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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

anakinra

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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the 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. It is a type of cytokine (an immunosuppressive agent) used to treat:

• Rheumatoid arthritis (RA)

• COVID‑19 in patients who have pneumonia, require supplemental oxygen, and are at risk of respiratory failure

• Periodic fever syndromes:

• Cryopyrin-associated periodic syndromes (CAPS)

  • Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurological, cutaneous and articular syndrome (CINCA)
  • Muckle-Wells syndrome (MWS)
  • 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 our body that coordinate communication between cells and help regulate cellular activity. In RA, CAPS, FMF, Still’s disease, and pneumonia due to COVID‑19, the body produces excessive amounts of a cytokine called interleukin‑1. This leads to harmful effects causing inflammation and the symptoms of the disease. Normally, the body produces a protein that blocks the harmful effects of interleukin‑1. The active substance in Kineret, anakinra, works in a manner similar to this natural protein that blocks interleukin‑1. Anakinra is produced by recombinant DNA technology using the microorganism E. coli.

In RA, Kineret is used to treat the signs and symptoms of the disease in adults (from 18 years of age) in combination with another medicine called methotrexate. Kineret is intended for patients who do not respond adequately to methotrexate alone in controlling rheumatoid arthritis.

In COVID‑19, Kineret is used to treat hyperinflammation (more severe than usual inflammation) associated with the disease in adults (from 18 years of age) who have pneumonia, require supplemental oxygen to assist breathing (low or high flow oxygen), and are at risk of respiratory failure.

In CAPS, Kineret is used to treat the signs and symptoms of inflammation associated with this disease, such as rash, joint pain, fever, headache, and fatigue, in both adults and children (from 8 months of age).

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

In Still’s disease, Kineret is used to treat the signs and symptoms of inflammation associated with this 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 recombinant DNA technology employing the microorganism E. coli
• if you have neutropenia (low white blood cell count) determined by a blood test.

Contact your doctor immediately

• if you develop a rash all over your body, have difficulty breathing, wheezing, rapid pulse, or sweating after injecting Kineret. These may be symptoms of an allergic reaction to Kineret.
• if you have ever had an atypical widespread rash or skin peeling after taking Kineret.

Warnings and precautions

Talk to your doctor before starting Kineret:

• if you have a history of recurrent infections or if you have asthma, as Kineret may worsen these conditions
• if you have cancer. Your doctor will need to decide whether you can receive Kineret
• if you have a history of increased liver enzyme levels
• if you need vaccination. You should not receive live vaccines 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 increased in patients with Down syndrome (trisomy 21). Symptoms of lung disease may include, for example, shortness of breath during mild exercise, morning cough, and difficulty breathing. If you develop signs of lung disease, contact your doctor as soon as possible.
• A serious skin reaction, DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms), has rarely been reported with Kineret treatment, particularly in children with Still’s disease (systemic juvenile idiopathic arthritis [SJIA]). Seek immediate medical attention if you notice an atypical widespread rash, which may appear along with high fever and swollen lymph nodes.

CAPS

• A few cases of systemic amyloidosis (a condition in which abnormal proteins accumulate in tissues and organs) have been reported in patients with NOMID/CINCA, initially presenting as lumps under the skin at injection sites (amyloid deposits). These patients had been using anakinra at high doses for several years. Symptoms of systemic amyloidosis may include swelling (especially in the 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 (RA) has not been thoroughly investigated 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: The use of Kineret is not recommended in children under 8 months of age, as data are not available for this age group.

Other medicines and Kineret

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines.

Medicines called tumour necrosis factor (TNF-α) inhibitors, such as etanercept, should not be used together with Kineret, as this could increase the risk of infections.

When you start using Kineret, chronic inflammation in your body will decrease. This may require dose adjustments of certain other medicines, such as warfarin or phenytoin.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine.

Kineret has not been studied in pregnant women. The use of Kineret is not recommended during pregnancy or 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 plan to become pregnant. Your doctor will discuss with you the potential risks of taking Kineret during pregnancy.

It is unknown whether anakinra is excreted in human milk. Discontinue breastfeeding if you are using Kineret.

