Package Insert: Information for the User

Zessly 100 mg Powder for Concentrate for Solution for Infusion

infliximab

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

• Keep this package insert, 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 Zessly.
• If you have any questions, consult your doctor.
• This medicine has been prescribed to you alone, 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, pharmacist or nurse, even if they are not listed in this package insert. See section 4.

Zessly 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.

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

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

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

• Crohn's disease
• Ulcerative colitis.

Zessly 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 Zessly in combination with another medication called methotrexate to:

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 Zessly 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 Zessly to:

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 Zessly 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 Zessly 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 Zessly to:

You should not be given Zessly if:

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

Warnings and precautions

Consult your doctor before starting treatment with Zessly if:

You have previously received treatment with a medication containing infliximab

Infections

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

Tuberculosis (TB)

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

Hepatitis B virus

Heart problems

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

Cancer and lymphoma

Lung disease or heavy smokers

Neurological disorders

Inform your doctor immediately if you notice symptoms of neurological disease during treatment with Zessly. The symptoms may include changes in vision, weakness in your arms or legs, numbness or tingling in any part of your body.

Abnormal skin openings

Vaccinations

• Before starting treatment with Zessly, you should receive recommended vaccinations. You can receive some vaccinations during treatment with Zessly, but you should not receive live vaccines (vaccines that contain a weakened infectious agent) while using Zessly because they can cause infections.
• If you received Zessly 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 Zessly 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 Zessly 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 about to receive treatment with a therapeutic infectious agent (such as a BCG instillation used for cancer treatment).

Surgeries or dental procedures

Liver problems

• Some patients who received treatment with medications containing infliximab have developed severe liver problems.

Inform your doctor immediately if you notice symptoms of liver problems during treatment with Zessly. 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 treatment with medications containing infliximab, the body cannot 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 Zessly. The symptoms may include persistent fever, bleeding or easy bruising, or pale skin.

Immune system disorders

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

Inform your doctor immediately if you develop symptoms of lupus during treatment with Zessly. The symptoms may include joint pain or a rash on your cheeks or arms that is sensitive to the sun.

Children and adolescents

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

• 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 Zessly.

Children can receive some vaccinations during treatment with Zessly, but they should not receive live vaccines while using Zessly.

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

Other medications and Zessly

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

Inform your doctor if you are using or have recently used 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 using any of the following medications:

You should not receive live vaccines while using Zessly. If you were using Zessly during pregnancy or are receiving Zessly during breastfeeding, inform your baby's doctor and other healthcare professionals about your treatment with Zessly before your baby is vaccinated. For more information, see the section on pregnancy and breastfeeding.

If you are unsure about whether anything above applies to you, consult your doctor or pharmacist before using Zessly.

Pregnancy, breastfeeding, and fertility

Driving and using machines

It is unlikely that Zessly will affect your ability to drive or use tools or machines. If you feel tired, dizzy, or unwell after receiving Zessly, do not drive or use tools or machines.

Zessly contains sodium

Zessly contains less than 1 mmol of sodium (23 mg) per dose; that is, it is essentially "sodium-free." However, before Zessly is administered to you, it is mixed with a solution that contains sodium. Consult your doctor if you follow 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 Zessly will be administered

How much Zessly will be administered

Use in children and adolescents

Zessly 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 too much Zessly is administered

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

If you miss or forget a Zessly infusion

If you forget or miss a scheduled appointment to receive Zessly, 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 Zessly has ended.

