FLIXABI 100mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Flixabi 100mg powder for concentrate for solution for infusion

Infliximab

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

• Keep this leaflet, you may need to read it again.
• Your doctor will also give you a patient information card, which contains important safety information that you need to know before and during treatment with Flixabi.
• If you have any further questions, ask your doctor.

• If you experience side effects, consult your doctor, even if they are listed in this leaflet. See section 4.

Contents of the pack

1. What is Flixabi and what is it used for
2. What you need to know before you are given Flixabi
3. How Flixabi will be given to you
4. Possible side effects
5. Storing Flixabi
6. Contents of the pack and further information

1. What is Flixabi and what is it used for

Flixabi contains the active substance infliximab. Infliximab is a monoclonal antibody – a type of protein that binds to a specific target in the body called TNF (tumor 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 from 6 years of age for:

• Crohn's disease.
• Ulcerative colitis.

Flixabi works by selectively binding to TNF alpha and blocking its action. TNF alpha is involved in inflammatory processes in the body, so blocking it can 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 medicines. If these medicines do not work well enough, you will be given Flixabi in combination with another medicine called methotrexate to:

• Reduce the signs and symptoms of your disease.
• Slow down the damage to 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.
• Reduce the damage to 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 intestine. 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 intestine. 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 your active Crohn's disease.
• Reduce the number of abnormal connections (fistulas) between your intestine and your skin, which have not been controlled by other medicines or surgery.

2. What you need to know before you are given Flixabi

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 moderate or severe heart failure.

If any of the above applies to you, do not use Flixabi. If you are not sure, consult your doctor before you are given Flixabi.

Warnings and precautions

Consult your doctor before or during treatment with Flixabi if:

You have previously been treated with a medicine that contains infliximab

• Tell your doctor if you have been treated with medicines that contain infliximab in the past and are now starting a new treatment with Flixabi.

If you have interrupted treatment with infliximab for more than 16 weeks, there is a greater risk of allergic reactions when you start treatment again.

Infections

• Before you are given Flixabi, tell your doctor if you have an infection, even if it is a minor one.
• Before you are given Flixabi, tell your doctor if you have ever lived or traveled in 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 65 years old, you have a greater risk.
• These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other organisms in the environment, and sepsis, which can be life-threatening.

Tell 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 feeling of warmth on the skin, wounds, or dental problems. Your doctor may recommend temporarily stopping treatment with 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 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 been treated with medicines for TB. Your doctor will record 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.

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

Hepatitis B virus

• Before you are given Flixabi, tell your doctor if you are a carrier of hepatitis B or if you have had hepatitis B in the past.
• Tell your doctor if you think you may be at risk of getting hepatitis B.
• Your doctor should do tests for the hepatitis B virus.
• Treatment with TNF blockers, such as Flixabi, may cause reactivation of the hepatitis B virus in patients who are carriers of this virus, which in some cases can be life-threatening.

Heart problems

• Tell your doctor if you have any heart problems, such as mild heart failure.
• Your doctor will want to keep a close eye on your heart.

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

Cancer and lymphoma

• Before you are given Flixabi, tell your doctor if you have or have 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 have a higher risk of developing lymphoma.
• Children and adults treated with Flixabi may have a 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 hepatosplenic T-cell lymphoma. Most of these patients were adolescent or young adult males with Crohn's disease or ulcerative colitis, and most were taking azathioprine or 6-mercaptopurine in addition to a TNF blocker. This type of cancer is usually fatal.
• Some patients treated with infliximab have developed certain types of skin cancer. Tell 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, including those over 60 years old, may need regular cervical cancer screening.

Lung disease or heavy smoking

• Before you are given Flixabi, tell your doctor 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 treatment with Flixabi.

Nervous system disease

• Tell your doctor if you have or have had any problems that affect your nervous system before you are given Flixabi. This includes multiple sclerosis, Guillain-Barré syndrome, if you have had seizures or have been diagnosed with "optic neuritis".

Tell your doctor immediately if you notice symptoms of nervous system disease during treatment with Flixabi. The symptoms can be changes in 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 (fistulas) before you are given Flixabi.

