Prospect: information for the user

Ilaris 150mg/ml injectable solution

canakinumab

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect. See section4.

1.What is Ilaris and for what it is used

2.What you need to know before starting to use Ilaris

3.How to use Ilaris

4.Possible adverse effects

5.Storage of Ilaris

6.Contents of the package and additional information

What is Ilaris

Ilaris contains the active ingredient canakinumab, a monoclonal antibody that belongs to a group of medicines called interleukin inhibitors. In the body, it blocks the activity of a substance called interleukin-1 beta (IL-1 beta), which is present at high levels in inflammatory diseases.

What is Ilaris used for

Ilaris is used to treat the following inflammatory diseases:

• Periodic fever syndromes:

• Periodic syndromes associated with cryopyrin (CAPS*),
• Periodic syndrome associated with tumor necrosis factor receptor (TRAPS*),
• Hyperimmunoglobulin D syndrome (HIDS*)/mevalonate kinase deficiency (MKD*),
• Familial Mediterranean fever (FMF).

• Still's disease including adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA)
• Gouty arthritis

(*) by its English acronym

The following includes more information about these diseases.

Periodic fever syndromes

Ilaris is used in adults and children aged 2 years and older to treat the following diseases:

• Periodic syndromes associated with cryopyrin (CAPS) – a group of autoimmune inflammatory diseases, which includes:

• Muckle-Wells syndrome (MWS),
• Neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic cutaneous and articular (CINCA) syndrome,
• Severe manifestations of familial cold autoinflammatory syndrome (FCAS) / familial cold urticaria (FCU) that presents with signs and symptoms beyond the skin eruption induced by cold.

• Periodic syndrome associated with tumor necrosis factor receptor (TRAPS)
• Hyperimmunoglobulin D syndrome (HIDS)/mevalonate kinase deficiency (MKD)
• Familial Mediterranean fever (FMF): Ilaris is used to treat FMF. Ilaris can be used in combination with colchicine, if appropriate.

In patients with periodic fever syndromes (CAPS, TRAPS, HIDS/MKD, and FMF), the body produces too much IL-1 beta. This can cause fever, headache, fatigue, skin rash, or joint and muscle pain. By blocking the activity of IL-1 beta, Ilaris can improve these symptoms.

Still's disease

Ilaris is used in adult, adolescent, and children aged 2 years and older to treat active Still's disease including adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (sJIA) when other treatments have not worked well. Ilaris can be used alone or in combination with methotrexate.

Still's disease that includes AOSD and sJIA is an inflammatory disease that can cause pain, swelling, and inflammation of one or more joints, as well as rash and fever. The pro-inflammatory protein IL-1beta plays an important role in the inflammation of Still's disease. Ilaris can improve the signs and symptoms of Still's disease by blocking the activity of IL-1beta.

Gouty arthritis

Ilaris is used in adults to treat the symptoms of frequent gouty arthritis attacks if other treatments have not worked well enough.

Gouty arthritis is caused by the formation of urate crystals. These urate crystals cause an excessive production of IL-1 beta, which in turn can cause a sudden severe pain, redness, heat, and swelling of the joints (known as a gout attack). By blocking IL-1 beta, Ilaris can improve these symptoms.

No use Ilaris

-if you are allergic to canakinumab or any of the other components of this medication (listed in section 6).

-if you have, or suspect that you have, a severe and active infection.

Warnings and precautions

Consult your doctor before starting to use Ilaris,if you are in any of the following situations:

• if you have any infection currently or if you have had repeated infections or suffer from any disease such as low white blood cell count that makes you more vulnerable to infections.
• if you have or have ever had tuberculosis or direct contact with a person with an active tuberculosis infection. Your doctor may check if you have tuberculosis using a specific test.
• if you have signs of liver disorder such as yellow discoloration of the skin and eyes, nausea, loss of appetite, dark urine, and pale stools.
• if you need to get vaccinated. It is recommended to avoid being vaccinated with a type of vaccine (also known as attenuated vaccine) while using Ilaris (see also "Use of Ilaris with other medications).

Consult your doctor immediately

-if you have ever presented a generalized atypical rash or skin peeling after taking Ilaris.

