Prospect: Information for the User

Remsima 100 mg powder for concentrate for solution for infusion

infliximab

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• Your doctor will also give you a patient information leaflet, which contains important safety information that you need to know before and during your treatment with Remsima.
• When starting a new leaflet, keep this leaflet 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 only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they do not appear in this prospect. See section 4.

Remsima contains the active ingredient infliximab. Infliximab is a monoclonal antibody – a type of protein that binds to a specific target in the body called TNF (tumor necrosis factor) alpha.

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

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

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

• Crohn's disease
• Ulcerative colitis.

Remsima acts by selectively binding to TNF alpha and blocking its action. TNF alpha is involved in the body's inflammatory processes, so blocking it can reduce inflammation in the body.

Rheumatoid Arthritis

Rheumatoid arthritis is an inflammatory disease of the joints. If you have active rheumatoid arthritis, you will first be given other medications. If these medications do not work well enough, you will be given Remsima with another medication called methotrexate to:

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

Psoriatic Arthritis

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

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

Ankylosing Spondylitis (Bechterew's Disease)

Ankylosing spondylitis is an inflammatory disease of the spine. If you have ankylosing spondylitis, you will first be given other medications. If these medications do not work well enough, you will be given Remsima to:

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

Poriasis

Poriasis is an inflammatory disease of the skin. If you have plaque psoriasis, moderate to severe, you will first be given other medications or treatments such as phototherapy. If these medications or treatments do not work well enough, you will be given Remsima to reduce the symptoms and signs of your disease.

Ulcerative Colitis

Ulcerative colitis is an inflammatory disease of the intestine. If you have ulcerative colitis, you will first be given other medications. If these medications 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 medications. If these medications 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 skin, which have not been controlled by other medications or surgery.

You should not be given Remsima if:

• You are allergic to infliximab or 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 (serious bacterial infection of the blood),
• You have moderate to severe heart failure.

If any of the above applies to you, do not use Remsima. If you are unsure, consult your doctor before Remsima is administered to you.

Warnings and precautions

Consult your doctor before or during treatment with Remsima if:

You have previously received treatment with any medication containing infliximab

• Inform your doctor if you have received treatment with medications containing infliximab in the past and are now starting treatment with Remsima again.
• If you have stopped treatment with infliximab for more than 16 weeks, there is a higher risk of allergic reactions when starting treatment again.

Infections

• Inform your doctor before Remsima is administered if you have an infection, even a mild one.
• Inform your doctor before Remsima is administered if you have ever lived or traveled to an area where infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common. These infections are caused by specific types of fungi that can affect the lungs or other parts of your body.
• You may be more susceptible to infections while being treated with Remsima. If you are 65 or older, you are at higher risk.
• These infections can be serious and include tuberculosis, infections caused by viruses, fungi, bacteria, or other organisms in the environment, and septicemia, which can be potentially fatal.

Inform your doctor immediately if you notice signs of infection during treatment with Remsima, such as fever, cough, flu-like symptoms, general feeling of illness, redness or warmth on 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 had or has TB.
• Your doctor will perform 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 medications for TB. Your doctor will note these tests on your patient information card.
• If your doctor considers you to be at risk of TB, you may be treated with medications for TB before Remsima is administered.

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

Hepatitis B virus

• Inform your doctor before Remsima is administered if you are a carrier of hepatitis B or have had it in the past.
• Inform your doctor if you think you may be at risk of contracting hepatitis B.
• Your doctor should perform tests for the hepatitis B virus.
• Treatment with TNF blockers, such as Remsima, can cause reactivation of the hepatitis B virus in patients who are carriers of this virus, which in some cases can be potentially fatal.
• If you experience reactivation of hepatitis B, your doctor may need to stop your treatment, and you may be given effective antiviral therapy with supportive treatment.

Heart problems

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

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

Cancer and lymphoma

• Inform your doctor before Remsima is administered if you have or have had any type of cancer, including lymphoma (a type of blood cancer).
• Patients with severe rheumatoid arthritis, who have had the disease for a long time, may be at higher risk of developing lymphoma.
• Children and adults treated with Remsima may be at 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 boys or young men, and most had Crohn's disease or ulcerative colitis. This type of cancer is 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 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 old, may be recommended to have regular cervical cancer screenings.

