Package Insert: Information for the User

Flixabi 100mg powder for concentrate for solution for infusion

infliximab

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• Your doctor will also give you a patient information leaflet, which contains important safety information you need to know before and during your treatment with Flixabi.
• If you have any questions, consult your doctor.

• If you experience any adverse effects, consult your doctor, even if they are not listed in this package insert. See section4.

Flixabi contains the active ingredient infliximab. Infliximab is amonoclonal antibody – atype of proteinthat binds to a specific target in the body called TNF (tumor necrosis factor) alpha.

Flixabi belongs to a group of medications called ‘TNF blockers’. It is used in adults for the following inflammatory diseases:

• Rheumatoid arthritis.
• Psoriatic arthritis.
• Ankylosing spondylitis (Bechterew's disease).
• Poriasis.

Flixabi is also used in adults and children aged 6years and older for:

• Crohn's disease.
• Ulcerative colitis.

Flixabi actsselectively binding to TNF alpha and blocking its action.TNF alphais involved in the body's inflammatory processes, so blocking itcan reduce 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 medications. If these medicationsdo not work well enough, you will be given Flixabi in combination with another medication called methotrexate to:

• Reduce the signs and symptoms of your disease.
• Delay damage to your joints.
• Improve your physical condition.

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 medications. If these medicationsdo not work well enough, you will be given Flixabi to:

• Reduce the signs and symptoms of your disease.
• Decrease damage to your joints.
• Improve your physical condition.

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 medications. If these medicationsdo not work well enough, you will be given Flixabi to:

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

Poriasis

Poriasis is an inflammatory disease of the skin. If you have plaque psoriasis, moderate to severe, you will first be given other medications or treatments, such as phototherapy. If these medications or treatmentsdo 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 intestine. If you have ulcerative colitis, you will first be given other medications. If these medicationsdo 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 intestine. If you have Crohn's disease, you will first be given other medications. Ifthese medications do not work well enough, you will be given Flixabi to:

• Treat active Crohn's disease.
• Reduce the number of abnormal channels (fistulas) between your intestine and your skin, which have not been controlled by other medications or surgery.

You should not be given Flixabi if

• You are allergic to infliximab or any of the other components of this medicine (listed in section6).
• You are allergic (hypersensitive) to proteins that come from mice.
• You have tuberculosis (TB) or another serious infection such as pneumonia or septicemia.
• You have moderate to severe heart failure.

If any of the above applies to you, do notuseFlixabi. If you are unsure, consult your doctor before you are given Flixabi.

Warnings and precautions

Consult your doctor before or during treatment with Flixabi if:

You have received treatment with a medicine that contains infliximab before

• Inform your doctor if you have received treatment with medicines that contain infliximab in the past and are now starting treatment with Flixabi again.

If you have stopped treatment with infliximab more than 16weeks ago, there is a higher risk of allergic reactions when you start treatment again.

Infections

• Inform your doctor before you are given Flixabi if you have an infection, even a mild one.
• Inform your doctor before you are given Flixabi if you have ever lived or traveled to an area where infections such as 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 be more likely to get infections when you are being treated with Flixabi. If you are over 65years old, you are at higher risk.
• These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other organisms in the environment, and septicemia, which can be potentially fatal.

Inform your doctor immediately if you notice signs of infection during treatment with Flixabi, such as fever, cough, flu-like symptoms, general feeling of being unwell, redness or warmth in the skin, wounds, or dental problems. Your doctor may recommend temporarily stopping treatment with Flixabi.

Tuberculosis (TB)

• It is very important to inform your doctor if you have ever had TB or have been in close contact with someone who has had or has TB.
• Your doctor will do a test 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 note these tests on your patient information card.
• If your doctor thinks you are at risk of TB, you may be treated with medicines for TB before you are given Flixabi.

Inform your doctor immediately if you notice signs of TB during treatment with Flixabi. The signs include persistent cough, weight loss, feeling tired, fever, night sweats.

