Package Insert: Information for the User

Inflectra100mg Powder for Concentrate for Solution for Infusion

infliximab

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• Your doctor will give you a patient information leaflet, which contains important safety information you need to know before and during your treatment with Inflectra.
• When starting a new leaflet, keep this leaflet as a reference for 4months after your last dose of Inflectra.

• If you have any questions, consult your doctor.

• This medication has been prescribed to you alone, and you should not give it to others 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 are not listed in this package insert.See section 4.

Inflectra contains the active ingredient infliximab, which is of human and mouse origin. Infliximab is a monoclonal antibody, a type of protein that binds to a specific target in the body called TNF (tumor necrosis factor) alpha.

Inflectra 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.

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

• Crohn's disease
• Ulcerative colitis.

Inflectra acts by selectively binding to TNF alpha (tumor necrosis factor alpha) and blocking its action. TNF alpha is involved in the body's inflammatory process, and blocking it may 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 Inflectra in combination 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 Inflectra to:

• Reduce the symptoms and signs of your disease,
• Decrease 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 Inflectra 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 moderate to severe plaque psoriasis, you will first be given other medications or other treatments such as phototherapy. If these medications or treatments do not work well enough, you will be given Inflectra 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 Inflectra 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 Inflectra 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 receive Inflectra if:

• You are allergic to infliximab or any of the other components of this medication (listed in section6),

• You are allergic (hypersensitive) to proteins derived from mice,
• You have tuberculosis (TB) or another serious infection such as pneumonia or septicemia (severe bacterial infection of the blood),
• You have moderate to severe heart failure.

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

Warnings and precautions

Consult your doctor before or during treatment with Inflectra if:

You have 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 Inflectra again.

• If you interrupt treatment with infliximab for more than 16weeks, there is a higher risk of allergic reactions when you start treatment again.

Infections

• Inform your doctor if you have an infection, even a mild one, before Inflectra is administered to you.
• Inform your doctor if you have lived or traveled to an area where infections such as histoplasmosis, coccidioidomycosis, or blastomycosis are common before Inflectra is administered to you. These infections are caused by specific types of fungi and can affect the lungs or other parts of your body.
• You may be more susceptible to infections when being treated with Inflectra. 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 life-threatening.

• Inform your doctor immediately if you experience signs of infection during treatment with Inflectra, such as fever, cough, flu-like symptoms, general feeling of illness, redness or warmth on the skin, wounds, or dental problems. Your doctor may temporarily suspend treatment with Inflectra.

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, and even in patients who have already been treated with medications for TB. Your doctor will record the results of these tests on your patient information card.
• If your doctor considers you to be at risk of TB, you will need to be treated with medications for TB before Inflectra is administered to you.

• Inform your doctor immediately if you experience symptoms of TB during treatment with Inflectra. The symptoms are persistent cough, weight loss, fatigue, fever, and night sweats.

Hepatitis B virus

• Inform your doctor if you are a carrier or have ever had hepatitis B before Inflectra is administered to you.
• Inform your doctor if you think you may be at risk of contracting hepatitisB.
• Your doctor should perform tests for the hepatitisBvirus.
• Treatment with TNF blockers such as Inflectra can cause reactivation of the hepatitis B virus in people who are carriers of this virus, which in some cases can be life-threatening.
• If you experience reactivation of hepatitisB, your doctor may need to interrupt 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 experience new symptoms or worsening of heart failure during treatment with Inflectra. The symptoms include difficulty breathing or swelling of the feet.

Cancer and lymphoma

• Inform your doctor if you have or have had lymphoma (a type of blood cancer) or any other type of cancer before Inflectra is administered to you.
• 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 Inflectra may be at higher risk of developing lymphoma or other types of cancer.
• Some patients who have receivedTNF blockers, includinginfliximab have developed a rare type of cancer called hepatosplenic T-cell lymphoma. Most of these patients were male adolescents or young adultsand most had Crohn's disease or ulcerative colitis. This type of cancer is usually fatal. Almost all of these patients had also received medications such as 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 experience any changes in the appearance of your skin or abnormal skin growth during or after treatment.
• Some women treated with infliximab for rheumatoid arthritis have developed cervical cancer. Women treated with Inflectra, even those over 60years old, may be recommended to have regular cervical cancer screenings.

Lung disease or heavy smokers

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

Neurological disorders

• Inform your doctor if you have or have had any neurological disorder before Inflectra is administered to you. This includes multiple sclerosis, Guillain-Barré syndrome, if you have seizures or have been diagnosed with “optic neuritis”.