Lung disease or heavy smokers

• Inform your doctor before Remsima is administered if you have a lung disease called chronic obstructive pulmonary disease (COPD) or if you are a heavy smoker.
• Patients with COPD and heavy smokers may be at higher risk of developing cancer during treatment with Remsima.

Nervous system disorders

• Inform your doctor before Remsima is administered if you have or have had any nervous system disorders. This includes multiple sclerosis, Guillain-Barré syndrome, if you have seizures or have been diagnosed with "optic neuritis."

Inform your doctor immediately if you notice symptoms of nervous system disorders during treatment with Remsima. The symptoms may include 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 Remsima is administered.

Vaccinations

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

Therapeutic infectious agents

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

Surgeries or dental procedures

• Inform your doctor if you are scheduled to have any surgery or 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 who received Remsima have developed severe liver problems.
• Inform your doctor immediately if you notice symptoms of liver problems during treatment with Remsima. The symptoms may include yellowing of the skin and eyes, dark brown urine, pain or swelling in the upper right abdomen, joint pain, skin rashes, or fever.

Low blood cell counts

• In some patients who receive Remsima, the body may not be able to produce enough blood cells that help fight infections or stop bleeding.
• Inform your doctor immediately if you notice symptoms of low blood cell counts during treatment with Remsima. The symptoms may include persistent fever, bleeding or bruising easily, small red or purple spots on the skin caused by bleeding under the skin, or paleness.

Immune system disorders

• Some patients who received Remsima have developed symptoms of an immune system disorder called lupus.
• Inform your doctor immediately if you develop symptoms of lupus during treatment with Remsima. The symptoms may include joint pain or a rash on the cheeks or arms caused by sensitivity to the sun.

Children and adolescents

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

• Some children and adolescents treated with TNF blockers, including infliximab, have developed cancers, even rare types, which in some cases have been fatal.
• More children treated with infliximab developed infections compared to adults.
• Children should receive recommended vaccinations before starting treatment with Remsima. Children may receive some vaccinations during treatment with Remsima, but they should not receive live vaccines while 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 at least 6 years old.

If you are unsure whether any of the above applies to you, consult your doctor before Remsima is administered to you.

Other medications and Remsima

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

Inform your doctor if you are taking, have taken recently, or may need to take any other medication, including any other medication for the treatment of Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis, or over-the-counter medications, such as vitamins or herbal supplements.

Particularly, inform your doctor if you are taking any of the following medications:

• Medications that affect your immune system.
• Kineret (which contains anakinra). Remsima and Kineret should not be used together.
• Orencia (which contains abatacept). Remsima and Orencia should not be used together.

You should not receive live vaccines while using Remsima. If you were using Remsima during pregnancy or are receiving Remsima during breastfeeding, inform your baby's doctor and other healthcare professionals about your treatment with Remsima before your baby is vaccinated.

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

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor before using this medication. Remsima should only be used during pregnancy or breastfeeding if your doctor considers it necessary for you.
• You should avoid becoming pregnant while being treated with Remsima and for 6 months after stopping treatment. Discuss using birth control measures during that time with your doctor.
• If you received Remsima during pregnancy, your baby may be at higher risk of contracting an infection.
• It is essential to inform your baby's doctors and other healthcare professionals about your treatment with Remsima before your baby is vaccinated. If you received Remsima while pregnant, the BCG vaccine (used to prevent tuberculosis) should not be given to your baby within 12 months of birth, as it can cause severe infection, including death. Live vaccines, such as the BCG vaccine, should not be given to your baby within 12 months of birth unless your baby's doctor recommends otherwise. For more information, see the section on vaccinations.
• If you are breastfeeding, it is essential to inform your baby's doctors and other healthcare professionals about your treatment with Remsima before your baby is vaccinated. Live vaccines should not be given to your baby while breastfeeding unless your baby's doctor recommends otherwise.
• In children born to mothers treated with infliximab during pregnancy, a severe decrease in white blood cell count in the blood 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 machines. If you feel tired, dizzy, or unwell after receiving Remsima, do not drive or use tools or machines.