Rarely, a severe skin reaction, DRESS (drug reaction with eosinophilia and systemic symptoms), has been reported associated with Ilaris treatment, especially in patients with systemic juvenile idiopathic arthritis (AIJs). Seek medical attention immediately if you observe a generalized atypical rash, which may appear along with high fever and lymph node enlargement.

Still's disease

• Patients with Still's disease may develop a condition called macrophage activation syndrome (MAS) that can cause death. Your doctor will monitor possible triggers of MAS, which include infections and re-activation of Still's disease (worsening).

Children and adolescents

• CAPS, TRAPS, HIDS/MKD, FMFand AIJS:Ilaris can be used in children from 2years of age.
• Gouty arthritis:Ilaris is not recommended for children or adolescents under 18years of age.

Other medications and Ilaris

Inform your doctor, pharmacist, or nurse if you are using, have used recently, or may need to use any other medication.

• Attenuated vaccines: It is recommended to avoid being vaccinated with a type of vaccine known as attenuated vaccine while on treatment with Ilaris. Your doctor may need to check your vaccination history and give you those vaccines that you have not received before starting treatment with Ilaris. If necessary, administer an attenuated vaccine 3months after your last Ilaris injection and 3months before the next.
• Medications known as tumor necrosis factor (TNF) inhibitors, such as etanercept, adalimumab, or infliximab. These are used mainly in rheumatic and autoimmune diseases. They should not be used with Ilaris because it may increase the risk of infections.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

• You should avoid becoming pregnant and it is recommended to use adequate contraceptive measures while taking Ilaris and for at least three months after the last administration. It is essential to inform your doctor if you are pregnant, if you may be pregnant, or if you are planning to have a baby. Your doctor will inform you about the potential risk of using Ilaris during pregnancy.
• If you receive canakinumab while pregnant, it is essential to inform the pediatrician or nurse before administering any vaccine to your baby. Your baby should not receive live vaccines until at least 16weeks after you have received your last dose of canakinumab before delivery.
• The passage of Ilaris into breast milk is unknown. Your doctor will inform you about the potential risks of using Ilaris before breastfeeding.

Driving and operating machinery

Treatment with Ilaris may cause asensation of dizziness (dizziness or vertigo) or intense fatigue (asthenia). This may affect your ability to drive or use tools or machines. If you experience dizziness or feel tired, do not drive or use tools or machines until you feel better.

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

Inform your doctor about your disease and any symptoms before using or that are administered Ilaris (see section2). Your doctor may decide to postpone or interrupt your treatment, only when necessary.

Ilaris must be used subcutaneously. This means it is injected with a short needle into the fatty tissue under the skin.

If you have gouty arthritis, a specialist doctor will supervise your treatment. Ilaris should only be injected by a healthcare professional.

If you have CAPS,TRAPS, HIDS/MKD, FMFor Still's disease (ESA or AIJS), you can inject yourself with Ilaris after receiving proper training, or have a caregiver inject it for you.

How much Ilaris to use

Periodic syndromes associated with cryopyrin (CAPS)

The recommended initial dose of Ilaris is:

• Adults and children 4years or older

• 150mg for patients weighing more than40kg
• 2mg/kg for patients weighing between15kgy40kg
• 4mg/kg for patients weighing between 7.5kg and less than15kg

• Children 2 or 3years old

• 4mg/kg for patients with a body weight of 7.5kg or more

Ilaris is injected every 8weeks as a single injection.

• If you do not respond sufficiently to treatment within 7days, your doctor may give you another dose of 150mg or 2mg/kg.
• If you respond sufficiently to the second dose, your treatment will continue with 300mg or 4mg/kg every 8weeks.
• If you do not respond sufficiently to the second dose, a third dose of Ilaris may be administered at 300mg or 4mg/kg.
• If you respond sufficiently to the third dose, your treatment will continue with 600mg or 8mg/kg every 8weeks.

In children who started with an initial dose of 4mg/kg and did not respond sufficiently after 7days, the doctor may give another dose of 4mg/kg. If the child responds sufficiently to this, treatment may be continued with a dose of 8mg/kg every 8weeks.