Inform your doctor immediately if you experience symptoms of neurological disorders during treatment with Inflectra. 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

• Inform your doctor if you have any abnormal skin ulcers (fistulas) before Inflectra is administered to you.

Vaccinations

• Inform your doctor if you have recently had or are scheduled to receive a vaccination.
• Before starting treatment with Inflectra, you should receive recommended vaccinations. You may receive some vaccinations during treatment with Inflectra, but you should not receive live vaccines(vaccines that contain a weakened live agent)while using Inflectrabecause they may cause infections.

• If you received treatment with Inflectra during pregnancy, your baby may also be at higher risk of contracting the infection as a result of receiving a live vaccine during the first year of life. It is essential to inform pediatricians and other healthcare professionals about your treatment with Inflectra 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 pediatricians and other healthcare professionals about your treatment withInflectrabefore 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 will receive treatment with therapeutic infectious agents (such as a BCG instillation used for cancer treatment)

Surgeries or dental interventions

• Inform your doctor if you are scheduled to have any dental intervention or surgery.
• Inform your surgeon or dentist that you are being treated with Inflectra by showing them your patient information card.

Liver problems

• Some patients who received infliximab have developed severe liver problems.
• Inform your doctor immediately if you experience symptoms of liver problems during treatment with Inflectra. 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 receiving infliximab, the body cannot produce enough blood cells that help fight infections or stop bleeding.
• Inform your doctor immediately if you experience symptoms of low blood cell counts during treatment with Inflectra. The symptoms may include persistent fever, bleeding, or easy bruising, small red or purple spots caused by bleeding under the skin, or paleness.

Immune system disorders

• Some patients who received infliximab have developed symptoms of an immune system disorder called lupus.
• Inform your doctor immediately if you experience symptoms of lupus during treatment with Inflectra. 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 like infliximab have developed cancers, some of which are rare, that 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 Inflectra. Children may receive some vaccinations during treatment with Inflectra, but they should not receive live vaccines while using Inflectra.

Inflectra should only be used in children if they are being treated for Crohn's disease or ulcerative colitis. These children must be at least 6years old.

If you are unsure whether anything above applies to you, consult your doctor before Inflectra is administered to you.

Other medications and Inflectra

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

Inform your doctor if you are taking, have taken recentlyor may need to takeany 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.

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

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

You should not receive live vaccines while using Inflectra. If you were using Inflectra during pregnancyor if you are receivingInflectraduring breastfeeding, inform your pediatrician and other healthcare professionals caring for your baby about your treatment with Inflectra before your baby receives any vaccine.

If you are unsure whether anything above applies to you, consult your doctor or pharmacist before starting to use Inflectra.

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 medication. Inflectra 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 Inflectra and for 6months after completing treatment. Discuss contraceptive measures with your doctor during that time.
• If you received treatment with Inflectra during pregnancy, your baby may be at higher risk of contracting an infection.
• It is essential to inform pediatricians and other healthcare professionals about your treatment with Inflectra before vaccinating your baby.If you received Inflectra during pregnancy, the administration of the BCG vaccine (used to prevent tuberculosis) to your baby within 12months after birth may cause infections with severe complications, including death. Live vaccines, such as the BCG vaccine, should not be administered to your baby within 12months after birth, unless your pediatrician recommends otherwise.For more information, see the section on vaccinations.
• Ifyou are breastfeeding, it is essential to inform pediatricians and other healthcare professionals about your treatment with Inflectra before your baby is vaccinated.Live vaccines should not be administered to your baby while breastfeeding, unless your pediatrician 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 experiences fever or persistent infections, contact your pediatrician immediately.

Driving and operating machinery

It is unlikely that Inflectra will affect your ability to drive and operate machinery. If you feel tired, dizzy, or unwell after receiving Inflectra, do not drive or operate machinery.

Inflectra contains sodium

Inflectra contains less than 1mmol of sodium (23mg) per dose; this is, essentially “sodium-free.” However, before Inflectra is administered to you, it is mixed with a solution that contains sodium. Inform your doctor if you are following a low-sodium diet.

How much Inflectra will be administered

• The doctor will decide your dose and how often you will receive Inflectra. This will depend on your disease, weight, and how you respond to Inflectra.
• The following table shows how often you will normally receive this medication after your first dose.

Rheumatoid Arthritis

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

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

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

How Inflectra will be administered

• Inflectra will be administered by your doctor or nurse, in a hospital or clinic.
• Your doctor or nurse will prepare the medication for infusion.
• The medication will be administered as an intravenous infusion (drip) (for 2 hours) in one of the veins, usually in the arm.After the third treatment, your doctor will decide if you will receive the Inflectra dose for 1 hour.
• You will be monitored while you receive Inflectra and also during 1 to 2 hours afterwards.

