Rilonacept Regeneron (previously Arcalyst) - patient leaflet, side effects, dosage

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

What is in this leaflet:

1.

What Rilonacept Regeneron is and what it is used for

2. What you need to know before you use Rilonacept Regeneron

Do not use Rilonacept Regeneron:

• if you are allergic to rilonacept or any of the other ingredients of this medicine (listed in section 6).
• if you have an active, severe infection.

Warnings and precautions

You should tell your doctor if you have:

• an infection;
• tuberculosis or you have been in close contact with someone who has had tuberculosis;
• a history of infections that keep coming back;
• been scheduled to receive any vaccines.

Children and adolescents

Rilonacept Regeneron is not recommended for children younger than 12 years of age.

Other medicines and Rilonacept Regeneron

Tell your doctor or pharmacist if you are using, have recently used or might use any oth

In particular, you should tell your doctor if you are using any of the below medicines:

• Other medicines that block interleukin-1, such as anakinra or canakinumab.
• Medicines called Tumour Necrosis Factor (TNF) inhibitors (such as etanercept, adalimumab, or infliximab) predominantly used in rheumatoid and autoimmune disease.
• Any other medicines for chronic disorders, as Rilonacept Regeneron can affect how the liver processes some medicines, such as warfarin (a blood thinner). Your doctor may need to perform some tests and adjust the dose of such medicines.

Pregnancy and breast-feeding

Rilonacept Regeneron has not been tested in pregnant women and should not be used during pregnancy unless clearly necessary. You should not become pregnant and must use birth control while using Rilonacept Regeneron and for at least six weeks after your last dose. If you are pregnant, think you may be

doctor for advice before taking this medicine.

The safety of Rilonacept Regeneron in breast-feeding women is unknown. If you are breast-feeding you should ask your doctor for advice before using Rilonacept Regeneron.

Driving and using machin

Some symptoms associated with CAPS or with Rilonacept Regeneron treatment, such as a spinning sensation (known as vertigo), may affect your ability to drive or use machines. If you feel a spinning sensation, do not drive or operate any tools or machines until you are feeling normal again.

urse or pharmacist for advice before taking any medicine.

3. How to use Rilonacept Regeneron

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Rilonacept Regeneron is intended for subcutaneous use. This means that it is injected through a short needle into the fatty tissue just under the skin.

How much Rilonacept Regeneron to use

Adults

• The starting dose is 2 injections of 2 millilitres (ml) solution each, given on the same day at 2 different areas of the body.
• After that, the recommended dose is 1 injection of 2 ml injected once weekly.

Adolescents (aged 12 to 17 years old)

The dose will depend on the body weight of the patient and will be different for each patient. Your doctor will tell you how much medicine to inject.

• The starting dose is 4.4 milligrams per kilogram of body weight, up to 320 milligrams (mg), given as

one or two injections.

• After that, the recommended dose is 2.2 milligrams per kilogram, up to 160 mg, once same day of the week.

In both cases your doctor will calculate the corresponding volume to inject. The d Regeneron may need to be adjusted as the child grows. Talk with your doctor before adjustments.

How to inject Rilonacept Regeneron

Rilonacept Regeneron is injected under the skin (subcutaneously). The first injection of Rilonacept Regeneron should be given under the supervision of a trained healthcare professional. You or your

caregiver will receive adequate training on how to mix the pow the dose, and administer the injection.

Please read the section “INSTRUCTIONS FOR USE OF RILONACEPT REGENERON POWDER FOR SOLUTION FOR INJECTION” at the end of this leaflet. If you have questions, contact your doctor, nurse, or pharmacist.

If you use more Rilonacept Regeneron than you should

If you accidentally inject more Rilonacept Regeneron than the recommended dose, you should contact your doctor right away.

If you forget to use Rilonacept Regeneron

If you miss a dose of Rilonacept Regeneron and remember within a few days, inject it as soon as you remember. The next dose should be injected at the next regularly scheduled time. Do not inject a double dose to make up for the forgotten dose. Do not inject Rilonacept Regeneron more frequently than once weekly.

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You must tell your doctor right away if any of the following serious side effects occur while you are using Rilonacept Regeneron:

• Serious infections. Tell your doctor right away if you develop symptoms of an infection while being treated with Rilonacept Regeneron, such as:

– fever lasting longer than 3 days, or any other symptoms possibly related to an infection, such as prolonged cough, prolonged headache or localised redness, warmth or swelling of your skin.

You must stop treatment with Rilonacept Regeneron if you develop a severe infection.

• Allergic reactions. If you develop signs of an allergic (hypersensitivity) reaction during treatment with Rilonacept Regeneron (such as chest tightness, wheezing, trouble breathing, severe dizziness or lightheadedness, swelling of lips, or rash during or after the injection) then stop taking Rilonacept Regeneron and tell your doctor right away.

Very common side effects (affects 1 or more users in 10)

• Reactions at injection site (such as redness, swelling, itching, and bruising at the injection site)
• Upper respiratory infection
• Sinus infection
• Headache

Common side effects (affects 1 to up to 10 users in 100)

• Viral infection
• Bronchitis
• Skin, eye, or ear infection
• Tiredness (fatigue)
• Increased blood pressure
• Pneumonia
• Stomach/Intestinal infection
• Dizziness
• Flushing
• Allergic reaction
• Anxiety
• Being unable to sleep (insomnia)

Uncommon side effects (affects 1 to up to 10 users in 1,000)

• Meningitis
• Inflammation of the eye (iritis)

Changes in your blood cholesterol levels or in your blood counts may also occur. These will be monitored by your doctor.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. How to st

nacept Regeneron

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator. Do not freeze.

Keep the vials in the outer carton in order to protect from light.

After preparing the Rilonacept Regeneron solution, it is best if used right away because it does not contain a preservative. If necessary, the product may be kept at room temperature, but should be used within 3 hours of mixing.

The solution is viscous, clear and colourless to pale yellow. Prior to injection, the solution should be carefully inspected for any discolouration or particulate matter. If there is discolouration or particulate matter in the solution, the product must not be used.

Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information- The active substance is rilonacept. Each vial of powder contains reconstitution, each ml of solution contains 80 mg rilonacept.220 mg rilonacept. Afteride, histidine, histidine e solvent is water for

• – The other ingredients in the powder are glycine, arginine hydroc hydrochloride monohydrate, polyethylene glycol 3350 and sucrose. injections.

What Rilonacept Regeneron looks like and contents of the pack

• – Solvent is provided in a 5 ml transparent plastic vial containing 5 ml water for injections. The solvent is a colourless liquid.

Each pack contains:

4 vials of powder for solution for injection

4 vials of solvent

8 disposable 3-ml syringes

8 disposable 27-gauge, /-inch needles

Marketing Authorisation Holder

Regeneron UK Limited

40 Bank Street

E14 5DS London

United Kingdom

Manufacturer

Brecon Pharmaceuticals Ltd

Wye Valley Business Park

Hay-on-Wye

HR3 5PG Hereford

United Kingdom

This leaflet was last revised in

This medicine has been given ‘conditional approval’. This means that there is more evidence to come about this medicine.

The European Medicines Agency will review new information on this medicine at least every year and this leaflet will be updated as necessary.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website

INSTRUCTIONS FOR USE OF RILONACEPT REGENERON POWDER FOR SOLUTION FOR INJECTION

See also section

Read these instructions all the way through before beginning.

Supplies needed:

The following items are included in each Rilonacept Regeneron dose pack:

8 sterile, 3-ml disposable syringes

8 sterile, disposable needles (27-gauge, /-inch)

4 vials of Rilonacept Regeneron powder

4 vials of sterile water (solvent)

You will also need to obtain these items from your pharmacist, which are n Regeneron dose pack:

Alcohol wipes

Gauze pads

A puncture-resistant container for disposal of

Ask your pharmacist for these supplies.

