease

• Tell your doctor if you have or have ever had a problem that affects your nervous system before you are given Remicade. This includes multiple sclerosis, Guillain-Barre syndrome, if you have fits or have been diagnosed with ?optic neuritis?. Tell your doctor straight away if you get symptoms of a nerve disease during treatment with Remicade. Signs include changes in your vision, weakness in your arms or legs, numbness or tingling in any part of your body.

Abnormal skin openings

• Tell your doctor if you have any abnormal skin openings (fistulae) before you are given Remicade.

Vaccinations

• Talk to your doctor if you recently have had or are due to have a vaccine
• You should not receive certain vaccines while using Remicade
• Certain vaccinations may cause infections. If you received Remicade while you were pregnant, your baby may be at higher risk for getting such an infection for up to approximately six months after the last dose you received during pregnancy. It is important that you tell your baby's doctors and other health care professionals about your Remicade use so they can decide when your baby should receive any vaccine.

Operations or dental procedures

• Tell your doctor if you are going to have any operations or dental procedures
• Tell your surgeon or dentist performing the procedure that you are having treatment with Remicade by showing them your Patient Alert Card.

If you are not sure if any of the above apply to you, talk to your doctor before you are given Remicade.

Using other medicines
Patients who have inflammatory diseases already take medicines to treat their problem. These medicines may cause side effects. Your doctor will advise you what other medicines you must keep using while you are having Remicade.

Tell your doctor if you are using or have recently used any other medicines, including medicines obtained without a prescription, such as vitamins and herbal medicines.

In particular, tell your doctor if you are using any of the following medicines:

• Medicines that affect your immune system
• Kineret (anakinra). Remicade and Kineret should not be used together
• Orencia (abatacept). Remicade and Orencia should not be used together.

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Remicade.

Pregnancy and breast-feeding

• Talk to your doctor before you are given Remicade if you are pregnant or might become pregnant
• Remicade is not recommended for use during pregnancy
• You must avoid getting pregnant when you are being treated with Remicade and for 6 months after you stop being treated with it. Make sure you use contraception during this time
• Do not breast-feed when you are being treated with Remicade or for 6 months after your last treatment with Remicade
• If you received Remicade during your pregnancy, your baby may have a higher risk for getting an infection. It is important that you tell your baby?s doctors and other health care professionals about your Remicade use before the baby receives any vaccine (for more information see section on vaccination).

Driving and using machines
Remicade is not likely to affect your ability to drive or use tools or machines. If you feel tired or unwell after having Remicade, do not drive or use any tools or machines.

How Remicade is given

• Remicade will be given to you by your doctor or nurse, in a hospital or clinic
• Your doctor or nurse will prepare the Remicade solution for injection
• The Remicade solution will be slowly injected (over a 2 hour period) into one of your veins. This will usually be in your arm. This is called an ?intravenous infusion? or drip
• You will be monitored while you are given Remicade and also for 1 to 2 hours after.

How much Remicade is given

• The doctor will decide your dose (in mg) and how often you will be given Remicade. This will depend on your disease, weight and how well you respond to Remicade
• The table below shows how often you will usually have this medicine.

1st treatment 0 weeks 2nd treatment 2 weeks after your 1st treatment 3rd treatment 6 weeks after your 1st treatment Further treatments Every 6 to 8 weeks depending on your disease

Rheumatoid arthritis

The usual dose is 3 mg for every kg of body weight. After the third treatment, your doctor may decide to give you Remicade over a 1 hour period.

Psoriatic arthritis, ankylosing spondylitis (Bechterew?s disease), psoriasis, ulcerative colitis and Crohn's disease
The usual dose is 5 mg for every kg of body weight.

Use in children

Remicade should only be used in children if they are being treated for Crohn?s disease. These children must be 6 years of age or older.

If you are given too much Remicade

As this medicine is being given by your doctor or nurse, it is unlikely that you will be given too much. There are no known side effects of having too much of Remicade.

If you forget or miss your Remicade infusion

If you forget or miss an appointment to receive Remicade, make another appointment as soon as possible.

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

Like all medicines, Remicade can cause side effects, although not everybody gets them. Most side effects are mild to moderate. However some patients may experience serious side effects and may require treatment. Side effects may also occur after your treatment with Remicade has stopped.