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 Inflectra is administered

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

Missed dose or failure to attend Inflectra infusion

If you forget or fail to attend a scheduled appointment to receive Inflectra, schedule a new appointment as soon as possible.

If you have any other questions about the use of this medication, ask 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 require treatment. Side effects can occur after your treatment with Inflectra has ended.

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

• Allergic reactionssuch as swelling of the face, lips, mouth, or throat, which may cause difficulty swallowing or breathing, skin rash, urticaria, swelling in the hands, feet, or ankles. Some of these reactions can be severe or potentially life-threatening. The allergic reaction can occur within 2hours after infusion or later. Additional signs of allergic reactions may occur up to 12días after infusion, such as muscle pain, fever, joint pain or jaw pain, sore throat, or headache.

• Heart problemssuch as chest discomfort or pain, arm pain, stomach pain, difficulty breathing, anxiety, dizziness, fainting, sweating, nausea (feeling unwell), vomiting, palpitations or chest tightness, rapid or slow heart rate, and swelling of the feet.
• Infections (including TB)such as fever, fatigue, persistent cough, difficulty breathing, flu-like symptoms, weight loss, night sweats, diarrhea, wounds, abscesses in the abdomen or around the anus, dental problems, or 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.

• Lung problemssuch as cough, difficulty breathing, or chest tightness.
• Neurological problems (including eye problems)such as stroke symptoms (sudden numbness or weakness in the face, arms, or legs, especially on one side of the body; sudden confusion, difficulty speaking or understanding; 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.
• Liver problems(including hepatitis B infection, when you have had hepatitis B previously) such as yellow skin or eyes, dark brown urine, upper right abdominal pain or swelling, joint pain, skin rash, or fever.
• Immune system diseasessuch as joint pain, sun-sensitive rash on the cheeks or arms (lupus), or cough, difficulty breathing, fever, or skin rash (sarcoidosis).
• Low blood cell countssuch as persistent fever, bleeding, or bruising easily, small red or purple spots caused by bleeding under the skin, or paleness.
• Severe skin problemssuch as circular, red patches with central blisters on the trunk, large areas of skin that are peeled and raised, 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.

Consult your doctor immediately if you observe any of the above.

The following side effects have been observed withInflectra:

Very common: may affect more than 1in 10people

• 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 1in 10people

• Liver function changes, increased liver enzymes (shown in blood tests).
• Pneumonia or chest infections, such as bronchitis or pneumonia.
• Difficulty or pain breathing, chest pain.
• Gastrointestinal bleeding, diarrhea, indigestion, heartburn, constipation.
• Rash (urticaria), skin rash with itching or dry skin.
• Balance problems or dizziness.
• Fever, increased sweating.
• Circulation problems such as low or high blood pressure.
• Cardinal signs, shortness of breath, or nasal bleeding, heat, skin redness (flushing).
• 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 disturbances.
• Eye problems that include 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, fluid accumulation under the skin causing swelling.
• Feeling numb or tingling.

Uncommon: may affect up to 1in 100people

• Poor blood circulation, swelling of a vein.
• Blood accumulation outside of blood vessels(hematoma) or cardinal signs.
• Skin problems such as vesicles, warts, abnormal skin color or pigmentation, swollen lips, skin thickening, or red, scaly, and peeling skin.
• Severe allergic reactions (e.g., anaphylaxis), autoimmune disease 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 that include blurred or reduced vision, swollen or puffy eyes.
• Heart problems or worsening of the same, decreased heart rate.
• Fainting.
• Seizures, nerve problems.
• Intestinal ulcer or intestinal obstruction, stomach pain or cramps.
• Pancreatitis.
• Fungal infections such as Candida infection or fungal nail infection.
• Pulmonary problems (such as edema).
• Pleural effusion.

• Respiratory tract narrowing in the lungs, causing difficulty breathing.
• Pleurisy, which causes severe chest pain that worsens with breathing(pleurisy).
• Tuberculosis.

• Renal infections.
• Low platelet count, too many white blood cells in the blood.
• Vaginal infections.
• Abnormal blood test results showing "antibodies" against your own body.
• Changesin cholesterol and fat levels in the blood.
• Weight gain (for most patients, weight gain was small).

