Remsima 100 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Remsima 100 mg powder for concentrate for solution for infusion

infliximab

Read the entire 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 provide you with a patient information card containing important safety information you need to know before and during your treatment with Remsima.
• When starting a new card, keep this card as a reference for 4 months after your last dose of Remsima.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Remsima is and what it is used for

Remsima 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 (tumour necrosis factor) alpha.

Remsima belongs to a group of medicines known as “TNF blockers”. It is used in adults for the following inflammatory diseases:

• Rheumatoid arthritis
• Psoriatic arthritis
• Ankylosing spondylitis (Bechterew’s disease)
• Psoriasis

Remsima is also used in adults and children from 6 years of age for:

• Crohn’s disease
• Ulcerative colitis

Remsima 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, inflammation in your body can be reduced.

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 Remsima together with another medicine called methotrexate to:

• reduce the signs and symptoms of your disease,
• slow down 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 Remsima 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 medicines do not work well enough, you will be given Remsima 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 Remsima 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 Remsima 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 Remsima to:

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

2. What you need to know before using Remsima

Do not use Remsima if:

• you are allergic to infliximab or to any of the other components of Remsima (listed in section 6),
• you are allergic to proteins derived from mice,
• you have tuberculosis (TB) or another serious infection such as pneumonia or septicemia (a severe bacterial blood infection),
• you have moderate or severe heart failure.

If any of the above apply to you, do not use Remsima. If you are unsure, consult your doctor before receiving Remsima.

Warnings and precautions

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

You have previously received treatment with any medicine containing infliximab

• Inform your doctor if you have previously been treated with medicines containing infliximab and are now restarting treatment with Remsima.
• 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 receiving Remsima, tell your doctor if you have an infection, even if it is mild.
• Before receiving Remsima, tell 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 the body.
• You may be more susceptible to infections while being treated with Remsima. If you are 65 years of age or older, your risk is higher.
• These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other environmental organisms, and septicemia, which can potentially be fatal.

Contact your doctor immediately if you notice signs of infection during treatment with Remsima, 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 Remsima.

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 or had TB.
• Your doctor will perform a test to check for TB. Cases of TB have been reported in patients treated with infliximab, including in patients who have previously been treated for TB. Your doctor will record these test results on your patient information card.
• If your doctor considers you at risk for TB, you may be treated with anti-TB medications before starting Remsima.

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

Hepatitis B virus

• Before receiving Remsima, 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 should perform tests for hepatitis B virus.
• Treatment with TNF blockers such as Remsima may cause reactivation of hepatitis B virus in carriers, which in some cases can be potentially fatal.
• If you experience reactivation of hepatitis B, your doctor may need to discontinue your treatment and may prescribe effective antiviral therapy and supportive treatment.

Heart problems

• Inform your doctor if you have any heart problems, such as mild heart dysfunction (mild heart failure).
• Your doctor will want to closely monitor your heart.

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

Cancer and lymphoma

• Before receiving Remsima, inform your doctor if you have or have ever had lymphoma (a type of blood cancer) or any other cancer.
• Patients with severe rheumatoid arthritis who have had the disease for a long time may have an increased risk of developing lymphoma.
• Children and adults treated with Remsima may have an increased risk of developing lymphoma or other types of cancer.
• Some patients who have received TNF blockers, including infliximab, 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 is usually fatal. Almost all of these patients had also received azathioprine or 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 skin changes or skin growths during or after treatment.
• Some women receiving infliximab for rheumatoid arthritis have developed cervical cancer. Women treated with Remsima, even those over 60 years of age, may be advised by their doctor to have regular cervical cancer screenings.

Lung disease or heavy smokers

• Before receiving Remsima, 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 during treatment with Remsima.

Nervous system disorders

• Inform your doctor if you have or have ever had a condition affecting your nervous system before receiving Remsima. 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 Remsima. Symptoms may include changes in vision, weakness in arms or legs, numbness, or tingling anywhere in the body.

Abnormal skin openings

• Consult your doctor if you have an abnormal skin ulcer (fistula) before receiving Remsima.