General guidelines when giving a Rilonacept Regeneron injection:

d year) on the Rilonacept Regeneron carton and vial. It is stated. Do not use Rilonacept Regeneron after the expiry date. The month.

er stopper on the Rilonacept Regeneron vial with your hands. If

, clean it with a fresh alcohol wipe.

If you touch a needle or the needle touches any surface, throw away the entire syringe into your puncture-resistant container and start over with a new syringe.

Do not reuse needles or syringes.

To protect yourself and others from possible needle sticks, it is very important to throw away every syringe, with the needle attached, in the puncture-resistant container right after use. Do not try to

recap

STEP 1: Setting up for an injection

• 1. Wash your hands thoroughly.

• 2. Put the following items on a clean flat surface (see Figure 1):

• 2 sterile, 3-ml disposable syringes
• one used for adding the sterile water (solvent) to the Rilonacept Regeneron powder
• one used for injection
• 2 sterile, disposable needles (27-gauge, /-inch)
• one used for adding the sterile water (solvent) to the Rilonacept Regeneron powder
• one used for injection
• 1 vial of Rilonacept Regeneron powder
• 1 vial of sterile water (solvent)
• 3 alcohol wipes
• 1 gauze pad
• 1 puncture-resistant container for disposal of used needles, syringes and vials

container

Figure 1

........

STEP 2: Preparing the vial of Rilonacept Regeneron powder

• 1. Remove the plastic cap from the Rilonacept Regeneron vial.

_O

• 2. Clean the top of the Rilonacept Regeneron vial with a fresh, never-used alcohol wipe, wiping in one direction around the top.

• 3. Set the vial aside.

STEP 3: Filling a syringe with sterile water for injection (solvent)

• 1. Snap off the plastic tab on the top of the vial containing sterile water for injection (solvent).

• 2. Open the wrapper that contains a 27-gauge needle by pulling apart the tabs. Place the capped needle on a clean surface. Open the wrapper that contains a syringe by pulling apart the tabs.

• 3. Attach the exposed top of the sterile water vial to the top of a syringe by twisting the syringe onto the vial of sterile water (solvent) (see Figure 2).

  4.

  
  

  5.

  
  

  Figure 2

  
  

  Hold the vial with the sterile water (solvent) in one hand and the syringe in the other hand.

  Carefully turn the vial upside down. While holding the syringe at eye level, slowly pull the syringe

  
  

  plunger back to the 2.5-ml line so that the sterile water (solvent) moves fro syringe (see Figure 3).

  
  

  Figure 3

  
  

  ial into the

  
  

  Remove the vial from 27-gauge needle onto

  
  

  inge. Hold the barrel of the syringe with one hand and twist the

  of the syringe with the other hand until it fits snugly (see Figure 4).

  
  

  Figure 4

  
  

6. Turn the syringe so that the needle is facing straight up. Pull the needle cap straight off. Do not twist the needle or the cap as you pull it off. Gently tap the syringe until air bubbles rise to the top of the syringe (see Figure 5).

Point the syringe and needle straight upward. The sterile water should be at the 2.3-ml line (see Figure 6). If there is more sterile water in syringe, then push the syringe plunger to force out sterile water until the water reaches the 2.3-ml line.

STEP 4: Dissolving Rilonacept Regeneron powder with the sterile water for injection (solvent)

• 1. With one hand, hold the Rilonacept Regeneron powder vial on a firm surface.

• 2. With the other hand, take the syringe with the sterile water (solvent) and slowly insert the needle straight down through the centre of the rubber stopper of the Rilonacept Regeneron powder vial. Push the syringe plunger down all the way so that the sterile water (solvent) in the syringe flows into the vial (see Figure 7).

Figure 7

• 3. Remove the syringe and needle from the stopper and throw away the syringe attached to the needle and sterile water (solvent) vial in the puncture-resistant container. Do not try to put the needle cover back on the needle.

