Flixabi 100 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

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, as you may need to read it again.

• Your doctor will also give you a patient information card containing important safety information that you need to know before and during your treatment with Flixabi.

• If you have any questions, consult your doctor.

• If you experience any adverse reactions, talk to your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

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 binds specifically to a target in the body called tumour necrosis factor (TNF) alpha.

Flixabi belongs to a group of medicines known as TNF blockers. It is used in adults for the following inflammatory conditions:

• 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 by blocking it, Flixabi can reduce inflammation.

Rheumatoid arthritis

Rheumatoid arthritis is an inflammatory disease affecting the joints. If you have active rheumatoid arthritis, you will first be given other medicines. If these 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
• Delay joint damage
• Improve your physical function

Psoriatic arthritis

Psoriatic arthritis is an inflammatory joint disease, usually accompanied by psoriasis. If you have active psoriatic arthritis, you will first be given other medicines. If these do not work well enough, you will be given Flixabi to:

• Reduce the signs and symptoms of your disease
• Reduce joint damage
• 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 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 skin disease. If you have moderate to severe plaque psoriasis, you will first be given other medicines or treatments, such as phototherapy. If these 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 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 do not work well enough, you will be given Flixabi to:

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

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

Do not take Flixabi if

• You are allergic to infliximab or to any of the other ingredients of this medicine (listed in section 6).
• You are allergic (hypersensitive) to proteins derived from mice.
• You have tuberculosis (TB) or another serious infection such as pneumonia or sepsis.
• You have moderate or severe heart failure (impaired heart function).

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

Warnings and precautions

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

You have previously received treatment with a medicine containing infliximab

• Inform your doctor if you have previously received treatment with medicines containing infliximab and are now restarting treatment with Flixabi.

If you have interrupted treatment with infliximab for more than 16 weeks, there is an increased risk of allergic reactions when restarting treatment.

Infections

• Before you are given Flixabi, inform your doctor if you have an infection, even if it is very mild.
• Before you are given Flixabi, inform your doctor if you have ever lived in or traveled to areas 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 susceptible to infections while being treated with Flixabi. The risk is higher if you are over 65 years old.
• These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other environmental organisms, and sepsis, which can potentially be fatal.

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

Tuberculosis (TB)

• It is very important that you inform your doctor if you have ever had TB or have been in close contact with someone who has or had TB.
• Your doctor will perform a test to check whether you have TB. Cases of TB have been reported in patients treated with Flixabi, including in patients who have previously been treated with TB medications. Your doctor will record these test results on your patient information card.
• If your doctor considers you to be at risk of TB, you may be treated with TB medications before receiving Flixabi.

Contact your doctor immediately if you notice signs of TB during treatment with Flixabi. Symptoms include persistent cough, weight loss, fatigue, fever, and night sweats.

Hepatitis B virus

• Before you are given Flixabi, inform your doctor if you are a carrier of hepatitis B or have ever had it.
• Inform your doctor if you think you may be at risk of contracting hepatitis B.
• Your doctor must perform tests for the hepatitis B virus.
• Treatment with TNF blockers, such as Flixabi, may cause reactivation of the hepatitis B virus in 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 dysfunction (mild heart failure).
• Your doctor may want to closely monitor your heart.

Contact your doctor immediately if you notice new symptoms or worsening of heart dysfunction during treatment with Flixabi. Symptoms include difficulty breathing or swelling of the feet.

Cancer and lymphoma

• Before you are given Flixabi, inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer.
• Patients with long-standing, severe rheumatoid arthritis may have an increased risk of developing lymphoma.
• Children and adults treated with Flixabi may have an increased 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 boys or young men, and the majority had Crohn’s disease or ulcerative colitis. This type of cancer was usually fatal. Almost all patients had also received 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 changes in your skin or skin lumps during or after treatment.
• Some women receiving infliximab for rheumatoid arthritis have developed cervical cancer. Women treated with infliximab, even those over 60 years old, may be advised by their doctor to have regular cervical cancer screenings.

Lung disease or heavy smokers

• Before you are given Flixabi, inform 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 heavy smokers may have an increased risk of developing cancer with Flixabi treatment.

Nervous system disorders

• Inform your doctor if you have or have ever had a condition affecting your nervous system before being given Flixabi. This includes multiple sclerosis, Guillain-Barré syndrome, seizures, or a diagnosis of "optic neuritis."