Periodic syndrome associated with tumor necrosis factor receptor (TRAPS), HIDS/deficiency of mevalonate kinase (MKD) and Familial Mediterranean fever (FMF)

The recommended initial dose of Ilaris is:

• Adults and children 2years or older

• 150mg for patients weighing more than40kg
• 2mg/kg for patients weighing between 7.5kg and less than 40kg

Ilaris is injected every 4weeks as a single injection.

• If you do not respond sufficiently to treatment within 7days, your doctor may give you another dose of 150mg or 2mg/kg.
• If you respond sufficiently to this, your treatment will continue with 300mg or 4mg/kg every 4weeks.

Still's disease (AIJS and ESA)

The recommended dose of Ilaris for patients with Still's disease weighing 7.5kg or more is 4mg/kg (up to a maximum of 300mg). Ilaris is injected every 4weeks as a single dose.

Gouty arthritis

Your doctor will discuss with you the need to start or adjust urate-lowering treatment to reduce your blood uric acid level.

The recommended dose for Ilaris in adult patients with gout is 150mg administered as a single dose during a gouty arthritis attack.

If you need another treatment with Ilaris, and with the last dose you obtained relief, you must wait at least 12weeks before a subsequent dose.

Self-injection of Ilaris or injection of Ilaris to a patient

If you are a patient with CAPS,TRAPS, HIDS/MKD, FMFor Still's disease (ESA or AIJS), or a caregiver of a patient with one of these diseases, you can administer the Ilaris injectionsafter receiving proper training on the injection technique.

• The patient or caregiver and the doctor will decide who will administer the Ilaris injections.

• Your doctor or nurse will teach you how to administer the Ilaris injections.

• Do not try to administer an injection if you have not received the necessary training or are unsure of how to do it.
• Ilaris 150mg/ml injectable solution is supplied in a single-use vial for individual use.
• Do not reuse the remaining solution.

For more information on how to administer Ilaris injections, see the "Instructions for use"section at the end of this leaflet. If you have any doubts, consult your doctor, pharmacist, or nurse.

Duration of treatment with Ilaris

• CAPS,TRAPS, HIDS/MKD, FMFor Still's disease (ESA or AIJS):you should continue using Ilaris for the time your doctor advises.
• Gouty arthritis:if you have a gouty arthritis attack, you will be given a single dose of Ilaris. If you experience another attack, your doctor may consider administering another dose of Ilaris but not before 12weeks of the previous dose.

Using more Ilaris than you should

If you accidentally inject more Ilaris than the recommended dose, it is unlikely to be serious but you should inform your doctor, pharmacist, or nurse as soon as possible.

Missing a dose of Ilaris

If you have CAPS,TRAPS, HIDS/MKD or FMForStill's disease (ESA orAIJS) andhave forgotten to inject a dose of Ilaris, the next dose should be injected as soon as you remember. Then, discuss with your doctor to agree on when to inject the next dose. You should then continue with the injection at the recommended intervals as before.

Stopping treatment with Ilaris

Stopping your treatment with Ilaris may cause a worsening of your disease. Do not stop treatment with Ilaris unless your doctor tells you to.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Some side effects can be serious. Inform your doctor immediately if you experience any of the following side effects:

• Prolonged fever for more than 3 days or any symptom that may suggest a severe infection. This includes chills, shivering, general feeling of illness, loss of appetite, body aches, usually related to the sudden onset of the disease, sore throat or mouth ulcers, cough, phlegm, chest pain, difficulty breathing, ear pain, prolonged headache, and localized redness, heat, and swelling of the skin or inflammation of connective tissue (cellulitis). These symptoms may be due to a severe infection, an unusual infection (opportunistic infection) or be related to low white blood cell counts (leukopenia and neutropenia). If necessary, your doctor may perform regular blood tests.

• Allergic reactions with itching and hives and possibly also difficulty breathing or swallowing, dizziness, unusual awareness of heartbeats (palpitations), and low blood pressure.

Other side effects of Ilaris include:

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

• Any type of infection. These may include:

• Respiratory infections such as pneumonia, bronchitis, flu-like symptoms, sinusitis, rhinitis, pharyngitis, tonsillitis (sore throat), nasopharyngitis, and upper respiratory tract infections.
• Other infections such as ear infection, skin infection (cellulitis), stomach pain, and gastroenteritis, and pain and frequent need to urinate with or without fever (urinary tract infection).