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

• A type of blood cancer (lymphoma).
• Insufficient oxygen supply to the body, circulation problems such as vein narrowing.
• Meningitis, inflammation of the membranes that protect the brain.
• Infections due to a weakened immune system.
• Hepatitis B infection, when you have had it previously.
• Liver inflammation caused by an immune system problem (autoimmune hepatitis).
• Jaundice, a condition that causes yellow skin and eyes.
• 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 may affect the lungs, skin, and lymph nodes (e.g., sarcoidosis).

• Granulomatous lesions, which are accumulations of immune cells as a result of an inflammatory response.

• 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.

• Severe neurological problems such as transverse myelitis, multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.

• Inflammation in the eye that can cause vision changes, including blindness.

• Pleural effusion.

• Severe heart problems (such as pulmonary embolism).

• Myocardial infarction.

• Stroke.

• Temporary loss of vision during or after two hours of infusion.

• Infection due to a weakened immune system caused by a live vaccine.

Other side effects in children and adolescents

Children who took infliximab for Crohn's disease showed some differences in side effects compared to adults who took infliximab for Crohn's disease. The side effects that occurred more often in children were: anemia, blood in stool, low white blood cell count, facial flushing, viral infections, low white blood cell count that fights infection, fractures, bacterial infections, and allergic reactions in the respiratory tract.

Reporting side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Inflectra will be normally stored by healthcare professionals in a hospital or clinic. The storage 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 a refrigerator (between 2°C and 8°C).
• This medication can also be stored in the original container outside the refrigerator up to 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. Discard 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 Inflectra for infusion, it should be used as soon as possible (within 3 hours). However, if the solution is prepared in a germ-free environment, it can be stored in a refrigerator between 2 °C and 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 a change in color or presence of foreign particles.

Composition of Inflectra

• 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, dihydrogen phosphate monohydrate and sodium dihydrogen phosphate dihydrate.

Appearance of the product and contents of the container

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

Inflectra is available in containers with 1, 2, 3, 4 or 5 vials. Not all container sizes may be marketed.

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Responsible for manufacturing

Hospira Zagreb d.o.o.

Prudnicka cesta 60

10291 Prigorje Brdovecko

Croatia

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Spain

Pfizer, S.L.

Tel: + 34 91 490 99 00

Last review date of this leaflet

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

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This information is intended solely for healthcare professionals:

Patients treated with Inflectra should be given the patient information leaflet.

Instructions for use and handling – storage conditions

Store between 2 °C and 8 °C.

Inflectra can be stored at temperatures of up to a maximum of 25 °C for a single period of up to 6 months, but not exceeding the initial expiration date. The new expiration date must be written on the box. Once removed from refrigerated storage, Inflectra should not be returned to refrigerated storage.

Instructions for use and handling: reconstitution, dilution and administration

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

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

2. In aseptic conditions, each vial of Inflectra must be reconstituted with 10 ml of water for injections, using a syringe equipped with a 21 G (0.8 mm) or smaller needle. The removable stopper of the vial must be removed and the top cleaned with an alcohol-soaked cotton swab. 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 powder. Prolonged or vigorous agitation must be avoided. THE VIAL MUST NOT BE AGITATED. It is possible that during reconstitution, foam may form in the solution. The reconstituted solution must be left to stand for 5 minutes. The solution must be colorless to light yellow and opalescent. In the solution, fine translucent particles may appear, as infliximab is a protein. The solution must not be used if it presents opaque particles, color alteration or other foreign particles.

3. The volume of reconstituted Inflectra solution required must be diluted to 250 ml with infusion solution 9 mg/ml (0.9%) of sodium chloride. The reconstituted Inflectra solution must not be diluted with any other diluent.This dilution can be performed by extracting from the glass bottle or infusion bag of 250 ml a volume of infusion solution 9 mg/ml (0.9%) of sodium chloride equal to the volume of reconstituted Inflectra. The volume of reconstituted Inflectra solution required must be added slowly to the bottle or infusion 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 after reconstitution and dilution it is stored refrigerated, the infusion solution must be left to reach room temperature at 25 °C for 3 hours before the Stage 4 (infusion). Storage beyond 24 hours at 2 °C – 8 °C only applies to the preparation of Inflectra in the infusion bag.

4. The intravenous 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 (pore size 1.2 micrometers or smaller) filter must be used. As it does not contain preservatives, it is recommended that the administration of the intravenous infusion solution be started 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 normally should not exceed 24 hours between 2 °C and 8 °C, unless the reconstitution / dilution has been performed in controlled and validated aseptic conditions. Unused portions of intravenous infusion solution must not be stored for reuse.

5. Before administration, Inflectra must be visually inspected for particles or color alteration. It must not be used if opaque particles are visible, color alteration or foreign particles are observed.

6. The disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations.