KINERET

Package leaflet: Information for the user

Kineret 100 mg/0.67 mL solution for injection in pre-filled syringe

anakinra
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

1. What Kineret is and what it is used for
2. What you need to know before using Kineret
3. How to use Kineret
4. Possible side effects
5. How to store Kineret
6. Contents of the pack and other information

1. What Kineret is and what it is used for

Kineret contains the active substance anakinra, a type of cytokine (an immunosuppressive agent) used to treat:

• Rheumatoid arthritis (RA)
• COVID-19 in patients with pneumonia who require supplemental oxygen and are at risk of developing respiratory failure
• Periodic fever syndromes:
• Cryopyrin-associated periodic syndromes (CAPS), or neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurological, cutaneous, articular syndrome (CINCA), or Muckle-Wells syndrome (MWS), or familial cold autoinflammatory syndrome (FCAS)
• Familial Mediterranean fever (FMF)
• Still’s disease, including systemic juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD)

Cytokines are proteins produced by the body that coordinate communication between cells and help regulate cellular activity. In RA, CAPS, FMF, Still’s disease and COVID-19 pneumonia, the body produces excessive amounts of a cytokine called interleukin-1, which causes harmful effects leading to inflammation and disease symptoms. Normally, the body produces a protein that blocks the harmful effects of interleukin-1. The active ingredient in Kineret, anakinra, works in the same way as this naturally occurring interleukin-1 blocking protein. Anakinra is produced using recombinant DNA technology with the microorganism E. coli.

For RA, Kineret is used to treat the signs and symptoms of the disease in adults (age ≥ 18 years) in combination with another medicine called methotrexate. Kineret is intended for patients who have an inadequate response to methotrexate, meaning their rheumatoid arthritis is not adequately controlled.

For COVID-19, Kineret is used to treat hyperinflammation (an inflammation stronger than usual) associated with the disease in adults (age ≥ 18 years) who have pneumonia, require supplemental oxygen to help them breathe (low or high flow oxygen), and are at risk of developing respiratory failure.

For CAPS, Kineret is used to treat signs and symptoms of inflammation associated with the disease such as rash, joint pain, fever, headache, and fatigue in both adult and pediatric patients (age ≥ 8 months).

For FMF, Kineret is used to treat signs and symptoms of inflammation associated with the disease such as recurrent fever, fatigue, abdominal pain, muscle or joint pain, and rash. When appropriate, Kineret may be used in combination with colchicine.

For Still’s disease, Kineret is used to treat signs and symptoms of inflammation associated with the disease such as rash, joint pain, and fever.

2. What you need to know before using Kineret

Do not use Kineret

• if you are allergic to anakinra or to any of the other ingredients of this medicine (listed in section 6);
• if you are allergic to other products made using DNA technology with the microorganism E. coli;
• if you have neutropenia (reduced white blood cell count) as determined by a blood test.

Contact your doctor immediately

• if you develop a rash all over your body, difficulty breathing, shortness of breath, rapid pulse, or sweating after an injection of Kineret. These symptoms may indicate that you are allergic to Kineret;
• if you have previously developed widespread, atypical rash or skin peeling after taking Kineret.

Warnings and precautions
Talk to your doctor before using Kineret:

• if you have a history of recurrent infections or if you have asthma. Kineret may worsen these conditions;
• if you have a tumor. Your doctor will need to decide whether you can still receive Kineret;
• if you have a history of elevated liver enzymes;
• if you need to be vaccinated. You must not receive any live vaccine while being treated with Kineret.

Still’s disease

• Rarely, patients with Still’s disease, especially children, may develop lung disease, even during treatment with Kineret. The risk may be higher in patients with Down syndrome (trisomy 21). Symptoms of lung disease may include, for example, breathlessness during mild physical activity, morning cough, and difficulty breathing. If you experience signs of lung disease, contact your doctor as soon as possible.
• A serious skin reaction called drug reaction with eosinophilia and systemic symptoms (DRESS) has been rarely reported during treatment with Kineret, primarily in children with Still’s disease [systemic juvenile idiopathic arthritis (SJIA)]. Contact your doctor immediately if you notice a widespread, unusual rash, which may be accompanied by high fever and swollen lymph nodes.