Hepatitis B virus

• Inform your doctor before you are given Flixabi if you are a carrier of hepatitis Bor if you have had it before.
• Inform your doctor if you think you may be at risk of gettinghepatitisB.
• Your doctor should do tests for the hepatitis B virus.
• Treatment with TNF blockers, such as Flixabi, can cause reactivation of the hepatitis B virus in patients who are carriers of this virus, which in some cases can be potentially fatal.

Heart problems

• Inform your doctor if you have any heart problems, such as mild heart failure.
• Your doctor will closely monitor yourheart.

Inform your doctor immediately if you notice new or worsening heart problems during treatment with Flixabi. The signs include difficulty breathing or swelling of the feet.

Cancer and lymphoma

• Inform your doctor before you are given Flixabi if you have or have had any type of cancer, including lymphoma (a type of blood 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 treated with Flixabi may be at higher risk of developing lymphoma or other types of cancer.
• Some patients who have received TNF blockers, including Flixabi, have developed a rare type of cancer called T-cell lymphoma of the liver and spleen. Most of these patients were adolescent boys or young men and had Crohn's disease or ulcerative colitis. This type of cancer is usually fatal. Almost all patients had also received medicines with azathioprine or 6-mercaptopurine, in addition to TNF blockers.
• Some patients treated with infliximab have developed certain types of skin cancer. Inform your doctor if you notice any changes in your skin or lumps on your skin during or after treatment.
• Some women treated with infliximab for rheumatoid arthritis have developed cervical cancer. Women treated with infliximab, even those over 60 years old, may be advised to have regular cervical cancer checks.

Lung disease or heavy smokers

• Inform 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 heavy smokers may be at higher risk of developing cancer with treatment with Flixabi.

Neurological disorders

• Inform your doctor if you have or have had any neurological disorder before you are given Flixabi. This includes multiple sclerosis, Guillain-Barré syndrome, if you have seizures or have been diagnosed with “optic neuritis”.

Inform your doctor immediately if you notice symptoms of neurological disorder during treatment with Flixabi. The symptoms may include changes in vision, weakness in your arms or legs, numbness or tingling in any part of your body.

Abnormal skin openings

• Inform your doctor if you have any abnormal skin ulcers (fistulas) before you are given Flixabi.

Vaccinations

• Consult your doctor if you have recently had or are due to have a vaccination.
• Before starting treatment with Flixabi, you should receive the recommended vaccinations. You can receive some vaccinations during treatment with Flixabi, but you should not receive live vaccines (vaccines that contain a weakened live agent) while using Flixabi because they can cause infections.
• If you received Flixabi while pregnant, your baby may be at higher risk of getting an infection.
• It is essential to inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated, including live vaccines such as the BCG vaccine (used to prevent tuberculosis).
• If you are breastfeeding, it is essential to inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. Live vaccines should not be given to your baby while breastfeeding unless your baby's doctor recommends otherwise.

Therapeutic infectious agents

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

Surgeries or dental procedures

• Inform your doctor if you are due to have any surgery or dental procedure.
• Inform your surgeon or dentist that you are being treated with Flixabi by showing them your patient information card.

Liver problems

• Some patients who received infliximab developed severe liver problems.

Inform your doctor immediately if you notice symptoms of liver problems during treatment with Flixabi. The symptoms may include yellowing of the skin and eyes, dark brown urine, pain or swelling in the upper right abdomen, joint pain, skin rashes, or fever.

Low blood cell counts

• In some patients who receive infliximab, the body cannot produce enough blood cells that help fight infections or stop bleeding.

Inform your doctor immediately if you notice symptoms of low blood cell counts during treatment with Flixabi. The symptoms may include persistent fever, bleeding or bruising easily, small red or purple spots caused by bleeding under the skin, or paleness.

Immune system disorders

• Some patients who received infliximab developed symptoms of an immune system disorder called lupus.

Inform your doctor immediately if you develop symptoms of lupus during treatment with Flixabi. The symptoms may include joint pain or a rash on your cheeks or arms that is sensitive to sunlight.

Children and adolescents

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

• Some children and adolescents treated with TNF blockers, including Flixabi, have developed cancers, including rare types, which in some cases have been fatal.
• Children treated with Flixabi developed infections more frequently than adults.
• Children should receive the recommended vaccinations before starting treatment with Flixabi. Children can receive some vaccinations during treatment with Flixabi, but they should not receive live vaccines while using Flixabi.