Vaccines

• Consult your doctor if you have recently had or are scheduled to have a vaccine.
• Before you start treatment with Flixabi, you should receive all recommended vaccines. You can receive some vaccines during treatment with Flixabi, but you should not receive live vaccines (vaccines that contain a live, weakened infectious agent) while you are using Flixabi, because they may cause infections.
• If you received Flixabi while you were pregnant, your baby may also have a higher risk of getting an infection as a result of receiving a live vaccine during the first year of life. It is important that you inform your baby's doctors and other healthcare professionals about your treatment with Flixabi so that they can decide when your baby can be vaccinated, including live vaccines, such as the BCG vaccine (used to prevent tuberculosis).
• If you are breastfeeding, it is important that you inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. You should not give your baby live vaccines, such as the BCG vaccine, while you are breastfeeding, unless your baby's doctor recommends otherwise. For more information, see the section on pregnancy and breastfeeding.

Therapeutic infectious agents

• Tell your doctor if you have recently received or are scheduled to receive treatment with an infectious agent (such as BCG instillation used for cancer treatment).

Surgery or dental procedures

• Tell your doctor if you are going to have any surgery or dental procedure.
• Tell your surgeon or dentist that you are being treated with Flixabi, and show them your patient information card.

Liver problems

• Some patients who received infliximab have developed serious liver problems.

Tell your doctor immediately if you notice symptoms of liver problems during treatment with Flixabi. The symptoms can be yellowing of the skin and eyes, dark brown urine, pain or swelling in the upper right side of the stomach, pain in the joints, skin rash, or fever.

Low blood cell counts

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

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

Immune system disorder

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

Tell your doctor immediately if you develop symptoms of lupus during treatment with Flixabi. The symptoms can be joint pain or a rash on the cheeks or arms caused by sun sensitivity.

Children and adolescents

The above information also applies to children and adolescents. Additionally:

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

If you are not sure if any of the above applies to you, consult 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 with inflammatory diseases are already taking medicines to treat their condition. These medicines may cause side effects. Your doctor will advise you which other medicines you should continue to use while you are being treated with 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 at the same time.
• Orencia (which contains abatacept). Flixabi and Orencia should not be used at the same time.

You should not receive live vaccines (e.g., BCG vaccine against tuberculosis) while you are 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 receives any vaccine.

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

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, 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 thinks it is necessary for you.
• You should avoid becoming pregnant while you are being treated with Flixabi and for 6 months after treatment has finished. Discuss the use of contraceptive measures during this time with your doctor.
• If you received Flixabi during your pregnancy, your baby may have a higher risk of getting an infection.
• It is important that you inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. If you received Flixabi while you were pregnant, giving the BCG vaccine to your baby within 12 months after birth may cause infection with serious complications, including death. You should not give your baby live vaccines, such as the BCG vaccine, within 12 months after birth, unless your baby's doctor recommends otherwise. For more information, see the section on vaccines.
• If you are breastfeeding, it is important that you inform your baby's doctors and other healthcare professionals about your treatment with Flixabi before your baby is vaccinated. You should not give your baby live vaccines while you are breastfeeding, unless your baby's doctor recommends otherwise.
• In children born to women treated with Flixabi during pregnancy, a serious decrease in the number of white blood cells in the blood has been reported. If your baby has fevers or infections, contact your baby's doctor immediately.

Driving and using machines

Flixabi has a minor influence on the ability to drive and use machines; for example, dizziness and vertigo.

Flixabi contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) 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-salt diet.

Flixabi contains polisorbate 80

This medicine contains 0.5 mg of polisorbate 80 in each vial (20 ml vial) equivalent to 0.5 mg/10 ml once reconstituted with 10 ml of water for injections. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergy.

3. How Flixabi will be administered to you

Rheumatoid Arthritis

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

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

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

How Flixabi will be administered to you

• Flixabi will be administered to you by your doctor or nurse.
• Your doctor or nurse will prepare the medicine for infusion.
• The medicine will be administered 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 administer your dose of Flixabi over 1 hour.
• You will be monitored while you are being administered Flixabi and also for 1 to 2 hours afterwards.

How much Flixabi will be administered to you

• Your doctor will decide on your dose and how often you will be administered Flixabi. This will depend on your disease, weight, and how you respond to Flixabi.
• The table below shows how often you will usually be administered 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 administered too much Flixabi

Since this medicine is being administered by your doctor or nurse, it is unlikely that you will be administered too much Flixabi. The adverse effects of administering too much Flixabi are unknown.

If you miss or do not attend a Flixabi infusion

If you miss or do not attend a scheduled infusion, make an appointment as soon as possible.

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

4. 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 need treatment. Side effects can also occur after your treatment with Flixabi has finished.