Vaccines

• Talk to your doctor if you have recently received or need to receive a vaccine.
• Before starting treatment with Remsima, you should receive all recommended vaccines. You may receive certain vaccines during treatment with Remsima, but you must not receive live microbial vaccines (vaccines containing a live but weakened infectious agent) while using Remsima, as they may cause infections.
• If you received Remsima during pregnancy, your baby may also have an increased risk of infection from receiving live microbial vaccines during the first year of life. It is important to inform your baby’s doctors and other healthcare professionals about your Remsima 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 Remsima treatment before your baby receives any vaccine. For more information, see the section on Pregnancy, breastfeeding, and fertility.

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 to treat cancer).

Surgery or dental procedures

• Inform your doctor if you are scheduled for surgery or a dental procedure.
• Inform your surgeon or dentist that you are being treated with Remsima and show them your patient information card.

Liver problems

• Some patients receiving Remsima have developed serious liver problems.
• Contact your doctor immediately if you notice symptoms of liver problems during treatment with Remsima. 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 rashes, or fever.

Low blood cell counts

• In some patients receiving Remsima, 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 Remsima. Symptoms may include persistent fever, bleeding or bruising easily, small red or purple spots under the skin caused by bleeding, or paleness.

Immune system disorders

• Some patients who have received Remsima have developed symptoms of an immune system disorder called lupus.
• Contact your doctor immediately if you develop symptoms of lupus during treatment with Remsima. 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 infliximab have developed cancers, including rare types, some of which have been fatal.
• More children treated with infliximab developed infections compared to adults.
• Children should receive all recommended vaccines before starting treatment with Remsima. Children may receive some vaccines during treatment with Remsima, but they must not receive live microbial vaccines while using Remsima.

Remsima should only be used in children being treated for Crohn’s disease or ulcerative colitis. These children must be 6 years of age or older.

If you are unsure whether any of the above apply to you, consult your doctor before receiving Remsima.

Other medicines and Remsima

Patients with inflammatory diseases are often already taking medicines to treat their condition. These medicines may cause side effects. Your doctor will advise you on which other medicines you should continue using during treatment with Remsima.

Inform your doctor if you are using, have recently used, or might need to use any other medicine, including other medicines for Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis, or over-the-counter medicines such as vitamins or herbal remedies.

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

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

You must not receive live microbial vaccines while using Remsima. If you used Remsima during pregnancy or are receiving Remsima while breastfeeding, inform your baby’s doctor and other healthcare professionals about your Remsima treatment before your baby receives any vaccine.

If you are unsure whether any of the above apply to you, consult your doctor or pharmacist before starting treatment with Remsima.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Remsima should only be used during pregnancy or breastfeeding if your doctor considers it necessary.
• You should avoid becoming pregnant while being treated with Remsima and for 6 months after stopping treatment. Discuss the use of contraceptive measures during this time with your doctor.
• If you received Remsima 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 Remsima treatment before your baby is vaccinated. If you received Remsima during pregnancy, administering the BCG vaccine (used to prevent tuberculosis) to your baby within 12 months of birth may lead to infection with serious complications, including death. Live microbial vaccines such as the BCG vaccine should 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 Remsima treatment before your baby is vaccinated. Live microbial vaccines should not be given to your baby while you are breastfeeding unless your baby’s doctor recommends otherwise.
• In infants born to women treated with infliximab during pregnancy, a serious 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

It is unlikely that Remsima will affect your ability to drive or use tools or machinery. However, if you feel tired, dizzy, or unwell after receiving Remsima, do not drive or use tools or machinery.

Remsima contains sodium

Remsima contains less than 1 mmol of sodium (23 mg) per dose; therefore, it is essentially "sodium-free." However, before administration, Remsima is mixed with a solution containing sodium. Consult your doctor if you are on a low-salt diet.

Remsima contains polysorbate 80

This medicine contains 0.5 mg of polysorbate 80 per vial. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How Remsima 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 Remsima will be administered to you

• Remsima will be administered by your doctor or nurse.
• Your doctor or nurse will prepare the medicine for infusion.
• The medicine will be given as an intravenous infusion (drip) over 2 hours, usually into a vein in your arm. After the third treatment, your doctor may decide to administer your dose of Remsima over 1 hour.
• You will be monitored during administration of Remsima and for 1 to 2 hours afterwards.

How much Remsima will be administered to you

• Your doctor will determine your dose and how often Remsima will be administered. This will depend on your condition, body weight, and your response to Remsima.
• 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 condition

Use in children and adolescents

In children (6 years of age or older) being treated for Crohn's disease or ulcerative colitis, the recommended dose is the same as that for adults.