If you are unsure whether anything above applies to you, consult your doctor before you are given Flixabi.

Other medicines and Flixabi

Inform your doctor if you are using, have used recently, or may need to use any other medicine.

Patients with inflammatory diseases are already taking medicines to treat their condition. These medicines can cause side effects. Your doctor will advise you on which other medicines you should continue to take while being treated with Flixabi.

In particular, inform 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.

You should not receive live vaccines (e.g., the BCG vaccine against tuberculosis) while using Flixabi. If you were using Flixabi during pregnancy, or if you are receiving Flixabi during breastfeeding, inform your baby's doctor and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. For more information, see the section on Pregnancy and breastfeeding.

If you are unsure whether anything above applies to you, consult your doctor or pharmacist before using Flixabi.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Flixabi should only be used during pregnancy or breastfeeding if your doctor considers it necessary for you.
• You should avoid becoming pregnant while being treated with Flixabi and for 6months after stopping treatment. Discuss using contraceptive measures during that time with your doctor.
• If you received Flixabi during pregnancy, your baby may be at higher risk of getting an infection.
• It is essential to inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. If you received Flixabi while pregnant, giving the BCG vaccine (used to prevent tuberculosis) to your baby within 12 months of birth may cause infection with serious complications, including death. Live vaccines, such as the BCG vaccine, should not be given to your baby within 12 months of birth unless your baby's doctor recommends otherwise. For more information, see the section on vaccinations.
• If you are breastfeeding, it is essential to inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. Live vaccines should not be given to your baby while breastfeeding unless your baby's doctor recommends otherwise.
• Children born to women treated with Flixabi during pregnancy have been reported to have severe low white blood cell counts. If your baby has persistent fever or infections, contact your baby's doctor immediately.

Driving and using machines

The influence of Flixabi on your ability to drive and use machines is small, for example, dizziness and vertigo.

Flixabi contains sodium

This medicine contains less than 1mmol of sodium (23mg) per dose; this is, essentially “sodium-free”. However, before you are given Flixabi, it is mixed with a solution that contains sodium. Consult your doctor if you are on a low-sodium diet.

Rheumatoid Arthritis

The usual dose is 3mg per kilogram of body weight.

Psoriatic Arthritis, Ankylosing Spondylitis (Bechterew's Disease), Psoriasis, Ulcerative Colitis, and Crohn's Disease

The usual dose is 5mg per kilogram of body weight.

How Flixabi will be administered

• Flixabi will be administered by your doctor or nurse.
• Your doctor or nurse will preparethe medicationfor infusion.
• The medicationwillbe administered as an infusion (drip)(for 2hours) in one of your veins, normally in your arm. After the third treatment, your doctor may decide to administer your dose ofFlixabi for 1hour.
• You will be monitored while they administer Flixabi and also during 1 to 2hours afterwards.

How much Flixabi will be administered

• Your doctor will decide your dose and how often Flixabi will be administered. This will depend on your disease, weight, and how you respond to Flixabi.
• The table below shows how often this medicationis normally administeredafter 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 6years of age or older.

If too much Flixabi is administered

As this medication is being administered by your doctor or nurse, it is unlikely that you will be given too much Flixabi. The adverse effects of an overdose of Flixabi are unknown.

If you forget or miss a Flixabi infusion

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

If you have any other questions about the use of this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Most side effects are mild to moderate. However, some patients may experience severe side effects that may require treatment. Side effects can also occur after your treatment with Flixabi has ended.