Kineret contains sodium and polysorbate 80

This medicine contains less than 1 mmol of sodium (23 mg) per 100 mg dose; essentially "sodium-free".

This medicine contains 0.70 mg of polysorbate 80 in each pre-filled syringe, equivalent to 1.04 mg/ml. Polysorbates may cause allergic reactions. Inform your doctor if you have any known allergies.

3. How to use Kineret

Follow exactly the instructions for administering this medicine as given by your doctor. If in doubt, consult your doctor or pharmacist again. Kineret is injected under the skin (subcutaneous injection) daily. You should try to administer the injection at the same time each day.

The recommended dose is 20 to 90 mg or 100 mg. Your doctor will determine the dose you need, or whether you require a dose higher than 100 mg.

COVID‑19: the recommended dose is 100 mg injected under the skin (subcutaneously) daily for 10 days.

Self-administration of Kineret

Your doctor may decide it is more convenient for you to self-inject Kineret. Your doctor or nurse will show you how to do this. Do not attempt to self-inject unless you have been properly instructed.

For information on how to self-inject Kineret or how to inject it to your child, please read the section “Instructions for preparing and administering a Kineret injection” included at the end of this leaflet.

If you use more Kineret than you should

You should not experience any serious problems if you accidentally use more Kineret than you need. However, you should contact your doctor or pharmacist if this happens. If you feel unwell, you must contact your doctor immediately.

If you forget to use Kineret

If you forget to take a dose of Kineret, you should contact your doctor to discuss when you should take the next dose.

4. Possible side effects

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

The possible side effects are similar whether Kineret is used for RA, CAPS, FMF, Still's disease, or COVID‑19.

If any of the following side effects occur, inform your doctor immediately:

• Serious infections, such as pneumonia (chest infection) or skin infections, may occur during treatment with Kineret. Symptoms may include persistent high fever, chills, cough, headache, and redness and pain in the skin. Other possible signs of infection are low-grade fever, weight loss, and persistent cough.

• Severe allergic reactions are uncommon. However, any of the following symptoms may indicate a serious allergic reaction to Kineret, and you should seek immediate medical attention. Do not inject further doses of Kineret:

• Swelling of the face, tongue, or throat

• Difficulty swallowing or breathing

• Sudden sensation of rapid heartbeat or sweating

• Itching or skin rash

• Rarely, a drug reaction with eosinophilia and systemic symptoms (DRESS), a severe skin reaction, has been reported with Kineret treatment, particularly in children with Still's disease (systemic juvenile idiopathic arthritis [sJIA]). Signs of DRESS may include a widespread atypical rash, which may appear along with high fever and enlarged 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 are usually mild to moderate and occur more frequently at the beginning of treatment.
• Headache.
• Increased total blood cholesterol levels.

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

• Neutropenia (low number of white blood cells) detected by blood test. Neutropenia may increase your risk of developing an infection. Symptoms of infection may include fever or sore throat.
• Serious infections such as pneumonia (chest infection) or skin infections.
• Thrombocytopenia (low number of platelets in the blood).

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

• Severe allergic reactions including swelling of the face, tongue, or throat, difficulty swallowing or breathing, sudden sensation of rapid heartbeat or sweating, itching, or rash.
• Elevated liver enzymes detected by blood test.

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

• Signs of liver disorders, such as yellowing of the skin and eyes, nausea, loss of appetite, dark-colored urine, and very pale stools.
• If Kineret is repeatedly injected in the same location, there is a risk of developing a lump (amyloid deposit) under the skin. Rotate injection sites to avoid this.
• Signs of a widespread atypical rash, which may appear along with high fever and enlarged lymph nodes.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 the carton after “EXP”. The expiry date refers to the last day of the month indicated.

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

Keep in the original carton to protect from light.

Do not use Kineret if you think it has been frozen. Once a syringe has been removed from the refrigerator and has reached room temperature (up to 25 °C), it must be used within 72 hours or discarded. Do not return it to the refrigerator if it has been stored at room temperature.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicines and packaging. This helps protect the environment.

