Flixabi - patient leaflet, side effects, dosage

1. What Flixabi is and what it is used for

Flixabi contains the active substance infliximab. Infliximab is a monoclonal antibody – a type of protein that attaches to a specific target in the body called TNF (tumour necrosis factor) alpha.

Flixabi 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.

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

• Crohn’s disease
• Ulcerative colitis.

Flixabi works by selectively attaching to TNF alpha and blocking its action. TNF alpha is involved in inflammatory processes of the body so 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 these medicines do not work well enough, you will be given Flixabi 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 these medicines do not work well enough, you will be given Flixabi 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 these medicines do not work well enough, you will be given Flixabi 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 these medicines or treatments do not work well enough, you will be given Flixabi 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 these medicines do not work well enough, you will be given Flixabi 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 these medicines do not work well enough, you will be given Flixabi 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.

2. What you need to know before Flixabi is given

You should not be given Flixabi if

• You are allergic to infliximab or any of the other ingredients of this medicine (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 use Flixabi if any of the above applies to you. If you are not sure, talk to your doctor before you are given Flixabi.

Warnings and precautions

Talk to your doctor before or during treatment with Flixabi if you have:

Had treatment with any medicine containing infliximab before

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

Infections

• Tell your doctor before you are given Flixabi if you have an infection even if it is a very minor one.
• Tell your doctor before you are given Flixabi if you have ever lived in or travelled to an area where infections called histoplasmosis, coccidioidomycosis, or blastomycosis are common. These infections are caused by specific types of fungi that can affect the lungs or other parts of your body.
• You may get infections more easily when you are being treated with Flixabi. If you are 65 or older, you have a greater risk.
• These infections may be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other organisms in the environment and sepsis that may be life-threatening.

Tell your doctor straight away if you get signs of infection during treatment with Flixabi. Signs include fever, cough, flu-like signs, feeling unwell, red or hot skin, wounds or dental problems. Your doctor may recommend temporarily stopping Flixabi.

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 Flixabi, even in patients who have already been treated with medicines for TB. Your doctor will record these tests on your patient reminder card.
• If your doctor feels that you are at risk for TB, you may be treated with medicines for TB before you are given Flixabi.

Tell your doctor straight away if you get signs of TB during treatment with Flixabi. Signs include persistent cough, weight loss, feeling tired, fever, night sweats.

Hepatitis B virus

• Tell your doctor before you are given Flixabi if you are a carrier of hepatitis B or have ever had it.
• Tell your doctor if you think you might be at risk of contracting hepatitis B.
• Your doctor should test you for hepatitis B virus.
• Treatment with TNF blockers such as Flixabi 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.

Tell your doctor straight away if you get new or worsening signs of heart failure during treatment with Flixabi. Signs include shortness of breath or swelling of your feet.

Cancer and lymphoma

• Tell your doctor before you are given Flixabi if you have or have ever had lymphoma (a type of blood cancer) or any other cancer.
• Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at higher risk of developing lymphoma.
• Children and adults taking Flixabi may have an increased risk of developing lymphoma or another cancer.
• Some patients who have received TNF-blockers, including Flixabi have developed a rare type of cancer called hepatosplenic T-cell lymphoma. Of these patients, most were teenage boys or young men and most had either Crohn’s disease or ulcerative colitis. This type of cancer has usually resulted in death. Almost all patients had also received medicines containing azathioprine or 6-mercaptopurine in addition to TNF-blockers.
• Some patients treated with infliximab have developed certain kinds of skin cancer. If there are any changes in your skin or growths on the skin during or after therapy, tell your doctor.
• Some women being treated for rheumatoid arthritis with infliximab have developed cervical cancer. For women taking infliximab including those over 60 years of age, your doctor may recommend regular screening for cervical cancer.

Lung disease or heavy smoking

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

Vaccinations

• Talk to your doctor if you recently have had or are due to have a vaccine.
• You should receive recommended vaccinations before starting Flixabi treatment. You may receive

some vaccines during treatment with Flixabi but you should not receive live vaccines (vaccines that contain a living but weakened infectious agent) while using Flixabi because they may cause infections.