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

• Signs of an allergic reactionsuch as swelling of your face, lips, mouth, or throat, which may cause difficulty swallowing or breathing, skin rash, urticaria, swelling of your hands, feet, or ankles. Some of these reactions may be severe or potentially life-threatening. An allergic reaction can occur within 2 hours of your injection or later. Additional signs of allergic reactions 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, sweating, nausea (feeling sick), vomiting, palpitations or pounding in your chest, rapid or slow heart rate, and swelling of your 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 your abdomen or around your 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 stroke symptoms (sudden numbness or weakness in your face, arm, or leg, especially on one side of your body; sudden confusion, difficulty speaking or understanding; difficulty seeing in one or both eyes, difficulty walking, dizziness, loss of balance or coordination, or severe headache), seizures, numbness or tingling in any part of your body, or weakness in your 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 your 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 your skin, or paleness.
  • Signs of severe skin problemssuch as red, ring-shaped spots with central blisters on your trunk, large areas of skin that are peeling and flaking, mouth, throat, nose, genital, or eye ulcers, or small, pus-filled bumps that can spread throughout your 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 medicines containing infliximab:

Very common(may affect more than 1 in 10 people)

Common(may affect up to 1 in 10 people)

Uncommon(may affect up to 1 in 100 people)

Rare(may affect up to 1 in 1,000 people)

Frequency not known(the frequency cannot be estimated from available data)

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 frequently in children were: low red blood cell count (anemia), blood in stool, low total white blood cell count (leucopenia), facial flushing (rubefaction), viral infections, low white blood cell count that fights infection (neutropenia), bone fracture, bacterial infection, 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 the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Zessly will generally be conserved by healthcare professionals. The conservation details if needed are as follows:

Composition of Zessly

Appearance of the product and contents of the pack

Zessly is presented in a glass vial containing a powder for concentrate for solution for infusion (powder for concentrate). The powder is white.

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

Marketing Authorization Holder

Sandoz GmbH

Biochemiestr. 10

6250 Kundl

Austria

Responsible Person for Manufacturing

Sandoz GmbH

Biochemiestr. 10

6336 Langkampfen

Austria

Lek Pharmaceuticals d.d.

Verovškova ulica 57

1526 Ljubljana

Slovenia

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

The 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 infliximab should be given the patient information leaflet.

Instructions for use and handling – storage conditions

Store at 2 °C-8 °C.

Zessly can be stored at temperatures of up to a maximum of 30 °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, Zessly 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. Calculate the dose and the number of vials of Zessly required. Each vial of Zessly contains 100 mg of infliximab. Calculate the total volume of reconstituted Zessly solution required.

1. In aseptic conditions, reconstitute each vial of Zessly with 10 ml of water for injections, using a syringe equipped with a 21-gauge (0.8 mm) or smaller needle. Remove the vial cap and clean the top with a cotton wool swab soaked in 70% alcohol. Insert the syringe needle into the vial in the center of the rubber stopper and direct the water for injections towards the glass wall of the vial. Gently remove the solution by rotating the vial to dissolve the lyophilized powder. Avoid prolonged or vigorous agitation. DO NOT AGITATE. It is not uncommon for foam to form in the solution during reconstitution. Allow the reconstituted solution to stand for 5 minutes. Check that the solution is colourless to light brown and opalescent. The solution may contain a few fine translucent particles, as infliximab is a protein. Do not use if the solution contains opaque particles, colour change, or other foreign particles.

1. Dilute the total dose volume of reconstituted Zessly solution to 250 ml with 9 mg/ml (0.9%) sodium chloride solution for injection. Do not dilute the reconstituted Zessly solution with any other diluent. The dilution can be performed by extracting from the glass bottle or infusion bag of 250 ml a volume of 9 mg/ml (0.9%) sodium chloride solution for injection equal to the volume of reconstituted Zessly. Add the total volume of reconstituted Zessly solution slowly to the infusion bottle or bag. Mix gently.

1. Administer the infusion solution over a period not less than the recommended infusion time. Use only a single infusion set with a low-protein affinity, non-pyrogenic, and sterile (1.2 micrometre or smaller pore size) filter. 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. When reconstitution and dilution are performed under aseptic conditions, the Zessly infusion solution can be used within 24 hours if stored between 2 °C and 8 °C. Do not store any unused portion of infusion solution for re-use.

1. No compatibility studies have been performed to evaluate the concomitant administration of Zessly with other agents. Do not infuse Zessly concomitantly with other agents in the same intravenous line.

1. Before administration, visually inspect Zessly for particles or colour change. Do not use if visible 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 shall be in accordance with local requirements.