Contact your doctor immediately if you notice symptoms of a nervous system disorder during treatment with Flixabi. Symptoms may include changes in vision, weakness in arms or legs, numbness, or tingling anywhere in your body.

Abnormal skin openings

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

Vaccines

• Consult your doctor if you have recently received or need to receive a vaccine.
• Before starting treatment with Flixabi, you should receive all recommended vaccines. You may receive some vaccines during treatment with Flixabi, but you must not receive live microbial vaccines (vaccines containing a live but weakened infectious agent) while using Flixabi, as they may cause infections.
• If you received Flixabi while pregnant, your baby may also have an increased risk of infection as a result of receiving a live microbial vaccine during the first year of life. It is important to inform your baby’s doctors and other healthcare professionals about your Flixabi treatment so they can determine when your baby can be vaccinated, including live microbial vaccines such as the BCG vaccine (used to prevent tuberculosis).
• If you are breastfeeding, it is important to inform your baby’s doctors and other healthcare professionals about your Flixabi treatment before your baby is vaccinated. See the section on pregnancy and breastfeeding for more information.

Therapeutic infectious agents

• Inform 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

• Inform your doctor if you are scheduled for any surgery or dental procedure.
• Inform 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.

Contact your doctor immediately if you notice symptoms of liver problems during treatment with Flixabi. Symptoms may include yellowing of the skin or eyes, dark brown urine, pain or swelling in the upper right part of the stomach, joint pain, skin rash, or fever.

Low blood cell counts

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

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

Immune system disorders

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

Contact your doctor immediately if you develop symptoms of lupus during treatment with Flixabi. Symptoms may include joint pain or a rash on the cheeks or arms after sun exposure.

Children and adolescents

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

• 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 developed infections more frequently than adults.
• Children should receive all recommended vaccines before starting treatment with Flixabi. Children may receive some vaccines during treatment with Flixabi, but they must not receive live microbial vaccines while using Flixabi.

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

Other medicines and Flixabi

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Patients with inflammatory diseases may already be taking medications to treat their condition. These medicines may cause adverse effects. Your doctor will advise you which other medicines you should continue using while on Flixabi treatment.

In particular, inform your doctor if you are taking any of the following medicines:

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

You must not receive live microbial vaccines (e.g., the BCG vaccine against tuberculosis) while using Flixabi. If you were using Flixabi during pregnancy, or if you are receiving Flixabi while breastfeeding, inform your baby’s doctor and other healthcare professionals about your Flixabi treatment before your baby receives any vaccine.

If you are unsure whether 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 considers it necessary.
• You should avoid becoming pregnant while being treated with Flixabi and for 6 months after stopping treatment. Discuss the use of contraception during this time with your doctor.
• If you received Flixabi during pregnancy, your baby may have an increased risk of infection.
• It is important to inform your baby’s doctors and other healthcare professionals about your Flixabi treatment before your baby is vaccinated. If you received Flixabi during pregnancy, administering the BCG vaccine (used to prevent tuberculosis) to your baby within 12 months after birth may lead to infection with serious complications, including death. Live microbial vaccines such as the BCG vaccine must not be given to your baby 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 to inform your baby’s doctors and other healthcare professionals about your Flixabi treatment before your baby is vaccinated. Live microbial vaccines must not be given to your baby while you are breastfeeding unless your baby’s doctor recommends otherwise.
• In infants born to women treated with Flixabi during pregnancy, a severe decrease in white blood cell count has been reported. If your baby has persistent fever or infections, contact your baby’s doctor immediately.

Driving and using machines

The effect of Flixabi on the ability to drive and use machines is minor; for example, dizziness and vertigo.

Flixabi contains sodium

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

Flixabi contains polysorbate 80

This medicine contains 0.5 mg of polysorbate 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 allergies.

3. How Flixabi will be administered to you

Rheumatoid arthritis

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

Psoriatic arthritis, ankylosing spondylitis (Bechterew's disease), psoriasis, ulcerative colitis, and Crohn's disease

The usual dose is 5 mg per kg 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 given as an intravenous infusion (over 2 hours), usually into a vein in your arm. After the third treatment, your doctor may decide to administer your Flixabi dose over 1 hour.
• You will be monitored during administration of Flixabi and also for 1 to 2 hours afterwards.