Tell 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 in swallowing or breathing, skin rash, hives, swelling of your hands, feet, or ankles. Some of these reactions can be serious or potentially life-threatening. An allergic reaction can occur within 2 hours of your injection or later. More signs of allergic side effects can occur up to 12 days after your injection, such as muscle pain, fever, joint pain or jaw pain, sore throat, or headache.
• Signs of a heart problemsuch as chest pain or discomfort, arm pain, stomach pain, difficulty breathing, anxiety, dizziness, fainting, sweating, nausea (feeling sick), vomiting, palpitations or pounding in the chest, fast or slow heartbeat, and swelling of the feet.
• Signs of infection (including TB)such as fever, tiredness, persistent cough, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhea, wounds, accumulation of pus in the abdomen or around the anus (abscess), dental problems, or a burning sensation when urinating.
• Possible signs of cancerincluding, but not limited to, swelling of the lymph nodes, weight loss, fever, unusual skin nodules, changes in moles or skin color, or unusual vaginal bleeding.
• Signs of a lung problemsuch as coughing, difficulty breathing, or chest tightness.
• 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, difficulty speaking or understanding; difficulty seeing with one or both eyes, difficulty walking, dizziness, loss of balance or coordination, or a severe headache), seizures, numbness/tingling in any part of your body, or weakness in arms or legs, vision changes such as double vision or other eye problems.
• Signs of a liver problem(including hepatitis B infection, when you have had hepatitis B before) such as yellowing of your skin and eyes, dark brown urine, pain or swelling in the upper right side of your stomach, 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 coughing, 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 on your skin caused by bleeding under the skin, or paleness.

• Signs of serious skin problemssuch as red, circular, patchy rashes on your trunk, often with central blisters, large areas of peeling skin, ulcers in your mouth, throat, nose, genitals, and eyes, or small pus-filled bumps that can spread across your body. These skin reactions can be accompanied by fever.

Tell 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
• Infusion-related reaction
• Pain

Common (may affect up to 1 in 10 people)

• Changes in liver function, increased liver enzymes (shown in blood tests)
• Lung or chest infections, such as bronchitis or pneumonia
• Difficulty breathing or painful breathing, chest pain
• Bleeding in the stomach or intestines, diarrhea, indigestion, heartburn, constipation
• Hives (nettle rash), itchy skin rash, dry skin
• Balance or dizziness problems
• Fever, increased sweating
• Circulation problems such as low or high blood pressure
• Bruising, flushing, or nosebleeds, feeling hot or redness of the skin (flushing)
• Fungal skin infection
• Feeling tired or weak
• Bacterial infections such as septicemia, abscess, or skin infection (cellulitis)
• Fungal skin infection
• Blood problems such as anemia or low white blood cell count
• Swollen lymph nodes
• Depression, sleep problems
• Eye problems, including red eyes and infections
• Fast heartbeat (tachycardia) or palpitations
• Joint, muscle, or back pain
• Urinary tract infection
• Psoriasis, skin problems such as eczema, and hair loss
• Injection site reactions such as pain, swelling, redness, or itching
• Chills, fluid accumulation under the skin causing swelling
• Feeling numb or tingling

Uncommon (may affect up to 1 in 100 people)

• Lack of blood flow, swelling of a vein
• Accumulation of blood outside the blood vessels (hematoma) or bruising
• Skin problems such as blisters, warts, unusual skin color or pigmentation, or swollen lips, or thickening of the skin, or redness, scaly and peeling skin
• 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 vision or reduced vision, or swollen eyes or with styes
• Heart problems or worsening of existing heart problems, slow heartbeat
• Fainting
• Seizures, nerve problems
• Intestinal ulcers or obstruction, stomach pain or cramps
• Pancreas inflammation (pancreatitis)
• Fungal infections such as yeast infection or fungal infection of the nails
• Lung problems (such as edema)
• Fluid around the lungs (pleural effusion)
• Narrowing of the airways in the lungs, causing difficulty breathing
• Inflammation of the membrane that protects the lung, causing sharp chest pain that worsens with breathing (pleurisy)
• Tuberculosis
• Kidney infections
• Low platelet count, too many white blood cells in the blood
• Vaginal infections
• Blood test result showing "antibodies" against your own body
• Changes in cholesterol and fat levels in the blood
• Weight gain (for most patients, the weight gain was small).