If you are given too much Remsima

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

If you missed or did not attend your Remsima infusion

If you missed or did not attend an appointment to receive Remsima, schedule a new appointment as soon as possible. If you have any further questions about the use of this medicine, consult your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets 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 Remsima has ended.

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

• Signs of an allergic reaction such as swelling of the 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. Other allergic adverse effects 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, shortness of breath, 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, cough which may be persistent, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhoea, wounds, pus accumulation in the abdomen or around the anus (abscess), dental problems or a burning sensation when urinating.
• Possible signs of cancer including, but not limited to, swollen lymph nodes, weight loss, fever, uncommon skin nodules, changes in moles or skin colouring, 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; difficulty seeing with 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 had hepatitis B previously) such as yellowing of the skin and 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 called lupus such as joint pain or a sun-sensitive rash on 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 or circular red patches, often with central blisters on the trunk, large areas of peeling and sloughing skin (exfoliation), 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.

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

The following adverse effects have been observed with Remsima:

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 skin 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 (flushing)
• 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), 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 heartbeat
• Fainting
• Seizures, nerve problems
• Intestinal ulcer or intestinal obstruction, stomach pain or cramps
• Inflammation of the pancreas (pancreatitis)
• Fungal infections such as Candida 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 on breathing (pleurisy)
• Tuberculosis
• Kidney infections
• Low platelet count, too many white blood cells in blood, bruises or black or blue marks
• 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 1,000 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 had hepatitis B previously
• Inflammation of the liver 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 that 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)
• 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 generalised exanthematous pustulosis
• Other skin problems such as erythema multiforme, blisters and peeling of the skin, or boils (furunculosis)
• Serious nervous system disorders such as transverse myelitis, multiple sclerosis-like disease, optic neuritis and Guillain-Barré syndrome
• Inflammation in the eye that may cause changes in vision, including blindness
• Fluid in the membrane protecting 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 drop in the number of white blood cells in blood
• Small red or purple spots caused by bleeding under the skin
• Abnormal values of a blood protein called “complement factor” which is part of the immune system
• Lichenoid reactions (itchy red-purple skin rash and/or thick white-greyish lines on mucous membranes).

Frequency not known: cannot be estimated from the 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, an uncommon cancer associated with human herpesvirus 8 infection. Kaposi’s sarcoma usually presents more frequently as purple-coloured 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 organism vaccine because of a weakened immune system
• Problems following a medical procedure (including infectious and non-infectious problems).

Other adverse effects in children and adolescents

Children 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, generally low white blood cell counts (leucopenia), facial redness or flushing (flushing), viral infections, low levels of infection-fighting white blood cells (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 via 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 Remsima

Remsima is normally stored by healthcare professionals. If you require storage details, they 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 the carton after EXP. The expiry date refers to the last day of the month indicated.
• Store in a refrigerator (between 2°C – 8°C).
• This medicine may also be stored in its original carton outside the refrigerator at temperatures up to 25°C for a single period of up to six months, provided the original expiry date is not exceeded. In this case, the medicine must not be refrigerated again. Write the new expiry date on the carton, including day/month/year. Discard this medicine if not used by the new expiry date or by the expiry date printed on the carton, whichever comes first.
• When preparing Remsima for infusion, it is recommended to use it as soon as possible (within 3 hours). However, if the solution is prepared under aseptic conditions, it may be stored in a refrigerator at 2°C – 8°C for up to 60 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 container and other information

Composition of Remsima

• 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 (E433), monosodium dihydrogen phosphate monohydrate and disodium hydrogen phosphate dihydrate.

Appearance of the product and contents of the container

Remsima is presented as a glass vial containing a white powder for concentrate for solution for infusion.