• If you received Flixabi while you were pregnant, your baby may also be at higher risk for getting an infection with live vaccines for up to six months after birth. It is important that you tell your baby's doctors and other health care professionals about your Flixabi use so they can decide when your baby should receive any vaccine, including live vaccines such as BCG (used to prevent tuberculosis).
• If you are breast-feeding, it is important that you tell your baby’s doctors and other healthcare professionals about your Flixabi use before your baby is given any vaccine. For more information see section on Pregnancy and breast feeding.

Therapeutic infectious agents

• Talk to your doctor if you have recently received or are scheduled to receive treatment with a therapeutic infectious agent (such as BCG instillation used for the treatment of cancer).

Operations or dental procedures

• Tell your doctor if you are going to have any operations or dental procedures.
• Tell your surgeon or dentist that you are having treatment with Flixabi by showing them your patient reminder card.

Liver problems

• Some patients receiving infliximab have developed serious liver problems.

Tell your doctor straight away if you get symptoms of liver problems during treatment with Flixabi. Signs include yellowing of the skin and eyes, dark-brown coloured urine, pain or swelling in the upper right side of the stomach area, joint pain, skin rashes, or fever.

Low blood counts

• In some patients receiving infliximab, the body may not make enough of the blood cells that help fight infections or help stop bleeding.

Tell your doctor straight away if you get symptoms of low blood counts during treatment with Flixabi. Signs include persistent fever, bleeding or bruising more easily, small red or purple spots caused by bleeding under the skin, or looking pale.

Immune system disorder

• Some patients receiving infliximab have developed symptoms of an immune system disorder called lupus.

Tell your doctor straight away if you develop symptoms of lupus during treatment with Flixabi. Signs include joint pain or a rash on cheeks or arms that is sensitive to the sun.

Children and adolescents

The information above also applies to children and adolescents. In addition:

• Some children and teenage patients who have received TNF-blockers such as Flixabi have developed

cancers, including unusual types, which sometimes resulted in death.

• More children taking Flixabi developed infections as compared to adults.
• Children should receive recommended vaccinations before starting Flixabi treatment.

Children may receive some vaccines during treatment with Flixabi but should not receive live vaccines while using Flixabi.

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

Other medicines and Flixabi

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

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

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

While using Flixabi you should not receive live vaccines (e.g. BCG vaccine). If you were using Flixabi during pregnancy or if you are receiving Flixabi while breast-feeding, tell your baby’s doctor and other healthcare professionals caring for your baby about your Flixabi use before the baby receives any vaccines.

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

Pregnancy, breast-feeding and fertility

• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. Flixabi should only be used during pregnancy or while breast-feeding if your doctor feels it is necessary for you.
• You should avoid getting pregnant when you are being treated with Flixabi and for 6 months after you stop being treated with it. Discuss the use of contraception during this time with your doctor.
• If you received Flixabi 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 healthcare professionals about your Flixabi use before your baby is given any vaccine. If you received Flixabi while pregnant, giving BCG vaccine (used to prevent tuberculosis) to your baby within 6 months after birth may result in infection with serious complications, including death. Live vaccines such as BCG should not be given to your baby within 6 months after birth. For more information see section on vaccination.
• If you are breast-feeding, it is important that you tell your baby’s doctors and other healthcare professionals about your Flixabi use before your baby is given any vaccine.
• Severely decreased numbers of white blood cells have been reported in infants born to women treated with Flixabi during pregnancy. If your baby has continual fevers or infections, contact your baby’s doctor immediately.

Driving and using machines

Flixabi has minor influence on the ability to drive and use machines, e.g. dizziness, vertigo.

Flixabi contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. However, before Flixabi is given to you, it is mixed with a solution that contains sodium. Talk to your doctor if you are on a low salt diet.

• 1. How Flixabi will be given

Rheumatoid arthritis

The usual dose is 3 mg for every kg of body weight.

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.

How Flixabi is given

• Flixabi will be given to you by your doctor or nurse.
• Your doctor or nurse will prepare the medicine for infusion.
• The medicine will be given as an infusion (drip) (over 2 hours) into one of your veins, usually in your arm. After the third treatment, your doctor may decide to give your dose of Flixabi over 1 hour.
• You will be monitored while you are given Flixabi and also for 1 to 2 hours afterwards.

How much Flixabi is given

• The doctor will decide your dose and how often you will be given Flixabi. This will depend on your disease, weight and how well you respond to Flixabi.
• The table below shows how often you will usually have this medicine after your first dose.