Rare (may affect up to 1 in 1000 people)

• A type of blood cancer (lymphoma)
• Lack of blood flow, 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 before
• Liver inflammation caused by an immune system problem (autoimmune hepatitis)
• Liver problem that causes yellowing of the skin and eyes (jaundice)
• Swelling or abnormal growth of tissues
• Severe allergic reaction that can cause loss of consciousness and can 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)
• Accumulation of immune cells as a result of an inflammatory response (granulomatous lesions)
• Lack of interest or emotion
• Serious skin problems such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and acute generalized exanthematous pustulosis
• Other skin problems such as erythema multiforme, lichenoid reactions (itchy, reddish-purple rash and/or thick gray-white lines on the mucous membranes), blisters, and peeling skin, or boils (furunculosis)
• Serious nervous system problems such as transverse myelitis, multiple sclerosis-like disease, optic neuritis, and Guillain-Barré syndrome
• Inflammation in the eye that can cause changes in vision, including blindness
• Fluid around the heart (pericardial effusion)
• Serious lung problems (such as interstitial lung disease)
• Melanoma (a type of skin cancer)
• Cervical cancer
• Low blood cell counts, including a severe decrease in the number of white blood cells in the blood
• Small red or purple spots on the skin caused by bleeding under the skin
• Abnormal blood test results showing "complement factor" that is part of the immune system.

Frequency not known(cannot be estimated from the available data)

• Cancer in children and adults
• A rare type of blood cancer that mainly affects young adolescent 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 human herpesvirus 8 infection. Kaposi's sarcoma usually appears as purple skin lesions.
• Worsening of a disease called dermatomyositis (characterized by a skin rash accompanied by muscle weakness)
• Heart attack
• Stroke

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

• Infection due to a live vaccine because of a weakened immune system.
• Post-procedure problems (including infectious and non-infectious problems)

Other side effects in children and adolescents

Children and adolescents who were 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 often in children were: low red blood cell count (anemia), blood in stool, low total white blood cell count (leucopenia), facial redness or flushing (flushing), viral infections, low white blood cell count that fights infection (neutropenia), bone fracture, bacterial infection, and allergic reactions of the respiratory tract.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V.

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Flixabi

Flixabi will be stored by healthcare professionals in the hospital or clinical center. The storage details, if needed, 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 carton after EXP. The expiry date is the last day of the month shown.
• Store in a refrigerator (between 2°C and 8°C).
• This medicine can also be stored in the original carton outside the refrigerator at a maximum temperature of 25°C for a single period not exceeding 6 months, but not beyond the original expiry date. In this case, do not put it back in the refrigerator. Write the new expiry date on the carton with the day/month/year. Discard this medicine if it is not used before the new expiry date or the expiry date stated on the carton, whichever is earlier.
• It is recommended that when Flixabi is prepared for infusion, it should be used as soon as possible (within 3 hours). However, if the solution is prepared under sterile conditions, it can be stored in a 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 medicine if it has changed color or contains particles.

6. Container contents and additional information

Composition of Flixabi

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

Appearance of the product and container contents

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

Flixabi is available in packs of 1, 2, 3, 4 or 5 vials. Not all pack sizes may be marketed.

Marketing authorisation holder

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

Manufacturer

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 on this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of last revision of thisleaflet:05/2025

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu

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This information is intended only for healthcare professionals:

Patient information cards should be provided to patients treated with Flixabi.

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should 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 6 months, but not beyond the original expiry date. The new expiry date must be written on the carton. Once removed from refrigeration, Flixabi must 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 trade name and batch number of the administered product must be clearly recorded.

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

1. 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 the vial cap and clean the top with a cotton swab moistened with 70% alcohol. Insert the syringe needle into the vial through the centre of the rubber stopper and direct the water for injections towards 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. It is not unusual for foam to form 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 alteration or other foreign particles.

1. Dilute the total dose volume of reconstituted Flixabi solution to 250 ml with 9 mg/ml (0.9%) sodium chloride solution for infusion. Do not dilute the reconstituted Flixabi solution with any other diluent. The dilution can be performed by removing a volume of the 9 mg/ml (0.9%) sodium chloride solution for infusion from the 250 ml glass bottle or infusion bag equal to the volume of the reconstituted Flixabi. Slowly add the total volume of reconstituted Flixabi solution to the 250 ml glass bottle or infusion bag. Mix gently. For volumes greater than 250 ml, use a larger infusion bag (e.g. 500 ml, 1000 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, allow the infusion solution to reach room temperature (25°C) for 3 hours before step 4 (infusion). Storage beyond 24 hours at 2°C-8°C applies only to the preparation of Flixabi in the infusion bag.

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

1. No physical-chemical compatibility studies have been conducted to evaluate the co-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 alteration. Do not use if visible opaque particles, colour alteration or other foreign particles are observed.

1. Disposal of unused medicinal products and all materials that have come into contact with them should be carried out in accordance with local regulations.