REMSIMA 100 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the User

Remsima 100 mg 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 your treatment with Remsima.
• When you start a new card, keep this card as a reference for 4 months after your last dose of Remsima.
• If you have any further questions, ask your doctor.
• This medicine has been prescribed for you only, do not pass it on to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Remsima and what is it used for

Remsima contains the active substance infliximab. Infliximab is a monoclonal antibody – a type of protein that targets a specific goal in the body called TNF (tumour necrosis factor) alpha.

Remsima 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.

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 the inflammatory processes of 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 Remsima with another medicine called methotrexate to:

• reduce the signs and symptoms of your disease,
• slow down the damage to your joints,
• improve your physical condition.

Psoriatic Arthritis

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

• reduce the signs and symptoms of your disease,
• reduce the damage to your joints,
• improve your physical condition.

Ankylosing Spondylitis (Bechterew's disease)

Ankylosing spondylitis is an inflammatory disease of the spine. If you have ankylosing spondylitis, you will first be given other 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 condition.

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 channels (fistulas) between your intestine and your skin, that have not been controlled by other medicines or surgery.

2. What you need to know before you start using Remsima

Remsima must not be given to you if:

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

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

Warnings and precautions

Consult your doctor before or during treatment with Remsima if:

You have previously received treatment with any medicine that contains infliximab

• Tell your doctor if you have received treatment with medicines that contain infliximab in the past and now start new treatment with Remsima.
• 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 Remsima, tell your doctor if you have an infection, even if it is mild.
• Before you are given Remsima, tell your doctor if you have ever lived or traveled to a place 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 Remsima. If you are 65 years of age or older, 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 septicemia, which can be life-threatening.

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

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 infliximab, even in patients who have already 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 Remsima.

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

Hepatitis B virus

• Before you are given Remsima, tell your doctor if you are a carrier of hepatitis B or if you have ever had it.
• 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 Remsima, may cause reactivation of the hepatitis B virus in patients who are carriers of this virus, which in some cases can be life-threatening.
• If you experience reactivation of hepatitis B, your doctor may need to stop your treatment, and may give you medicines such as effective antiviral therapy with supportive treatment.

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 Remsima. The signs include difficulty breathing or swelling of the feet.

Cancer and lymphoma

• Before you are given Remsima, tell 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 a higher risk of developing lymphoma.
• Children and adults treated with Remsima may have a higher 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 or young adult males and most had Crohn's disease or ulcerative colitis. This type of cancer is usually fatal. Almost all patients had also received medicines with azathioprine or 6-mercaptopurine, in addition to TNF blockers.
• Some patients treated with infliximab have developed certain types of skin cancer. Tell your doctor if you notice any changes in your skin or growths on your skin during or after treatment.
• Some women treated with infliximab for rheumatoid arthritis have developed cervical cancer. Women treated with Remsima, even those over 60 years of age, may be recommended regular cervical cancer screening by their doctor.

Lung disease or heavy smoking

• Before you are given Remsima, 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 Remsima.

Nervous system disease

• Tell your doctor if you have or have ever had a problem that affects your nervous system before you are given Remsima. 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 Remsima. The symptoms can be changes in vision, weakness in the arms or legs, numbness or tingling in any part of the body.

Abnormal skin openings

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

Vaccines

• Consult your doctor if you have recently had or are scheduled to have a vaccine.
• Before starting treatment with Remsima, you should receive the recommended vaccines. You can receive some vaccines during treatment with Remsima, but you must not receive live virus vaccines (vaccines that contain a live but weakened infectious agent) while you are using Remsima, as they may cause infections.
• If you received Remsima while you were pregnant, your baby may also have a higher risk of getting an infection as a result of receiving a live virus 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 Remsima so that they can decide when your baby can be vaccinated, including live virus 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 Remsima before your baby is vaccinated. You must not give your baby live virus vaccines 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 a BCG instillation used for cancer treatment).

Operations 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 Remsima, and show them your patient information card.

Liver problems

• Some patients who received Remsima have developed severe liver problems.
• Tell your doctor immediately if you notice symptoms of liver problems during treatment with Remsima. The symptoms can be yellowing of the skin and eyes, dark brown urine, pain or swelling in the upper right side of the stomach, joint pain, skin rash, or fever.

Low blood cell counts

• In some patients who receive Remsima, the body may not be able to 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 Remsima. 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 Remsima have developed symptoms of an immune system disorder called lupus.
• Tell your doctor immediately if you develop symptoms of lupus during treatment with Remsima. The symptoms can be joint pain or a rash on the cheeks or arms due to sun sensitivity.

Children and adolescents

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

• Some children and adolescents treated with TNF blockers like infliximab have developed cancers, including rare types, which in some cases have been fatal.
• More children treated with infliximab have developed infections compared to adults.
• Children should receive the recommended vaccines before starting treatment with Remsima. Children can receive some vaccines during treatment with Remsima, but they must not receive live virus vaccines while they are using Remsima.

Remsima should only be used in children 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 not sure if any of the above applies to you, consult your doctor before you are given Remsima.

Other medicines and Remsima

Patients who have 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 Remsima.

Tell your doctor if you are using, have recently used, or could be taking any other medicine, including any other medicine for the treatment of Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis, or medicines bought without a prescription, such as vitamins or herbal remedies.

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

• Medicines that affect your immune system.
• Kineret (which contains anakinra). Remsima and Kineret must not be used at the same time.
• Orencia (which contains abatacept). Remsima and Orencia must not be used at the same time.

You must not receive live virus vaccines while you are using Remsima. If you were using Remsima during pregnancy or if you are receiving Remsima during breastfeeding, tell your baby's doctor and other healthcare professionals about your treatment with Remsima 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 you start using Remsima.

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. Remsima should only be used during pregnancy or breastfeeding if your doctor considers it necessary for you.
• You should avoid becoming pregnant while you are being treated with Remsima and for 6 months after treatment has finished. Discuss the use of contraceptive measures during this time with your doctor.
• If you received Remsima 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 Remsima before your baby is vaccinated. If you received Remsima while you were pregnant, giving your baby the BCG vaccine (used to prevent tuberculosis) within 12 months after birth may cause infection with serious complications, including death. Your baby must not receive live virus 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 Remsima before your baby is vaccinated. Your baby must not receive live virus vaccines while you are breastfeeding, unless your baby's doctor recommends otherwise.
• In children born to women treated with infliximab during pregnancy, a serious decrease in the number of white blood cells in the blood has been reported. If your baby has fevers or persistent 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 machines. If you feel tired, dizzy, or unwell after you are given Remsima, do not drive or use tools or machines.

Remsima contains sodium

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

3. How Remsima will be given 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 Remsima will be given to you

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

How much Remsima will be given to you

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

Use in children and adolescents

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

If you are given too much Remsima

As this medicine is being given to you by your doctor or nurse, it is unlikely that you will be given too much Remsima. The effects of overdose of Remsima are not known.

If you miss or do not attend your Remsima infusion

If you miss or do not attend a scheduled infusion of Remsima, make an appointment as soon as possible. If you have any other 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 all people suffer from them. Most adverse effects are mild to moderate. However, some patients may experience serious adverse effects and may require treatment. Adverse effects can also occur after your treatment with Remsima has ended.

Report immediately to your doctor if you notice any of the following:

• Signs of an allergic reactionsuch as swelling of the face, lips, mouth, or throat, which can cause difficulty swallowing or breathing, skin rash, hives, swelling of the 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. Other allergic adverse effects can occur up to 12 days after your injection, such as muscle pain, fever, joint 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, rapid or slow heartbeat, and swelling of the feet.
• Signs of infection (including TB)such as fever, fatigue, persistent cough, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhea, wounds, accumulation of pus in the abdomen or around the anus (abscess), dental problems, or burning sensation while urinating.
• Possible signs of cancerthat include, but are not limited to, swelling of the lymph nodes, weight loss, fever, rare skin nodules, changes in moles or skin color, or rare vaginal bleeding.
• Signs of a lung problemsuch as cough, difficulty breathing, or chest tightness.
• Signs of a nervous system problem (including eye problems)such as 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 the 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 the skin and eyes, dark brown urine, pain or swelling in the upper right side of the stomach, joint pain, skin rash, or fever.
• Signs of an immune system disordersuch 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 countssuch as persistent fever, bleeding, or easy bruising, small red or purple spots caused by bleeding under the skin, or paleness.
• Signs of serious skin problemssuch as red or circular patches on the skin, often with central blisters on the trunk, large areas of peeling skin, ulcers in the mouth, throat, nose, genitals, and eyes, or small pus-filled bumps that can spread across the body. These skin reactions can be accompanied by fever.

Report to 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 effect due to 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
• Difficult or painful breathing, chest pain
• Bleeding in the stomach or intestines, diarrhea, indigestion, heartburn, constipation
• Hives (urticaria), itchy skin rash, or dry skin
• Balance problems or feeling dizzy
• Fever, increased sweating
• Circulation problems such as low or high blood pressure
• Bruising, flushing, or nosebleeds, heat, skin redness (rubefaction)
• 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
• Pain in the joints, muscles, or back
• Urinary tract infection
• Psoriasis, skin problems such as eczema, and hair loss
• Reactions at the injection site such as pain, swelling, redness, or itching
• Chills, 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, abnormal 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 or reduced vision, or swollen eyes with styes
• Heart malfunction or worsening, decreased heart rate
• Fainting
• Seizures, nerve problems
• Intestinal ulcers or obstruction, stomach pain or cramps
• Pancreas inflammation (pancreatitis)
• Fungal infections such as Candida or fungal nail infection
• 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, bruising, or black and 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, the weight gain was small).

Rare:may affect up to 1 in 1,000 people

• A type of blood cancer (lymphoma)
• Your blood not providing enough oxygen to your body, circulation problems such as narrowing of a blood vessel
• Inflammation of the membranes that protect the brain (meningitis)
• Infections due to a weakened immune system
• Hepatitis B infection when you have had hepatitis B 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, blisters, and skin peeling, or boils (furunculosis)
• Severe nervous system problems such as transverse myelitis, multiple sclerosis-like disease, optic neuritis, and Guillain-Barré syndrome
• Inflammation in the eye that can cause vision changes, including blindness
• Fluid in the membrane that protects the heart (pericardial effusion)
• 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 caused by bleeding under the skin
• Abnormal levels of a blood protein called "complement factor" that is part of the immune system
• Lichenoid reactions (itchy red-purple skin rash and/or thick white-gray lines on the mucous membranes).

Frequency not known:cannot be estimated from the available data

• Cancer in children and adults
• A rare type of blood cancer that mainly affects 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 manifests more frequently as purple 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 vaccine because of a weakened immune system.

Other adverse effects in children and adolescents

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

Reporting of adverse effects

If you experience any kind of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Remsima

Remsima will normally be stored by healthcare professionals. 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 that appears on the label and on the carton after EXP. The expiry date is the last day of the month indicated.
• Store in a refrigerator (between 2°C – 8°C).
• This medicine can also be stored in the original carton outside the refrigerator up to a maximum of 25°C for a single period of up to six months, but not beyond the initial expiry date. In this situation, it must not be stored in the refrigerator again. Write the new expiry date on the carton including day/month/year. Discard this medicine if it has not been used by the new expiry date or the expiry date printed on the carton, whichever is earlier.
• It is recommended that when Remsima 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 – 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 the color is altered or particles are present.

6. Container Contents and Additional Information

Remsima Composition

• 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, sodium dihydrogen phosphate monohydrate, and disodium hydrogen phosphate dihydrate.

Product Appearance and Container Contents

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

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

Marketing Authorization Holder

Celltrion Healthcare Hungary Kft.

1062 Budapest

Váci út 1-3. WestEnd Office Building B torony

Hungary

Manufacturer

Millmount Healthcare Ltd.

Block 7

City North Business Campus

Stamullen, Co. Meath K32 YD60

Ireland

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 authorization holder:

Date of Last Revision of this Prospectus: {MM/AAAA}

Other Sources of Information

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

This information is intended for healthcare professionals only:

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

Instructions for Use and Handling – Storage Conditions

Store at 2°C – 8°C.

Remsima can be stored at temperatures up to a maximum of 25°C for a single period of up to 6 months, but without exceeding the initial 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

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

1. The dose and number of Remsima vials must be calculated. Each Remsima vial contains 100 mg of infliximab. The total volume of Remsima reconstituted solution needed must also be calculated.

1. Under aseptic conditions, each Remsima vial must be reconstituted with 10 ml of water for injections, using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. The vial cap must be removed and the top cleaned with a cotton swab moistened with 70% alcohol. The syringe needle must be inserted into the vial through the center of the rubber stopper and the water for injections directed to the glass wall of the vial. Gently swirl the solution by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous agitation. THE VIAL MUST NOT BE SHAKEN. Foam formation may occur during reconstitution. The reconstituted solution must stand for 5 minutes. Check that the solution is colorless to pale yellow and opalescent. A few fine translucent particles may be present in the solution, as infliximab is a protein. The solution must not be used if it contains visible opaque particles, color alteration, or other foreign particles.

1. The required volume of Remsima reconstituted solution must be diluted to 250 ml with infusion solution 9 mg/ml (0.9%) sodium chloride. Do not dilute the Remsima reconstituted solution with any other diluent. Dilution can be performed by withdrawing a volume of the infusion solution 9 mg/ml (0.9%) sodium chloride equal to the volume of Remsima reconstituted solution from a 250 ml glass bottle or infusion bag. The required volume of Remsima reconstituted solution must be slowly added to the 250 ml glass bottle or infusion bag and gently mixed. 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 the infusion solution concentration does not exceed 4 mg/ml. If stored refrigerated after reconstitution and dilution, the infusion solution must be allowed to reach room temperature (25°C) for 3 hours before administration (Step 4). Storage beyond 24 hours at 2°C-8°C applies only to the preparation of Remsima in the infusion bag.

1. Administer the infusion solution over a period of not less than the recommended infusion time (see section 3). Only use an infusion set with an in-line, sterile, non-pyrogenic filter with a pore size of 1.2 microns or less. Since it does not contain preservatives, it is recommended that the administration of the infusion solution begins 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 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. Before administration, Remsima must be visually inspected for particles or color alteration. It must not be used if visible opaque particles, color 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.