Remsima contains sodium

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

Rheumatoid Arthritis

The usual dose is 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 Administered

• Remsima will be administered by your doctor or nurse.
• Your doctor or nurse will prepare the medication for infusion.
• The medication will be administered as an infusion (drip) (for 2 hours) in one of your veins, usually in your arm. After the third treatment, your doctor may decide to administer your Remsima dose for 1 hour.
• You will be monitored while Remsima is being administered and also during 1 to 2 hours afterwards.

How Much Remsima Will Be Administered

• Your doctor will decide your dose and how often Remsima will be administered. This will depend on your disease, weight, and how you respond to Remsima.
• The table below shows how often Remsima is normally administered 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 Too Much Remsima Is Administered

Since this medication is being administered by your doctor or nurse, it is unlikely that you will receive too much Remsima. The effects of an overdose of Remsima are unknown.

If You Miss a Remsima Infusion

If you miss or fail to attend a scheduled infusion of Remsima, schedule a new appointment as soon as possible. If you have any other questions about the use of this medication, consult your doctor.

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

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

• Signs of an allergic reactionsuch as swelling of the face, lips, mouth, or throat, which may cause difficulty swallowing or breathing, skin rash, urticaria, swelling of the hands, feet, or ankles. Some of these reactions can be severe or potentially life-threatening. An allergic reaction can occur within 2 hours of your injection or later. Other allergic side effects may occur up to 12 days after your injection, such as muscle pain, fever, joint pain or jaw pain, sore throat, or headache.
• Signs of a heart problemsuch as chest pain or discomfort, arm pain, stomach pain, difficulty breathing, anxiety, dizziness, lightheadedness, fainting, sweating, nausea (feeling sick), vomiting, palpitations or pounding in the chest, rapid or slow heart rate, 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 a burning sensation while urinating.
• Possible signs of cancerincluding, but not limited to, lymph node inflammation, weight loss, fever, rare skin nodules, changes in moles or skin color, or rare vaginal bleeding.
• Signs of a lung problemsuch as cough, difficulty breathing, or chest tightness.
• Signs of a nervous system problem (including eye problems)such as signs of a stroke (sudden numbness or weakness in the face, arm, or leg, especially on one side of the body; sudden confusion, difficulty speaking or understanding; sudden difficulty seeing in one or both eyes, sudden difficulty walking, dizziness, loss of balance or coordination, or severe headache), seizures, numbness or tingling in any part of the body, or weakness in the arms or legs, eye changes such as double vision or other eye problems.
• Signs of a liver problem(including hepatitis B infection, if you have had hepatitis B before) such as yellow skin and eyes, dark brown urine, upper right abdominal pain or swelling, joint pain, skin rash, or fever.
• Signs of an immune system disordersuch as joint pain or a sun-sensitive rash on 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 severe skin problemssuch as red, ring-shaped spots with central blisters on the trunk, large areas of skin that are flaking and raised (exfoliated), mouth, throat, nose, genital, or eye ulcers, or small, pus-filled bumps that can spread throughout the body. These skin reactions may be accompanied by fever.

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

The following side effects have been observed with 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
• Side effect due to infusion
• Pain.

Common:may affect up to 1 in 10 people

• Liver function changes, increased liver enzymes (shown in blood tests)
• Pulmonary or chest infections, such as bronchitis or pneumonia
• Difficulty breathing or painful breathing, chest pain
• Gastrointestinal bleeding, diarrhea, indigestion, heartburn, constipation
• Urticaria (hives), skin rash with itching or dry skin
• Balance problems or dizziness
• Fever, increased sweating
• Circulation problems such as low or high blood pressure
• Cardenals, shortness of breath, nasal bleeding, 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
• Lymph node inflammation
• Depression, sleep problems
• Eye problems, including red eyes and infections
• Fast heart rate (tachycardia) or palpitations
• Joint, muscle, or back pain
• Urinary tract infection
• Poriasis, skin problems such as eczema, and hair loss
• Reactions at the injection site such as pain, swelling, redness, or itching
• Chills, accumulation of fluid under the skin causing swelling
• Numbness or tingling.

Uncommon:may affect up to 1 in 100 people

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

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

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

Frequency not known:cannot be estimated from available data

• Cancer in children and adults
• A rare type of blood cancer that mainly affects teenage 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 as purple skin lesions
• Worsening of a disease called dermatomyositis (manifesting as 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 side effects in children and adolescents

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

Reporting of side effects

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

Remsima will be normally conserved by healthcare professionals. The conservation details, if needed, are as follows:

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the label and in the box after CAD. The expiration date is the last day of the month indicated.
• Store in the refrigerator (between 2°C – 8°C).
• This medication can also be stored in the original box outside the refrigerator for a maximum of 25°C for a single period of up to six months, but without exceeding the initial expiration date. In this situation, it should not be re-stored refrigerated. Write the new expiration date on the box including day/month/year. Dispose of this medication if it has not been used by the new expiration date or the expiration date printed on the box, whichever occurs first.
• It is recommended that when preparing Remsima for infusion, it should be used as soon as possible (within 3 hours). However, if the solution is prepared in germ-free conditions, it can be stored in the refrigerator between 2°C – 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 medication if there is alteration of the color or presence of particles.

Composition of Remsima

• The active ingredient is infliximab. Each vial contains 100 mg of infliximab. After preparation, each ml contains 10 mg of infliximab.
• The other components are sucrose, polisorbate 80, sodium dihydrogen phosphate monohydrate, and sodium hydrogen phosphate dihydrate.

Appearance of the product and contents of the container

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 tower

Hungary

Responsible Person

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

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Last review date of this leaflet: {MM/AAAA}

Other sources of information

Detailed information on this medicinal product 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 should be given the patient information leaflet.

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 not exceeding the initial expiry date. The new expiry date must be written on the box. Once removed from refrigerated storage, Remsima 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 commercial name and batch number of the medicinal product administered must be clearly recorded.

1. It is necessary to calculate the dose and the number of vials of Remsima. Each vial of Remsima contains 100 mg of infliximab. It is also necessary to calculate the total volume of the reconstituted Remsima solution required.

1. In aseptic conditions, each vial of Remsima 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 wool swab soaked in 70% alcohol. The syringe needle must be inserted into the vial in the center of the rubber stopper and the water for injections directed towards the glass wall of the vial. The solution must be gently removed by rotating the vial to dissolve the lyophilized powder. Agitation must be avoided. The vial must not be agitated. It is possible that foam may form in the solution during reconstitution. The reconstituted solution must be left to stand for 5 minutes. Check that the solution is colourless to pale yellow and opalescent. The solution may contain a few fine translucent particles, as infliximab is a protein. The solution must not be used if it contains opaque particles, colour change, or other foreign particles.

1. The volume of the reconstituted Remsima solution required must be diluted to 250 ml with infusion solution 9 mg/ml (0.9% sodium chloride). The reconstituted Remsima solution must not be diluted with any other diluent. The dilution may be carried out by extracting from the glass bottle or infusion bag of 250 ml a volume of infusion solution 9 mg/ml (0.9% sodium chloride) equal to the volume of Remsima reconstituted. The volume of the reconstituted Remsima solution required must be added slowly to the infusion bottle or bag of 250 ml and mixed gently. For volumes greater than 250 ml, use a larger infusion bag (e.g. 500 ml, 1,000 ml) or use several infusion bags of 250 ml to ensure that the concentration of the infusion solution does not exceed 4 mg/ml. If the reconstituted and diluted solution is stored refrigerated, it must be allowed to reach room temperature (25°C) for 3 hours before the infusion stage. Storage beyond 24 hours at 2°C-8°C applies only to the preparation of Remsima in the infusion bag.

1. The infusion solution must be administered for a period not less than the recommended infusion time (see section 3). Only one infusion set with a low-protein affinity, non-pyrogenic, and sterile (1.2 micrometre or smaller pore size) filter must be used. Since it does not contain preservatives, it is recommended that the administration of the infusion solution be initiated as soon as possible and within 3 hours of reconstitution and dilution. If not used immediately, the times and storage conditions before use are the responsibility of the user and are normally not more than 24 hours at 2°C – 8°C, unless the reconstitution/dilution was carried out in controlled and validated aseptic conditions. No unused portion of the infusion solution must be stored for re-use.

1. Before administration, Remsima must be visually inspected for particles or colour change. It must not be used if opaque particles, colour change, or foreign particles are observed.

1. The disposal of unused medicinal product and all materials that have been in contact with it must be carried out in accordance with local regulations.