Inform your doctor immediately if you notice any of the following:

• Signs of an allergic reactionsuch as swelling of your face, lips, mouth, or throat, which may cause difficulty swallowing or breathing, skin rash, urticaria, swelling of your hands, feet, or ankles. Some of these reactions can be severe or potentially life-threatening. An allergic reaction can occur within 2hours of your injection or later. Additional signs of allergic reactions may occur up to 12days after your injection, such as muscle pain, fever, joint pain, or headache.
• Signs of a heart problemsuch as chest pain or discomfort, arm pain, stomach pain, difficulty breathing, anxiety, dizziness, lightheadedness, sweating, nausea (feeling sick), vomiting, palpitations, or rapid or slow heartbeat, and swelling of your feet.
• Signs of infection (including TB)such as fever, fatigue, persistent cough, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhea, wounds, accumulation of pus in your abdomen or around your anus (abscess), dental problems, or a burning sensation while urinating.
• Possible signs of cancerincluding, but not limited to, lymph node inflammation, weight loss, fever, rare skin nodules, changes in moles or skin color, or rare vaginal bleeding.
• Signs of a lung problemsuch as cough, difficulty breathing, or chest tightness.
• Signs of a nervous system problem (including eye problems)such as stroke symptoms (sudden numbness or weakness in your face, arm, or leg, especially on one side of your body; sudden confusion, difficulty speaking or understanding; difficulty seeing in one or both eyes, difficulty walking, dizziness, loss of balance or coordination, or severe headache), seizures, numbness or tingling in any part of your body, or weakness in your arms or legs, eye changes such as double vision or other eye problems.
• Signs of a liver problem(including hepatitis B infection, when you have had hepatitis B previously)such as yellow skin and eyes, dark brown urine, upper right abdominal pain or swelling, joint pain, skin rash, or fever.
• Signs of an immune system disordersuch as joint pain or a sun-sensitive rash on your cheeks or arms (lupus) or cough, difficulty breathing, fever, or skin rash (sarcoidosis).

• Signs of low blood cell countssuch as persistent fever, bleeding or bruising easily, small red or purple spots caused by bleeding under the skin, or paleness.

• Signs of severe skin problemssuch as circular, red patches with central blisters on your trunk, large areas of skin that are peeling and flaking, mouth, throat, nose, genital, or eye ulcers, or small, pus-filled bumps that can spread throughout your body. These skin reactions may be accompanied by fever.

Inform your doctor immediately 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, nausea
• Viral infections such as herpes or flu
• Upper respiratory tract infections such as sinusitis
• Headache
• Side effect due to infusion
• Pain

Common (may affect up to 1 in 10 people)

• Liver function changes, increased liver enzymes (shown in blood tests)
• Lung or chest infections, such as bronchitis or pneumonia
• Difficulty breathing or chest pain
• Stomach or intestinal bleeding, diarrhea, indigestion, heartburn, constipation
• Urticaria (hives), skin rash with itching or dry skin
• Balance problems or dizziness
• Fever, increased sweating
• Circulation problems such as low or high blood pressure
• Cardenals, shortness of breath, or nasal bleeding, heat, skin redness (rubefaction)
• Fungal skin infections
• Feeling tired or weak
• Bacterial infections such as septicemia, abscess, or skin infection (cellulitis)
• Fungal skin infections
• Blood problems such as anemia or low white blood cell count
• Lymph node inflammation
• Depression, difficulty sleeping
• Eye problems, including red eyes and infections
• Rapid heartbeat or palpitations
• Joint, muscle, or back pain
• Urinary tract infection
• Poriasis, skin problems such as eczema, and hair loss
• Reactions at the injection site such as pain, swelling, redness, or itching
• Chills, accumulation of fluid under the skin causing swelling
• Numbness or tingling

Uncommon (may affect up to 1 in 100 people)

• Poor blood circulation, swelling of a vein
• Blood accumulation outside of blood vessels (hematoma) or cardenals
• Skin problems such as blisters, warts, abnormal skin color or pigmentation, or swollen lips, or skin thickening, or redness, skin peeling and flaking
• Severe allergic reactions (e.g., anaphylaxis), immune system disorder called lupus, allergic reactions to foreign proteins
• Slow-healing wounds
• Liver inflammation (hepatitis) or bile duct inflammation, liver damage
• Feeling forgetful, irritable, confused, nervous
• Eye problems, including blurred or reduced vision, swollen or puffy eyes
• Heart problems or worsening of the same, decreased heartbeat
• Loss of consciousness
• Seizures, nervous system problems
• Intestinal ulcer or intestinal obstruction, stomach pain or cramps
• Pancreatitis (inflammation of the pancreas)
• Fungal infections such as yeast infection or fungal nail infection
• Lung problems (such as edema)
• Fluid around the lungs (pleural effusion)
• Wheezing in the lungs, causing difficulty breathing
• Pleurisy (inflammation of the membrane that protects the lung, causing severe chest pain that worsens with breathing)
• Tuberculosis
• Renal infections
• Low platelet count, too many white blood cells in the blood
• Vaginal infections
• Abnormal blood test results showing "antibodies" against your own body
• Changes in cholesterol and fat levels in the blood
• Weight gain (for most patients, weight gain was small).

Rare (may affect up to 1 in 1000 people)

• A type of blood cancer (lymphoma)
• Your blood does not provide enough oxygen to your body, circulation problems such as narrowing of a blood vessel
• Inflammation of the membranes that protect the brain (meningitis)
• Infections due to a weakened immune system
• Hepatitis B infection, when you have had hepatitis B previously
• Liver inflammation caused by an immune system problem (autoimmune hepatitis)
• Jaundice (yellow skin and eyes)
• Swelling or abnormal growth of tissues
• Severe allergic reaction that can cause loss of consciousness and may be life-threatening (anaphylactic shock)
• Inflammation of small blood vessels (vasculitis)
• Immune system disorders that can affect the lungs, skin, and lymph nodes (such as sarcoidosis)
• Accumulations of immune cells as a result of an inflammatory response (granulomatous lesions)
• Lack of interest or emotion
• Severe skin problems such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and generalized acute pustular psoriasis
• Other skin problems such as erythema multiforme, lichenoid reactions (red, itchy, and/or blistering skin rash and/or thick, white, or gray lines on mucous membranes), blisters, and skin peeling, or furunculosis (boils)
• Severe nervous system problems such as transverse myelitis, multiple sclerosis-like disease, optic neuritis, and Guillain-Barré syndrome
• Inflammation in the eye that can cause vision changes, including blindness
• Fluid in the membrane that protects the heart (pericardial effusion)
• Severe lung problems (such as interstitial lung disease)
• Melanoma (a type of skin cancer)
• Cervical cancer
• Low blood cell counts, including a severe decrease in white blood cell count
• Small red or purple spots caused by bleeding under the skin
• Abnormal levels of a blood protein called "complement factor" that is part of the immune system.

Frequency not known(cannot be estimated from available data)

• Cancer in children and adults
• A rare type of blood cancer that primarily affects adolescent boys or young men (hepatosplenic T-cell lymphoma)
• Liver failure
• Carcinoma of Merkel cells (a type of skin cancer)
• Kaposi's sarcoma, a rare cancer related to human herpesvirus 8 infection. Kaposi's sarcoma typically manifests as purple skin lesions.
• Worsening of a disease called dermatomyositis (manifesting as a skin rash accompanied by muscle weakness)
• Myocardial infarction
• Stroke

• Temporary loss of vision during or within 2hours of infusion

• Infection due to a live vaccine because of a weakened immune system.

Other side effects in children and adolescents

Children and adolescents treated with infliximab for Crohn's disease showed some differences in side effects compared to adults treated with infliximab for Crohn's disease. The side effects that occurred more frequently in children were: low red blood cell count (anemia), blood in stool, low total white blood cell count (leucopenia), facial redness or flushing (rubefaction), viral infections, low white blood cell count that fights infection (neutropenia), bone fractures, bacterial infections, and respiratory tract allergic reactions.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Flixabi will be stored by healthcare professionals in the hospital or clinical center. The storage details, if needed, are as follows:

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the label and in the box after CAD. The expiration date is the last day of the month indicated.
• Store in the refrigerator (between 2°C and 8°C).
• This medication can also be stored in the original box outside the refrigerator at a maximum temperature of 25°C for a single period not exceeding six months, but without exceeding the original expiration date.In this case, do not put it back in the refrigerator. Write the new expiration date on the box with day/month/year.
  Discard this medication if it has not been used before the new expiration date or the expiration date indicated on the box, whichever occurs first.
• It is recommended that when preparing Flixabi for infusion, it be 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 between 2°C and 8°C for up to 34 days and for an additional 24 hours at 25°C once removed from the refrigerator.
• Do not use this medication if there is a change in color or presence of particles.

Composition of Flixabi

• The active ingredient is infliximab. Each vial contains 100mg of infliximab. After preparation, each ml contains 10mg of infliximab
• The other components are sucrose, polisorbate 80 (E 433), sodium phosphate monobasic monohydrate, and sodium phosphate dibasic heptahydrate.

Appearance of the product and contents of the pack

Flixabi is presented in a glass vial containing a lyophilized powder for concentrate for solution for infusion. The powder is white.

Flixabi is available in packs of 1,2, 3, 4 or 5vials. Only some pack sizes may be marketed.

Marketing Authorization Holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

Responsible for manufacturing

Biogen Netherlands B.V.

Prins Mauritslaan 13,

1171 LP, Badhoevedorp

Netherlands

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country:

Last update of this leaflet: 09/2024

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu

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This information is intended for healthcare professionals only:

Patients treated with Flixabi should be given the patient information leaflet.

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

Instructions for use and handling – storage conditions

Store between 2°C and 8°C.

Flixabi can be stored at a maximum temperature of 25°C for a single period not exceeding 6months, but not exceeding the original expiry date. The new expiry date should be written on the box. Once removed from refrigeration, Flixabi should not be returned to the refrigerator.

Instructions for use and handling – reconstitution, dilution and administration

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

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

1. In aseptic conditions, reconstitute each vial of Flixabi with 10ml of water for injections, using a syringe equipped with a 21-gauge (0.8mm) or smaller needle. Remove the vial cap and clean the top with an alcohol-soaked cotton ball. Insert the syringe needle into the vial in the center of the rubber stopper and direct the water for injections towards the glass wall of the vial. Gently remove the solution by rotating the vial to dissolve the lyophilized powder. Avoid vigorous or prolonged agitation. DO NOT AGITATE. It is not uncommon for foam to form in the solution during reconstitution. Allow the reconstituted solution to stand for 5 minutes. Check that the solution is colourless to pale yellow and opalescent. The solution may contain a few fine translucent particles, as infliximab is a protein. Do not use if the solution contains opaque particles, colour change or other foreign particles.

1. Dilute the total dose volume of reconstituted Flixabi solution to 250ml with infusion solution 9mg/ml (0.9%) sodium chloride. Do not dilute the reconstituted Flixabi solution with any other diluent. The dilution can be performed by extracting 250ml from the glass vial or infusion bag. Add the total volume of reconstituted Flixabi solution slowly to the vial or infusion bag. Mix gently.For volumes greater than 250ml, use a larger infusion bag (e.g. 500ml, 1000ml) or use several 250ml infusion bags to ensure that the concentration of the infusion solution does not exceed 4mg/ml. If the reconstituted and diluted solution is stored refrigerated, it should be allowed to reach room temperature (25°C) for 3hours before the infusion step 4. The storage beyond 24hours at 2°C-8°C applies only to the Flixabi preparation in the infusion bag.

1. Administer the infusion solution over a period not less than the recommended infusion time. Use only a perfusion set with a low-protein affinity, non-pyrogenic and sterile (pore size 1.2micrometres or smaller) filter. Since it does not contain preservatives, it is recommended that the administration of the infusion solution be initiated as soon as possible and within 3hours of reconstitution and dilution. If not used immediately, the times and storage conditions before use are the responsibility of the user and should normally not be more than 24hours at 2°C-8°C, unless the reconstitution/dilution was carried out in controlled and validated aseptic conditions. Do not store any unused portion of infusion solution for re-use.

1. No compatibility studies have been performed to evaluate the concomitant administration of Flixabi with other agents. Do not infuse Flixabi concomitantly with other agents in the same intravenous line.

1. Before administration, visually inspect Flixabi for particles or colour change. Do not use if visible opaque particles, colour change or foreign particles are observed.

1. The disposal of unused medicinal product and all materials that have been in contact with it shall be in accordance with local requirements