Use in children and adolescents

Flixabi should only be used in children and adolescents if they are being treated for Crohn’s disease or ulcerative colitis. These children must be 6 years of age or older.

If you are given too much Flixabi

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 Flixabi.

If you forget or miss your Flixabi infusion

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

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

2. Possible side effects

Like all medicines, this medicine 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 Flixabi 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. Some of these reactions may be serious or life-threatening. An allergic reaction could happen within 2 hours of your injection or later. More signs of allergic side effects 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 chest discomfort or pain, arm pain, stomach pain, shortness of breath, anxiety, lightheadedness, dizziness, fainting, sweating, nausea (feeling sick), vomiting, fluttering or pounding in your chest, a fast or a slow heartbeat, and swelling of your feet.
• Signs of infection (including TB) such as fever, feeling tired, cough which may be persistent, shortness of breath, flu-like symptoms, weight loss, night sweats, diarrhoea, wounds, collection of pus in the gut or around the anus (abscess), dental problems or burning sensation when urinating.
• Possible signs of cancer including but not limited to swelling of lymph nodes, weight loss, fever, unusual skin nodules, changes in moles or skin colouring, or unusual vaginal bleeding.
• 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 signs of a stroke (sudden

numbness or weakness of your face, arm or leg, especially on one side of your body; sudden confusion, trouble speaking or understanding; trouble seeing in one or both eyes, trouble walking, dizziness, loss of balance or coordination or a severe headache), fits, tingling/numbness in any part of your body, or weakness in arms or legs, changes in eyesight such as double vision or other eye problems.

• Signs of a liver problem (including hepatitis B infection when you have had hepatitis B in the past) such as yellowing of the skin or eyes, dark-brown coloured urine, pain or swelling in the upper right side of the stomach area, joint pain, skin rashes, or fever.
• Signs of an immune system disorder such as joint pain or a rash on cheeks or arms that is sensitive to the sun (lupus) or cough, shortness of breath, fever or skin rash (sarcoidosis).
• Signs of low blood counts such as persistent fever, bleeding or bruising more easily, small red or purple spots caused by bleeding under the skin, or looking pale.
• Signs of serious skin problems such as reddish-target-like spots or circular patches often with central blisters on the trunk, large areas of peeling and shedding (exfoliating) skin, ulcers of mouth, throat, nose, genitals and eyes or small pus-filled bumps that can spread over the body. These skin reactions can be accompanied by fever.

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

The following side effects have been observed with infliximab:

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

• Stomach pain, feeling sick
• Viral infections such as herpes or flu
• Upper respiratory infections such as sinusitis
• Headache
• Side effect due to an infusion
• Pain.

Common (may affect up to 1 in 10 people)

• Changes in how your liver works, increase in liver enzymes (shown in blood tests)
• Lung or chest infections such as bronchitis or pneumonia
• Difficult or painful breathing, chest pain
• Bleeding in the stomach or intestines, diarrhoea, indigestion, heartburn, constipation
• Nettle-type rash (hives), itchy rash or dry skin
• Balance problems or feeling dizzy
• Fever, increased sweating
• Circulation problems such as low or high blood pressure
• Bruising, hot flush or nosebleed, warm, red skin (flushing)
• Feeling tired or weak
• Bacterial infections such as blood poisoning, abscess or infection of the skin (cellulitis)
• Infection of the skin due to a fungus
• Blood problems such as anaemia or low white blood cell count
• Swollen lymph nodes
• Depression, problems sleeping
• Eye problems, including red eyes and infections
• Fast heart beat (tachycardia) or palpitations
• Pain in the joints, muscles or back
• Urinary tract infection
• Psoriasis, skin problems such as eczema and hair loss
• Reactions at the injection site such as pain, swelling, redness or itching
• Chills, a build up of fluid under the skin causing swelling
• Feeling numb or having a tingling feeling.