Tell your doctor straight away if you notice any of the following:

• Signs of an allergic reaction such as swelling of your face, lips, mouth or throat which may cause difficulty in swallowing or breathing, skin rash, hives, swelling of the hands, feet or ankles. An allergic reaction could happen within 2 hours of your injection or later. More signs of an allergic reaction that may happen up to 12 days after your injection include pain in the muscles, fever, joint or jaw pain, sore throat or headache
• Signs of a heart problem such as shortness of breath, swelling of your feet or changes in your heart beat
• Signs of infection (including TB) such as fever, feeling tired, (persistent) cough, shortness of breath, flu-like symptoms, weight loss, night sweats, diarrhoea, wounds, dental problems or burning when urinating
• Signs of a lung problem such as coughing,breathing difficulties or tightness in the chest
• Signs of a nervous system problem (including eye problems) such as fits, tingling or numbness in any part of your body, weakness in arms or legs, changes in eyesight such as double vision or other eye problems
• Signs of a liver problem such as yellowing of the skin or eyes, dark-brown coloured urine or pain in the upper right side of the stomach area, fever
• Signs of an immune system disorder called lupus such as joint pain or a rash on cheeks or arms that is sensitive to the sun
• Signs of a low blood count such as persistent fever, bleeding or bruising more easily or looking pale.

Tell your doctor straight away if you notice any of the above.

Common side effects (affects 1 to 10 patients in 100)

• Increase in liver enzymes (shown in blood tests taken by your doctor)
• Allergic reactions to foreign proteins
• Lung or chest infections such as bronchitis or pneumonia
• Difficult or painful breathing, chest pain
• Stomach pain, diarrhoea, feeling sick or indigestion
• Nettle-type rash (hives), itchy rash or dry skin
• Viral infections such as herpes or flu
• Balance problems or feeling dizzy
• Fever, increased sweating
• Warm, red skin (flushing)
• Feeling tired or weak
• Sinus infections
• Headache.

Uncommon side effects (affects 1 to 10 patients in 1,000)

• Circulation problems such as low or high blood pressure, shortage of blood supply, swelling or narrowing of a vein, bruising, hot flush or nosebleed
• Skin problems such as blistering, boils, eczema, warts, abnormal skin colouration or pigmentation, hair loss or swollen lips
• Severe allergic reactions (e.g. anaphylaxis), an immune system disorder called lupus
• Reactions where you have had the injection such as pain, swelling, redness or itching
• Wounds taking longer to heal, chills, or a build up of fluid under the skin causing swelling
• Swelling of the gall bladder or changes in how your liver works (shown in blood tests)
• Depression, feeling forgetful, irritable, confused, nervous, lack of interest or emotion
• Eye problems including blurred or reduced vision, red or puffy eyes or sties
• Problems sleeping
• Bacterial infections such as blood poisoning, abscess or infection under the skin (cellulitis)
• Heart problems (such as worsening of existing heart failure)
• Nervous system disorders (multiple sclerosis-like disease)
• Stomach pain or cramps, heartburn, constipation
• Fungal infections such as yeast infection
• Lung problems (such as oedema)
• Pain in the joints, muscles or back
• Kidney or urinary tract infections
• Blood problems such as anaemia
• Infections of the vagina.

Rare side effects (affects 1 to 10 patients in 10,000)

• A type of blood cancer (lymphoma)
• Bleeding or a hole around the stomach area or blockage of the intestine
• Your blood not supplying enough oxygen to your body
• Inflammation of the lining of the brain (meningitis)
• Too much fluid around the lungs (pleural effusion)
• Abnormal tissue swelling or growth
• Swelling of the liver (hepatitis)
• Fast heart beat (tachycardia)
• Immune disorders that could affect the lungs, skin and lymph nodes (such as sarcoidosis).

Other side effects (the frequency is unknown)

• Cancer in children and adults
• A rare blood cancer affecting young people (hepatosplenic T-cell lymphoma)
• Psoriasis,serious skin problems such as toxic epidermal necrolysis, Stevens-Johnson Syndrome or erythema multiforme
• Serious nervous system disorders such as Guillain-Barré syndrome, optic neuritis or transverse myelitis
• A build up of fluid in the lining of the heart (pericardial effusion)
• Hepatitis B infection when you have had hepatitis B in the past
• Serious lung problems (such as interstitial lung disease)
• Infections due to a weakened immune system
• Swelling of small blood vessels (vasculitis)
• Swelling of your pancreas (pancreatitis)
• Infection with Salmonella bacteria
• Liver failure or liver damage.