CAPS:

• There have been reports of systemic amyloidosis (a condition characterized by the accumulation of abnormal proteins in organs and tissues) in patients with NOMID/CINCA who initially developed nodules under the skin at injection sites (amyloid deposits). These patients had been using anakinra at high doses for many years. Symptoms of systemic amyloidosis may include swelling (especially in legs and ankles), foamy urine, increased or decreased frequency of urination, muscle cramps, unexplained weight loss, diarrhea or constipation, and fatigue. Inform your doctor if you notice any of these symptoms.

Children and adolescents

• RA: The use of Kineret in children and adolescents with rheumatoid arthritis has not been fully studied and therefore cannot be recommended.
• COVID-19: The use of Kineret in children and adolescents with COVID-19 has not been studied and therefore cannot be recommended.
• CAPS, FMF, Still’s disease: Kineret is not recommended for children under 8 months of age due to lack of data in this age group.

Other medicines and Kineret
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
So-called tumor necrosis factor (TNF-α) inhibitors, such as etanercept, must not be taken together with Kineret, as this combination may increase the risk of infections.
As chronic inflammation decreases after taking Kineret, it may be necessary to adjust the doses of certain other medicines, e.g., warfarin or phenytoin.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor before taking this medicine.
Kineret has not been studied in pregnant women. The use of Kineret is not recommended during pregnancy and in women of childbearing potential who are not using contraception. It is important that you inform your doctor if you are pregnant, think you may be pregnant, or are planning a pregnancy. Your doctor will discuss with you the potential risks associated with taking Kineret during pregnancy.
It is not known whether anakinra is excreted in breast milk. If you are using Kineret, you must stop breastfeeding.

Kineret contains sodium and polysorbate 80
This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg dose, i.e., essentially ‘sodium-free’.
This medicine contains 0.70 mg of polysorbate 80 per pre-filled syringe, equivalent to 1.04 mg/mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Kineret

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist. Kineret must be administered as a subcutaneous (under the skin) injection once daily. You should try to administer the injection at the same time each day.
The recommended dose ranges from 20 to 90 mg or 100 mg. Your doctor will tell you the dose you need, or if you should take a dose higher than 100 mg.
COVID-19: the recommended dose is 100 mg injected subcutaneously (under the skin) once daily for 10 days.
How to self-administer Kineret injections
Your doctor may consider it more convenient for you to self-inject Kineret. Your doctor or nurse will show you how to administer the injection yourself. Do not attempt to self-inject unless you have been properly instructed.
Refer to the section at the end of this leaflet for instructions on how to self-administer the Kineret injection.

Kineret alone or how to administer the injection to your child.

If you use more Kineret than you should
If you accidentally use more Kineret than prescribed, the consequences are unlikely to be serious. However,
you should still contact your doctor, nurse, or pharmacist. If you feel unwell, seek immediate advice from your doctor or nurse.
If you forget to use Kineret
If you have forgotten to take a dose of Kineret, contact your doctor to determine when to take the next dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
The possible side effects are similar whether Kineret is taken for RA, CAPS, FMF, Still’s disease or COVID-19.
If you notice any of the following effects, inform your doctor immediately:

• Serious infections, such as pneumonia (an infection in the chest) or skin infections, may occur while taking Kineret. Symptoms may include persistent high fever, chills, cough, headache, and redness and tenderness of the skin. Persistent low-grade fever, weight loss, and persistent cough may also be signs of infection.
• Serious allergic reactions are uncommon. However, any of the following symptoms may indicate an allergic reaction to Kineret, so inform your doctor immediately. Do not inject Kineret again.
• Swelling of the face, tongue or throat
• Difficulty swallowing or breathing
• Sudden rapid heartbeat or sweating
• Skin itching or rash
• Drug reaction with eosinophilia and systemic symptoms ( DRESS ), a severe skin reaction, has been rarely reported during Kineret therapy, mainly in children with Still’s disease (systemic juvenile idiopathic arthritis). Signs of DRESS may include an unusual and widespread rash, which may be associated with high fever and swollen lymph nodes.