How much Flixabi will be administered to you

• Your doctor will decide your dose and how often you will receive Flixabi. This will depend on your condition, your body weight, and your response to Flixabi.
• The table below shows how often this medicine is usually administered after your first dose.

2nd dose	2 weeks after your 1st dose
3rd dose	6 weeks after your 1st dose
Additional doses	Every 6 to 8 weeks, depending on your disease

Use in children and adolescents

Flixabi should only be used in children and adolescents 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

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

If you miss or do not attend your Flixabi infusion

If you miss or do not attend an appointment to receive Flixabi, schedule a new appointment as soon as possible.

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

4. Possible adverse effects

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

Contact your doctor immediately 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 swallowing or breathing, skin rash, hives, swelling of the hands, feet or ankles. Some of these reactions may be serious or potentially fatal. An allergic reaction may occur within 2 hours of your infusion or later. Additional signs of allergic adverse reactions may occur up to 12 days after your infusion, such as muscle pain, fever, joint or jaw pain, sore throat, or headache.

• Signs of a heart problem such 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, fatigue, cough which may be persistent, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhoea, abscesses, dental problems or a burning sensation when urinating.

• Possible signs of cancer including, but not limited to, swollen lymph nodes, weight loss, fever, unusual skin lumps, changes in moles or skin colour, or unusual vaginal bleeding.

• Signs of a lung problem such as cough, 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 the face, arm or leg, especially on one side of the body; sudden confusion, difficulty speaking or understanding; sudden vision problems in one or both eyes, difficulty walking, dizziness, loss of balance or coordination, or a severe headache), seizures, numbness/tingling anywhere in the body, or weakness in arms or legs, vision disturbances such as double vision or other eye problems.

• Signs of a liver problem (including hepatitis B infection, when you have previously had hepatitis B) such as yellowing of the skin or eyes, dark brown urine, pain or swelling in the upper right part of the stomach, joint pain, skin rash, or fever.

• Signs of an immune system disorder such as joint pain or a sun-sensitive rash on the cheeks or arms (lupus), or cough, difficulty breathing, fever or skin rash (sarcoidosis).

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

• Signs of serious skin problems such as target-like red or circular patches, often with central blisters on the trunk, large areas of peeling or sloughing skin, mouth, throat, nose, genital or eye ulcers, or small pus-filled lumps that may spread over the body. These skin reactions may be accompanied by fever.

Contact your doctor immediately if you notice any of the above.

The following adverse 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
• Adverse reaction due to an infusion
• 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 or painful breathing, chest pain
• Bleeding in the stomach or intestines, diarrhoea, indigestion, heartburn, constipation
• Hives-type rash (wheals), itchy rash or dry skin
• Balance problems or dizziness
• Fever, increased sweating
• Circulatory problems such as low or high blood pressure
• Bruising, hot flush or nosebleed, warmth, redness of the skin (rubefaction)
• Fungal skin infection
• Feeling tired or weak
• Bacterial infections such as sepsis, abscess or skin infection (cellulitis)
• Fungal skin infection
• Blood problems such as anaemia or low white blood cell count
• Swollen lymph nodes
• Depression, sleep problems
• Eye problems, including red eyes and infections
• Rapid 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
• Numbness or tingling sensation

Uncommon (may affect up to 1 in 100 people)