Uncommon (may affect up to 1 in 100 people)

• Shortage of blood supply, swelling of a vein
• Collection of blood outside the blood vessels (haematoma) or bruising
• Skin problems such as blistering, warts, abnormal skin colouration or pigmentation, or swollen lips, or thickening of the skin, or red, scaly and flaky skin
• Severe allergic reactions (e.g. anaphylaxis), an immune system disorder called lupus, allergic reactions to foreign proteins
• Wounds taking longer to heal
• Swelling of the liver (hepatitis) or gall bladder, liver damage
• Feeling forgetful, irritable, confused, nervous
• Eye problems including blurred or reduced vision, puffy eyes or sties
• New or worsening heart failure, slow heart rate
• Fainting
• Convulsions, nerve problems
• A hole in the bowel or blockage of the intestine, stomach pain or cramps
• Swelling of your pancreas (pancreatitis)
• Fungal infections such as yeast infection or fungal infection of the nails
• Lung problems (such as oedema)
• Fluid around the lungs (pleural effusion)
• Narrowed airway in the lungs, causing difficulty breathing
• Inflamed lining of the lung, causing sharp chest pains that feel worse with breathing (pleurisy)
• Tuberculosis
• Kidney infections
• Low platelet count, too many white blood cells
• Infections of the vagina
• Blood test result showing ‘antibodies’ against your own body
• Changes in cholesterol and fat levels in the blood.

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

• A type of blood cancer (lymphoma)
• Your blood not supplying enough oxygen to your body, circulation problems such as narrowing of a blood vessel
• Inflammation of the lining of the brain (meningitis)
• Infections due to a weakened immune system
• Hepatitis B infection when you have had hepatitis B in the past
• Inflamed liver caused by a problem with the immune system (autoimmune hepatitis)
• Liver problem that causes yellowing of the skin or eyes (jaundice)
• Abnormal tissue swelling or growth
• Severe allergic reaction that may cause loss of consciousness and could be life-threatening (anaphylactic shoc­k)
• Swelling of small blood vessels (vasculitis)
• Immune disorders that could affect the lungs, skin and lymph nodes (such as sarcoidosis)
• Collections of immune cells resulting from an inflammatory response (granulomatous lesions)
• Lack of interest or emotion
• Serious skin problems such as toxic epidermal necrolysis, Stevens-Johnson Syndrome and acute generalised exanthematous pustulosis
• Other skin problems such as erythema multiforme, lichenoid reactions (itchy reddish-purple skin rash and/or threadlike white-grey lines on mucous membranes), blisters and peeling skin, or boils (furunculosis)
• Serious nervous system disorders such as transverse myelitis, multiple sclerosis-like disease, optic neuritis and Guillain-Barré syndrome
• Inflammation in the eye that may cause changes in the vision, including blindness
• Fluid in the lining of the heart (pericardial effusion)
• Serious lung problems (such as interstitial lung disease)
• Melanoma (a type of skin cancer)
• Cervical cancer
• Low blood counts, including a severely decreased number of white blood cells
• Small red or purple spots caused by bleeding under the skin
• Abnormal values of a blood protein called ‘complement factor’ which is part of the immune system.

Not known (frequency cannot be estimated from the available data)

• Cancer in children and adults
• A rare blood cancer affecting mostly teenage boys or young men (hepatosplenic T-cell lymphoma)
• Liver failure
• Merkel cell carcinoma (a type of skin cancer)
• Kaposi’s sarcoma, a rare cancer related to infection with human herpes virus 8. Kaposi’s sarcoma most commonly appears as purple lesions on the skin
• Worsening of a condition called dermatomyositis (seen as a skin rash accompanying muscle weakness)
• Heart attack
• Stroke
• Temporary loss of sight during or within 2 hours of infusion
• Infection due to a live vaccine because of a weakened immune system.

Additional side effects in children and adolescents

Children and adolescents who took infliximab for Crohn’s disease showed some differences in side effects compared with adults who took infliximab for Crohn's disease. The side effects that happened more in children were: low red blood cells (anaemia), blood in stool, low overall levels of white blood cells (leucopenia), redness or blushing (flushing), viral infections, low levels of white blood cells that fight infection (neutropenia), bone fracture, bacterial infection and allergic reactions of the breathing tract.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects 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.

3. How to store Flixabi

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

• 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 and the carton after “EXP”. The expiry date refers to the last day of that month.
• Store in a refrigerator (2 °C – 8 °C).
• This medicine can also be stored in the original carton outside of refrigerated storage up to a maximum of 25 °C for a single period of up to six months, but not beyond the original expiry date. In this situation, do not return to refrigerated storage again. Write the new expiry date on the carton including day/month/year.

Discard this medicine if not used by the new expiry date or the expiry date printed on the carton, whichever is earlier.