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

Marketing Authorisation Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B tower

Hungary

Manufacturer

Nuvisan GmbH

Wegenerstraße 13,

89231 Neu Ulm,

Germany

Nuvisan France SARL

2400, Route des Colles,

06410, Biot,

France

Kymos, SL

Ronda De Can Fatjó 7B, Parc Tecnològic del

Vallès, Cerdanyola del Vallès,

Barcelona,

08290, Spain

Midas Pharma

GmbH Rheinstraße 49

55218 Ingelheim am Rhein

Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Belgium/Belgique/Belgien Celltrion Healthcare Belgium BVBA Tel/Tel: +32 1528 7418	Lithuania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
	Luxembourg/Luxemburg Celltrion Healthcare Belgium BVBA Tel/Tel: +32 1528 7418
Czech Republic Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493	Hungary Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Denmark Orion Pharma A/S Tlf: +45 86 14 00 00	Malta Mint Health Ltd. Tel: +356 2093 9800 [email protected]
Germany Celltrion Healthcare Deutschland GmbH Tel: +49 30 346494150 [email protected]	Netherlands Celltrion Healthcare Netherlands B.V. Tel: +31 20 888 7300
Estonia Orion Pharma Eesti OÜ Tel: +372 6 644 550	Norway Orion Pharma AS Tlf: +47 40 00 42 10
Greece BIANEX S.A. Tel: +30 210 8009111 – 120	Austria Astro-Pharma GmbH Tel.: +43 1 97 99 860 [email protected]
Spain Kern Pharma, S.L. Tel: +34 93 700 25 25	Poland Celltrion Healthcare Hungary Kft. Tel.: +36 1 231 0493
France Celltrion Healthcare France SAS Tel: +33 (0)1 71 25 27 00	Portugal Celltrion Portugal, Unipessoal Lda. Tel: +351 21 936 8542
Croatia OKTAL PHARMA d.o.o. Tel: +385 1 6595 777 [email protected]	Romania Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Ireland Celltrion Healthcare Ireland Limited Tel: +353 1 223 4026	Slovenia OPH Oktal Pharma d.o.o. Tel: +386 1 519 29 22 [email protected]
Iceland Vistor hf. Sími: +354 535 7000	Slovakia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493
Italy Celltrion Healthcare Italy S.r.l. Via Luigi Galvani, 24 - 20124 Milano (MI) Tel: +39 0247 927040	Finland/Sweden Orion Pharma Puh/Tel: +358 10 4261
Cyprus C.A. Papaellinas Ltd Tel: +357 22741741	Sweden Orion Pharma AB Tel: +46 8 623 64 40
Latvia Celltrion Healthcare Hungary Kft. Tel: +36 1 231 0493

Date of the most recent review of this leaflet: {MM/YYYY}

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

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

Instructions for use and handling – storage conditions

Store at 2°C – 8°C.

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

Instructions for use and handling: reconstitution, dilution, and administration

To improve traceability of biological medicines, the brand name and batch number of the administered medicine should be clearly recorded.

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

2. Under aseptic conditions, reconstitute each vial of Remsima 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 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 agitation. DO NOT SHAKE THE VIAL. Foam may form during reconstitution. Allow the reconstituted solution to stand for 5 minutes. Check that the solution is colourless to pale yellow and opalescent. A few fine translucent particles may be visible, as infliximab is a protein. Do not use the solution if it contains opaque particles, discolouration, or other foreign particles.

3. The required volume of reconstituted Remsima solution should be diluted to a final volume of 250 mL with 9 mg/mL (0.9%) sodium chloride solution for infusion. Do not dilute the reconstituted Remsima solution with any other diluent. Dilution can be performed by removing from the glass bottle or infusion bag containing 250 mL of 9 mg/mL (0.9%) sodium chloride solution for infusion a volume equal to the volume of reconstituted Remsima. The required volume of reconstituted Remsima solution should then be slowly added to the bottle or infusion bag and gently mixed. For volumes exceeding 250 mL, use a larger infusion bag (e.g., 500 mL, 1,000 mL) or multiple 250 mL infusion bags to ensure that the final concentration in the infusion solution does not exceed 4 mg/mL. If the solution for infusion is refrigerated after reconstitution and dilution, allow it to reach room temperature (25°C) for 3 hours before proceeding to Step 4 (infusion). Storage beyond 24 hours at 2°C–8°C applies only to Remsima preparations in the infusion bag.

4. Administer the infusion solution over a period no shorter than the recommended infusion time (see section 3). Use only an infusion set with a low-protein-binding, non-pyrogenic, sterile filter (pore size 1.2 micrometres or smaller). Since no preservatives are included, administration of the infusion solution should 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 was carried out under controlled and validated aseptic conditions. Do not store any unused portion of the infusion solution for later use.

5. Prior to administration, Remsima should be inspected visually for particulate matter and discoloration. Do not use if visible opaque particles, discoloration, or foreign particles are observed.

6. Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.