• Poor blood supply, swelling of a vein
• Blood accumulation outside blood vessels (haematoma) or bruising
• Skin problems such as blisters, warts, abnormal skin colouring or pigmentation, swollen lips, skin thickening, redness, scaly or peeling skin
• Severe allergic reactions (e.g. anaphylaxis), an immune system disorder called lupus, allergic reactions to foreign proteins
• Wounds that heal slowly
• Inflammation of the liver (hepatitis) or gallbladder, liver damage
• Feeling forgetful, irritable, confused, nervous
• Eye problems, including blurred or reduced vision, swollen eyes or styes
• Heart malfunction or worsening of heart condition, decreased heart rate
• Fainting
• Seizures, nerve problems
• Intestinal ulcer or intestinal obstruction, stomach pain or cramps
• Inflammation of the pancreas (pancreatitis)
• Fungal infections such as yeast infection or fungal nail infection
• Lung problems (such as oedema)
• Fluid around the lungs (pleural effusion)
• Narrowing of the airways in the lungs, causing difficulty breathing
• Inflammation of the membrane protecting the lung, causing severe chest pain that worsens with breathing (pleurisy)
• Tuberculosis
• Kidney infections
• Low platelet count, too many white blood cells in blood
• Vaginal infections
• 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 supply enough oxygen to your body, circulatory problems such as narrowing of a blood vessel
• Inflammation of the membranes protecting the brain (meningitis)
• Infections due to a weakened immune system
• Hepatitis B infection, when you have previously had hepatitis B
• Liver inflammation caused by an immune system problem (autoimmune hepatitis)
• Liver problem causing yellowing of the skin and eyes (jaundice)
• Swelling or abnormal growth of tissues
• Severe allergic reaction which may cause loss of consciousness and may be potentially fatal (anaphylactic shock)
• Inflammation of small blood vessels (vasculitis)
• Immune system disorders that may 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
• 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 red-purple rash and/or thick white-grey lines on mucous membranes), blisters and peeling skin, or boils (furunculosis)
• Severe nervous system disorders such as transverse myelitis, multiple sclerosis-like illness, optic neuritis and Guillain-Barré syndrome
• Inflammation in the eye which may cause changes in vision, including blindness
• Fluid in the membrane protecting 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 the number of white blood cells in the blood
• Small red or purple spots caused by bleeding under the skin
• Abnormal levels of a blood protein called “complement factor” which is part of the immune system.

Frequency not known (cannot be estimated from available data)

• Cancer in children and adults

• A rare blood cancer affecting mainly 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 associated with human herpesvirus 8 infection. Kaposi’s sarcoma usually presents more frequently as purplish skin lesions.

• Worsening of a disease called dermatomyositis (manifested as 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 microorganism vaccine because of a weakened immune system.

• Complications following a medical procedure (including infectious and non-infectious complications)

Other adverse effects in children and adolescents

Children and adolescents treated with infliximab for Crohn’s disease showed some differences in adverse effects compared to adults treated with infliximab for Crohn’s disease. Adverse effects that occurred more frequently in children were: low red blood cells (anaemia), blood in stools, low total white blood cell counts (leucopenia), facial redness or flushing (rubefaction), viral infections, low levels of white blood cells fighting infection (neutropenia), bone fracture, bacterial infection and allergic reactions of the respiratory tract.

Reporting of adverse effects

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

By reporting adverse 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 stated on the label and on the carton after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2°C and 8°C).
• This medicine may also be stored in its original carton outside the refrigerator at a maximum temperature of 25°C for a single period not exceeding six months, but without exceeding the original expiry date. In this case, do not return it to the refrigerator. Write the new expiry date on the carton as day/month/year. Discard this medicine if it has not been used before the new expiry date or the expiry date indicated on the carton, whichever comes first.
• When preparing Flixabi for infusion, it is recommended to use it as soon as possible (within 3 hours). However, if the solution is prepared under germ-free conditions, it may be stored in a refrigerator at 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 there is any change in colour or if particles are present.

6. Contents of the pack and other information

Composition of Flixabi

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

Nature and contents of the container

Flixabi is supplied as 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 vial(s). Only certain pack sizes may be marketed.