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

• Redness, swelling, bruising or itching at the injection site. These symptoms range from mild to moderate and are more common at the beginning of treatment.
• Headaches.
• Increased total cholesterol.

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

• Neutropenia (low number of white blood cells) found in a blood test. This may increase the risk of getting an infection. Signs of infection may include, among others, fever or sore throat.
• Serious infections, such as pneumonia (an infection in the chest) or skin infections.
• Thrombocytopenia (low levels of platelets in the blood).

Uncommon side effects (may affect up to 1 in 100 people):

• Serious allergic reactions including swelling of the face, tongue or throat, difficulty swallowing or breathing, sudden rapid heartbeat or sweating, and skin itching or rash.
• Elevated liver enzyme levels detected by a blood test.

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• Signs of liver problems such as yellowing of the skin and eyes, nausea, loss of appetite, dark urine and pale stools.
• If Kineret is injected repeatedly in the same area, there is a risk of developing a nodule (amyloid deposit) under the skin. To avoid this, alternate the injection site.
• Signs of an unusual and widespread skin rash, which may be associated with high fever and swollen lymph nodes.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Kineret

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and carton after Scad/EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C - 8 °C). Do not freeze.
Keep in the original packaging to protect from light.
Do not use Kineret if you think it has been frozen. Once the syringe has been removed from the refrigerator and has reached room temperature (up to 25 °C), it must be used within 72 hours or be discarded. Do not return it to the refrigerator if it has been stored at room temperature.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Kineret contains

• The active substance is anakinra. Each pre-filled graduated syringe contains 100 mg of anakinra.
• The other components are citric acid anhydrous, sodium chloride, edetate disodium dihydrate, polysorbate 80, sodium hydroxide and water for injections.

Description of the appearance of Kineret and contents of the pack
Kineret is a clear, colourless to opalescent injectable solution, supplied ready-to-use in a pre-filled syringe. It may contain some protein particles ranging from translucent to white. The presence of these particles does not affect the quality of the product.
Pack sizes of 1, 7 or 28 (multi-pack box containing 4 packs of 7 pre-filled syringes) pre-filled syringes.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Swedish Orphan Biovitrum AB (publ)
SE-112 76 Stockholm
Sweden
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu .

INSTRUCTIONS FOR PREPARING AND ADMINISTERING A KINERET INJECTION
This section contains information on how to self-administer a Kineret injection or administer it to your child. Do not attempt to give the injection to yourself or your child unless a doctor, nurse or pharmacist has shown you how to do so. For any questions about how to administer the injection, consult your doctor, nurse or pharmacist.
How should the pre-filled Kineret syringe be used?
The injection must be given at the same time each day. Kineret is injected just under the skin: this technique is called a subcutaneous injection.

Equipment
To administer a subcutaneous injection to yourself or your child, you will need:

• one pre-filled syringe of Kineret
• alcohol swabs or similar; and
• a sterile gauze or tissue.

What should you do before administering a subcutaneous injection of Kineret to yourself or your child?