6. Package contents and additional information

Composition of Kineret

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

Appearance of the medicinal product and contents of the container

Kineret is a clear, colourless to slightly whitish solution supplied in a pre-filled syringe ready for use. The solution may contain protein particles appearing translucent to white; their presence does not affect the quality of the product.

Pack sizes of 1, 7 or 28 (multiple pack containing 4 packs of 7 pre-filled syringes) pre-filled syringes.

Only certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Swedish Orphan Biovitrum AB (publ)
SE‑112 76 Stockholm
Sweden

Date of the most recent revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

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INSTRUCTIONS FOR PREPARING AND ADMINISTERING A KINERET INJECTION

This section contains information on how to self-administer Kineret or administer it to your child. It is important that you do not attempt to administer the injection yourself or to your child unless you have been trained to do so by a doctor, nurse, or pharmacist. If you have any doubts about how to give the injection, please consult your doctor, nurse, or pharmacist.

How should you or the person administering the injection use the Kineret pre-filled syringe?

You will need to administer an injection to yourself or to your child every day at the same time. Kineret is injected under the skin. This is known as a subcutaneous injection.

Materials:

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

• one Kineret pre-filled syringe;
• an alcohol swab or similar; and
• sterile gauze or dressing.

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

1. Remove the Kineret pre-filled syringe from the refrigerator.

2. Do not shake the pre-filled syringe.

3. Check the expiry date printed on the label of the pre-filled syringe (EXP). Do not use it if the current date is beyond the last day of the month indicated.

4. Check the appearance of Kineret. It should be a clear, colourless to slightly whitish solution. The solution may contain protein particles appearing translucent to white; their presence does not affect the quality of the product. Do not use this medicine if it has a different colour, is cloudy, or if the particles present are not translucent to white.

5. For more comfortable administration, allow the pre-filled syringe to reach room temperature for approximately 30 minutes, or hold it gently in your closed hand for a few minutes. Do not heat Kineret in any other way (for example, do not use a microwave or warm water).

6. Do not remove the syringe cap until you are ready to administer the injection.

7. Wash your hands thoroughly.

8. Find a clean, comfortable, well-lit surface and place all necessary materials within easy reach.

9. Make sure you know the dose of Kineret prescribed by your doctor: 20 to 90 mg, 100 mg, or greater than 100 mg.

   • 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 dose less than 100 mg, go to the section "How to prepare a dose of 20 to 90 mg?"

How to prepare a 100 mg dose?

Before injecting Kineret, you must do the following:

How to prepare a dose of 20 to 90 mg?

Where should the injection be given?

The most suitable places for you to give the injection to yourself or to your child are (see Figure D):

• the abdomen (except the area around the navel)
• the upper part of the thighs
• the upper outer area of the buttocks
• the outer upper area of the arms

Change the injection site each time to avoid irritation or discomfort in any one area. If someone else is giving the injection, it may also be administered into the back of the arms.

How to give the injection

1. Disinfect the skin using an alcohol wipe and pinch the skin between your thumb and index finger, without squeezing tightly.

2. Insert the needle completely into the skin as shown and instructed by your nurse or doctor.

3. Inject the liquid slowly and steadily, keeping the skin pinched throughout, as shown in Figure E.

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

5. Any unused medicine should be discarded. Each syringe should only be used for one injection. Do not reuse syringes, as this may cause infection.

Remember

If you have any difficulty, ask your doctor or nurse for help and advice.

How to dispose of used syringes and additional materials

• Do not recap used needles.

• Keep used syringes out of the reach and sight of children.

• Never dispose of used pre-filled syringes in your household waste bin.

• If your dose is less than 100 mg, you must pour any remaining liquid from the syringe onto a piece of gauze or dressing. After the injection, dispose of the damp gauze or dressing together with the syringe, and clean any contaminated surface with a clean cloth.

• Pre-filled syringes, as well as gauze or dressings soaked with Kineret solution, must be disposed of in accordance with local regulations. Ask your pharmacist how to dispose of medicines you no longer need. This will help protect the environment.