Marketing Authorization 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

The Netherlands

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

For further information about this medicine, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium Biogen Belgium NV/S.A Tel/Tel: + 32 2 219 1218	Lithuania Biogen Lithuania UABTel: +370 5 259 617
	Luxembourg/Luxembourg Biogen Belgium NV/SA Tel/Tel: +32 219 1218
Czech Republic Biogen (Czech Republic) s.r.o. Tel: + 420 255 706 20	Hungary Biogen Hungary Kft. Tel.: + 36 1 899 9880
Denmark Biogen (Denmark) A/S Tlf.: + 45 77 41 57 57	Malta Pharma.MT Ltd Tel: + 356 2133 7008
Germany Biogen GmbH Tel: + 49 (0) 89 99 617	Netherlands Biogen Netherlands B.V. Tel: + 31 20 542 2000
Estonia Biogen Estonia OÜ Tel: + 372 618 9551	Norway Biogen Norway AS Tlf: + 47 23 40 01 00
Greece Genesis Pharma S.A. Tel: + 30 210 877 1500	Austria Biogen Austria GmbH Tel: + 43 1 484 46 13
Spain Biogen Spain, S.L. Tel: : + 34 91 310 7110	Poland Biogen Poland Sp. z o.o. Tel.: + 48 22 351 51 00
France Biogen France SAS Tél: + 33 (0)1 776 968 14	Portugal Biogen Portugal Sociedade Farmacêutica, Unipessoal, Lda Tel: + 351 21 318 8450
Croatia Ewopharma d.o.o Tel: + 385 (0)1 6646 563	Romania Ewopharma Romania SRL Tel: + 40 212 601 344
Ireland Biogen Idec (Ireland) Ltd. Tel: +353 (0)1 463 7799	Slovenia Biogen Pharma d.o.o. Tel: + 386 1 511 02 90
Iceland Icepharma hf. Tel: + 354 540 8000	Slovakia Biogen Slovakia s.r.o. Tel: + 421 2 323 340 08
Italy Biogen Italia s.r.l. Tel: + 39 02 584 99 010	Finland/Finland Biogen Finland Oy Tel/Tel: + 358 207 401 200
Cyprus Genesis Pharma (Cyprus) Ltd Tel: + 357 22 76 57 15	Sweden Biogen Sweden AB Tel: +46 8 594 113 60
Latvia Biogen Latvia SIA Tel: + 371 68 688 158

Date of last review of this summary: 05/2025

Other sources of information

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

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This information is intended for healthcare professionals only:

Patients treated with Flixabi must be provided with the patient information card.

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

Instructions for use and handling – storage conditions

Store between 2°C and 8°C.

Flixabi may be stored at a maximum temperature of 25°C for a single period not exceeding 6 months, but without exceeding the original expiry date. The new expiry date must be written on the carton. Once removed from refrigerated conditions, Flixabi must not be returned to refrigerated storage.

Instructions for use and handling – reconstitution, dilution and administration

To improve the traceability of biological medicinal products, the trade name and batch number of the administered product must be clearly documented.

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

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 the cap from the vial and clean the top with a cotton swab moistened with 70% alcohol. Insert the syringe needle into the vial in the center of the rubber stopper and direct the water for injections onto the glass wall of the vial. Gently swirl the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous shaking. DO NOT SHAKE. Formation of foam during reconstitution is not uncommon, as infliximab is a protein. Allow the reconstituted solution to stand for 5 minutes. Check that the solution is colorless to pale yellow and opalescent. A few fine translucent particles may be visible in the solution, due to the nature of infliximab as a protein. Do not use if the solution contains opaque particles, discoloration, or other foreign particles.

3. Dilute the total 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. Dilution may be performed by removing from the glass infusion bottle or infusion bag of 250 ml a volume of 9 mg/ml (0.9%) sodium chloride solution for infusion equal to the volume of reconstituted Flixabi. Slowly add the total volume of reconstituted Flixabi solution to the 250 ml infusion bottle or bag. Mix gently. For volumes exceeding 250 ml, use a larger infusion bag (e.g., 500 ml, 1000 ml) or multiple 250 ml infusion bags to ensure that the concentration in the infusion solution does not exceed 4 mg/ml. If the infusion solution is refrigerated after reconstitution and dilution, allow it to reach room temperature (25°C) for 3 hours prior to step 4 (infusion). Storage beyond 24 hours at 2°C–8°C applies only to Flixabi preparations in the infusion bag.

4. Administer the infusion solution over a period no shorter than the recommended infusion time. Use only an infusion set with a low-protein-binding, non-pyrogenic, sterile filter (pore size 1.2 micrometers or smaller). Since the product contains no preservatives, it is recommended that administration of the infusion solution begin as soon as possible and within 3 hours of reconstitution and dilution. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2°C–8°C, unless reconstitution/dilution has been carried out under controlled and validated aseptic conditions. Do not store any unused portion of the infusion solution for later reuse.

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

6. Prior to administration, visually inspect Flixabi for particles or discoloration. Do not use if visible opaque particles, discoloration, or foreign particles are observed.

7. Disposal of unused medicinal product and all materials that have come into contact with it must be carried out in accordance with local regulations.