• Upper abdominal pain.
• Joint pain (arthralgia).
• Decreased white blood cell counts (leukopenia).
• Abnormal kidney function results (decreased renal clearance, proteinuria).
• Reactions at the injection site (such as redness, swelling, heat, and itching).

Common(may affect up to 1 in 10people):

• Candida – vaginal yeast infection (vulvovaginal candidiasis).
• Feeling dizzy, sensation of spinning (dizziness or vertigo).
• Back or muscle pain.
• Sensation of weakness or feeling very tired (fatigue, asthenia).
• Decreased white blood cell counts that help prevent infection (neutropenia).
• Abnormal triglyceride levels in your blood (lipid metabolism disorder).
• Abnormal liver function test results (elevated transaminases) or high bilirubin levels in the blood, with or without yellowing of the skin and eyes (hyperbilirubinemia).

Rare(may affect up to 1 in100people):

• Heartburn (gastroesophageal reflux disease).
• Decreased platelet counts that help prevent bleeding (thrombocytopenia).

Inform your doctor or your child's doctor immediately if you notice any of these symptoms.

Reporting 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 notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

• 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 the box. The expiration date is the last day of the month indicated.

• Store in refrigerator (between 2°C and 8°C). Do not freeze.

• Keep the vial in the case to protect it from light.

• The solution must be used immediately after the first puncture of the vial cap to prepare the injection.

• Do not use this medication if you notice that the solution is not transparent to opalescent or contains particles.

• All unused medication must be discarded after injecting the dose.

Medications should not be thrown down the drain or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Ilaris

• The active ingredient is canakinumab. A vial contains 150mg of canakinumab in 1ml of solution.

• The other components aremanitol, histidina, histidina hidrocloruro monohidrato, polisorbato 80, agua para preparaciones inyectables.

Appearance of the product and contents of the package

• Ilaris is presented in the form of an injectable solution inside a 2ml glass vial.
• The solution is a transparent to opalescent and colorless to slightly yellowish liquid. Do not use it if the liquid contains easily visible particles, is turbid or a brown color is appreciated.

• Ilaris is available in boxes containing one vial.

Marketing Authorization Holder

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Irlanda

Responsible for manufacturing

Novartis Farmacéutica, S.A.

Gran Vía de les Corts Catalanes, 764

08013 Barcelona

España

Novartis Pharma GmbH

Roonstrasse 25

90429 Nuremberg

Alemania

Lek Pharmaceuticals d.d.

Verovskova Ulica 57

1526 Ljubljana

Eslovenia

Novartis Pharma GmbH

Sophie-Germain-Strasse 10

90443 Nürnberg

Alemania

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

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

Instructions for use of Ilaris injectable solution

Read these instructions completely before injecting.

• It is essential that you do not attempt to inject it yourself until you have been instructed by your healthcare professional.
• See also section 3, «Self-injection of Ilaris or injection of Ilaris in a patient».

Essential preparations:

• Find a clean site to prepare and administer the injection to yourself.
• Wash your hands with water and soap, then dry them with a clean towel.
• After removing the vial from the refrigerator, check the expiration date of the vial. Do not use them after the expiration date that appears on the label and packaging. The expiration date is the last day of the month indicated.
• Leave the vial unopened for 10minutes to allow the contents to reach room temperature. Do not attempt to heat the vial. Let it warm up on its own.
• Always use new syringes and needles that are in sealed packages. Do not touch the needles or the vial stopper.

Assemble all the elements you need:

Included in the package

• one vial of Ilaris injectable solution (keep in the refrigerator).

Not included in the package

• a syringe of1,0ml
• a needle (such as an 18G or 21Gx2 inches or similar, depending on market availability) to extract the solution from the vial(“extraction needle”).
• a needle of 27Gx0.5 inches (or similar, depending on market availability) for the injection («injection needle»)
• alcohol wipes
• dry and clean cotton
• a adhesive bandage
• a suitable container for disposing of the needles, syringe, and vial used (sharps container)

Preparing the injection

Administering the injection

After the injection