• It is recommended that when Flixabi 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 the refrigerator at 2 °C to 8 °C up to 34 days and for an additional 24 hours at 25 °C after removal from refrigeration.

• Do not use this medicine if it is discoloured or if there are particles present.

4. Contents of the pack and other information

What Flixabi 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 monohydrate and dibasic sodium phosphate heptahydrate.

What Flixabi looks like and contents of the pack

Flixabi is supplied as a glass vial containing a powder for concentrate for solution for infusion. The powder is white.

Flixabi is produced in packs of 1, 2, 3, 4, or 5 vial(s). Not all pack sizes may be marketed.

Marketing Authorisation Holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Manufacturer

Biogen Netherlands B.V.

Prins Mauritslaan 13, 1171 LP, Badhoevedorp Netherlands

Samsung Bioepis NL B.V. Olof Palmestraat 10

2616 LR Delft

The Netherlands

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

Belgie/Belgiqu­e/Belgien

Biogen Belgium NV/S.A

Tél/Tel: + 32 (0)2 808 5947

Efc^rapufl

Ewopharma AG Representative Office

Tea.: + 359 249 176 81

Česká republika

Biogen (Czech Republic) s.r.o.

Tel: + 420 228 884 152

Malta

Pharma.MT Ltd

Tel: + 356 27 78 15 79

Nederland

Biogen Netherlands B.V.

Tel: + 31 (0)20 808 02 70

Norge

Biogen Norway AS

Tlf: + 47 21 93 95 87

Österreich

Biogen Austria GmbH

Tel: + 43 (0)1 267 51 42

Polska

Biogen Poland Sp. z o.o.

Tel.: + 48 22 116 86 94

Portugal

Biogen Portugal Sociedade Farmacéutica,

Unipessoal, Lda

Tel: + 351 308 800 792

Romania

Ewopharma AG Representative Office

Tel: + 40 377 881 045

Slovenija

Biogen Pharma d.o.o.

Tel: + 386 (0)1 888 81 07

Slovenská republika

Biogen Slovakia s.r.o.

Tel: + 421 (0)2 333 257 10

Suomi/Finland

Biogen Finland Oy

Puh/Tel: + 358 (0)9 427 041 08

Sverige

Biogen Sweden AB

Tel: +46 (0)8 525 038 36

United Kingdom (Northern Ireland)

Biogen Idec (Ireland) Ltd.

Tel: +44 (0)20 360 886 22

This leaflet was last revised in.

Other sources of information

Detailed information on this medicine is available

.

The following information is intended for healthcare professionals only:

Patients treated with Flixabi should be given the patient reminder card.

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Instructions for use and handling - storage conditions

Store at 2 °C – 8 °C.

Flixabi may be stored at temperatures up to a maximum of 25 °C for a single period of up to 6 months, but not exceeding the original expiry date. The new expiry date must be written on the carton. Upon removal from refrigerated storage, Flixabi must not be returned to refrigerated storage.

Instructions for use and handling - reconstitution, dilution and administration

In order to improve the traceability of biological medicinal products, the tradename and batch number of the administered medicinal product should be clearly recorded.

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

• 2. Under aseptic conditions, reconstitute each Flixabi 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. 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 Flixabi solution dose to 250 mL with sodium chloride

9 mg/mL (0.9%) solution for infusion. Do not dilute the reconstituted Flixabi solution with any other diluent. The dilution 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 Flixabi. Slowly add the total volume of reconstituted Flixabi solution to the 250-mL infusion bottle or bag. Gently mix. For volumes greater than 250 mL, either use a larger infusion bag (e.g. 500 mL, 1,000 mL) or use multiple 250 mL infusion bags to ensure that the concentration of the infusion solution does not exceed 4 mg/mL. If stored refrigerated after reconstitution and dilution, the infusion solution must be allowed to equilibrate at room temperature to 25 °C for 3 hours prior to Step 4 (infusion). Storage beyond 24 hours at 2 °C to 8 °C applies to preparation of Flixabi in the infusion bag only.

• 4. Administer the infusion solution over a period of not less than the infusion time recommended. Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 1.2 micrometre 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. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless reconstitution/di­lution has been taken place in controlled and validated aseptic conditions. 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 Flixabi with other agents. Do not infuse Flixabi concomitantly in the same intravenous line with other agents.

• 6. Visually inspect Flixabi 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.