1. Remove the Kineret syringe from the refrigerator.
2. Do not shake the pre-filled syringe.
3. Check the expiry date on the label of the pre-filled syringe (EXP). Do not use the medicine after the last day of the month indicated.
4. Check the appearance of Kineret. The medicine should be a clear, colourless to opalescent solution. The solution may contain protein particles ranging from translucent to opalescent. The presence of these particles does not affect the quality of the product. Do not use the solution if it shows changes in colour, appears cloudy, or if particles other than translucent to opalescent particles are present.
5. For a more comfortable injection, allow the pre-filled syringe to warm to room temperature for about 30 minutes or hold it gently in your hand for several minutes. Do not heat Kineret in any other way (for example, do not heat the medicine in a microwave or in warm water).
6. Do not remove the cap from the syringe until you are ready to administer the injection.
7. Wash your hands thoroughly.
8. Find a clean, well-lit, comfortable surface and arrange all necessary equipment within easy reach.
9. Make sure you know the dose of Kineret prescribed by your doctor: 20–90 mg, 100 mg, or a higher dose.
   • If your doctor has prescribed a dose of 100 mg, go to the section “How to prepare a 100 mg dose”.
   • If your doctor has prescribed a lower dose, go to the section “How to prepare a 20–90 mg dose”.

How to prepare a 100 mg dose
Before administering the Kineret injection, do the following:

1. Hold the syringe barrel and gently remove the needle cap without twisting. Pull straight off, as shown in Figure A. Do not touch the needle or press the plunger. Immediately discard the needle cap.
2. There may be a small air bubble in the pre-filled syringe. It is not necessary to remove it before administering the injection. Injecting the solution with the air bubble will not cause harm.
3. You may now use the pre-filled syringe as described in the sections “Where to give the injection?” and “How to administer the injection?”.

How to prepare a 20–90 mg dose
Before administering the Kineret injection, do the following:
Figure A

1. Hold the syringe barrel and gently remove the needle cap without twisting. Pull straight off, as shown in Figure A. Do not touch the needle or press the plunger. Immediately discard the needle cap.
2. Hold the syringe in one hand with the needle pointing upward, as shown in Figure B. Place your thumb on the top of the plunger and slowly press until a small drop of liquid appears at the tip of the needle.
3. Rotate the syringe so that the needle points downward.

Place a sterile gauze or tissue on a flat surface and hold the syringe above it with the needle pointing toward the gauze or tissue, as shown in Figure C. Make sure the needle does not touch the gauze or tissue.

4. Place your thumb on the top of the plunger and slowly press until the front edge of the plunger reaches the mark on the scale corresponding to the prescribed dose of Kineret (your doctor will have told you which dose to use). The expelled liquid will be absorbed by the gauze or tissue, as shown in Figure C.
5. If you cannot set the correct dose, discard the syringe and use a new one.
6. You may now use the pre-filled syringe as described in the sections “Where to give the injection?” and “How to administer the injection?”.

Where to give the injection?
The best sites for administering the injection to yourself or your child are (see Figure D):

• the abdomen (except the area around the navel)
• the upper thighs
• the outer upper buttocks; and
• the outer areas of the arms

Adult Child

Figure D
Change the injection site each time to avoid soreness in one area. If the injection is administered by someone else, the back of the arms may also be used.
How to administer the injection?

1. Clean the skin using an alcohol swab and pinch the skin between your thumb and index finger, without squeezing it tightly.
2. Insert the needle completely into the skin as shown to you by the nurse or doctor.
3. Inject the liquid slowly and steadily, keeping the skin fold as shown in Figure E.

Figure E

4. After injecting the liquid, remove the needle and release the skin.

Fi E

5. Any unused solution must be discarded. Use each syringe for only one injection. Do not reuse a syringe, as this may lead to infection.

Remember
If you have any problems, do not hesitate to contact your doctor or nurse for help and advice.
Disposal of used syringes and equipment

• Do not recap used needles.
• Keep syringes out of the reach and sight of children.
• Never dispose of used pre-filled syringes in household waste.
• If you have used a dose lower than 100 mg, you were instructed to expel the remaining liquid from the syringe onto a gauze or tissue. After the injection, discard the wet gauze or tissue together with the syringe and clean the surface with a new tissue.
• Used pre-filled syringes and any gauze or tissue containing Kineret solution must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.