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

Remicade will be stored by the health professionals at the hospital or clinic. The storage details should you need them are as follows:

• Keep out of the reach and sight of children
• Do not use Remicade after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month
• Store in a refrigerator (2°C to 8°C).
• It is recommended that when Remicade is prepared for infusion, it is used as soon as possible (within 3 hours). However, if the solution is prepared in germ-free conditions, it can be stored in a refrigerator at 2°C to 8°C for 24 hours

The solution should not be used if discoloured or if there are particles present.

What Remicade contains

• The active substance is infliximab. Each vial contains 100 mg of infliximab. After preparation each ml contains 10 mg of infliximab
• The other ingredients are sucrose, polysorbate 80, monobasic sodium phosphate and dibasic sodium phosphate.

What Remicade looks like and contents of the pack

Remicade is supplied as a glass vial containing a powder for concentrate for solution for infusion. The powder is a freeze-dried white pellet.
Remicade is produced in packs of 1, 2, 3, 4 or 5 vials. Not all pack sizes may be marketed.

Marketing Authorisation Holder

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

Manufacturer

Janssen Biologics B.V.
Einsteinweg 101
2333 CB Leiden
The Netherlands

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien Rue de StalleStallestraat 73 B-1180 BruxellesBrusselBrüssel TélTel 32-02 370 92 11 LuxembourgLuxemburg Rue de Stalle 73 B-1180 BruxellesBrüssel BelgiqueBelgien TélTel 32-02 370 92 11

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Deutschland Norg

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LT 08124 Vilnius
Tel. + 370 52 101 868

This leaflet was last approved in {MM/YYYY}.

THE FOLLOWING INFORMATION IS INTENDED FOR MEDICAL OR HEALTHCARE PROFESSIONALS ONLY:

Instructions for use and handling ? reconstitution, dilution and administration

1. Calculate the dose and the number of Remicade vials needed. Each Remicade vial contains 100 mg infliximab. Calculate the total volume of reconstituted Remicade solution required.

2. Under aseptic conditions, reconstitute each Remicade vial with 10 ml of water for injections, using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. Remove flip-top from the vial and wipe the top with a 70% 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 the vacuum is not present. Gently swirl the solution by rotating the vial to dissolve the lyophilised powder. Avoid prolonged or vigorous agitation. DO NOT SHAKE. Foaming of the solution on reconstitution is not unusual. Allow the reconstituted solution to stand for 5 minutes. Check that the solution is colourless to light yellow and opalescent. The solution may develop a few fine translucent particles, as infliximab is a protein. Do not use if opaque particles, discolouration, or other foreign particles are present.

3. Dilute the total volume of the reconstituted Remicade solution dose to 250 ml with sodium chloride 9 mg/ml (0.9%) solution for infusion. This can be accomplished by withdrawing a volume of the sodium chloride 9 mg/ml (0.9%) solution for infusion from the 250-ml glass bottle or infusion bag equal to the volume of reconstituted Remicade. Slowly add the total volume of reconstituted Remicade solution to the 250-ml infusion bottle or bag. Gently mix.

4. Administer the infusion solution over a period of not less than the infusion time recommended for the specific indication. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 1.2 micrometer or less). Since no preservative is present, it is recommended that the administration of the solution for infusion is to be started as soon as possible and within 3 hours of reconstitution and dilution. When reconstitution and dilution are performed under aseptic conditions, Remicade infusion solution can be used within 24 hours if stored at 2°C to 8°C. Do not store any unused portion of the infusion solution for reuse.

5. No physical biochemical compatibility studies have been conducted to evaluate the co-administration of Remicade with other agents. Do not infuse Remicade concomitantly in the same intravenous line with other agents.

6. Visually inspect Remicade for particulate matter or discolouration prior to administration. Do not use if visibly opaque particles, discolouration or foreign particles are observed.

7. Any unused product or waste material should be disposed of in accordance with local requirements.