• 4. Hold the vial containing the mixture of powder and sterile water (solvent) sideways (not upright) with your thumb and a finger at the top and bottom of the vial, and quickly shake the vial back and forth (side-to-side) for about 1 minute.

• 5. Put the vial back on the table and let the vial sit for about 1 minute.

• 6. Check if the vial contains any particles or clumps of powder that have not dissolved.

• 7. If the powder has not completely dissolved, shake the vial quickly back and forth for 30 seconds more. Let the vial sit for about 1 minute.

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• 8. Repeat step 7 until the powder is completely dissolved and the solution is clear.

• 9. The dissolved Rilonacept Regeneron solution should be a thick, clear liquid, colourless to pale yellow. Do not use the solution if it is discoloured or cloudy, or if it contains small particles (see Figure 8).

NOTE: Contact your pharmacy to report any dissolved Rilonacept Regeneron that is discoloured or contains particles.

Discolored/Cloudy

Figure 8

• 10. It is best to move to the next step and inject the medicine immediately after dissolving the Rilonacept Regeneron powder in the sterile water (solvent). If necessary, the product may be kept at room temperature (20 to 25°C) for no more than 3 hours. Keep Rilonacept Regeneron away from light.

STEP 5: Preparing the injection

Hold the vial with the solution on a firm surface and wipe the top of the vial with a ne wipe.

Open a wrapper containing a new, sterile, disposable needle. Open a wrapper containing a new, disposable syringe. Attach the needle securely to the syringe without removing the needle cover.

Hold the syringe upright at eye level. With the needle cover on, pull back the plunger on the syringe to the mark that is equal to the volume of the solution that your doctor has prescribed for you to inject, filling the syringe with air (see Figure 9).

Hold the vial in one hand and the syringe in the other hand and carefully turn the vial upside down so that the needle is pointing straight up. Hold the vial at eye level.

Keep the tip of the needle in the liquid and slowly pull back on the plunger to the mark on the syringe that matches the amount of medicine prescribed by your doctor (see Figure 11).

• 7. Tap the syringe until the air bubbles rise to the top of the syringe. Then slowly and gently, push in the plunger so that all of the air is pushed through the needle.

• 8. Check to make sure that you have the amount of medicine prescribed by your doctor in the syringe.

• 9. Throw away the vial in the puncture-resistant container even if there is some medicine left in the vial. Do not use any vial of Rilonacept Regeneron more than one time.

• 10. Hold the syringe and needle in your hand ready for injecting. Do not touch the needle with your hands or allow it to come into contact with any surfaces. Proceed with the injection as described in Step 6 below.

STEP 6: Giving the injection

• 1. Rilonacept Regeneron is injected into the tissue directly below the layers of skin. It is not meant to go into any muscle, vein, or artery.

Where to inject

Inject in a different place each time in order to keep your skin healthy.

Changing injection sites helps to prevent irritation and allows the medicine to be better absorbed. Ask your doctor any questions that you have about rotating injection sites.

• Do not inject into skin that is tender, red, or hard. If an area is tender or feels hardened, choose another site for injection until the tenderness or “hardening” goes away.
• Tell your doctor about any skin reactions including r skin.

s, swelling, or hardening of the

• Areas where you may inject Rilonacept Regeneron include the left and right sides of the abdomen, and left and right thighs. If someone else is giving you the injection, the upper arms

may also be used for injection (see Figure 12):

(Do not inject within a 5-cm area around the navel.)

• 2. Choose the area for the injection. Clean the area in a circular motion with a new alcohol wipe. Begin at the centre of the site and move outward. Let the alcohol air dry completely. Do not touch this area again before injecting.

• 3. Hold the syringe in one hand like you would hold a pencil.

• 4. With the other hand gently pinch a fold of skin around the site that you cleaned for injection.

• 5. Use a quick “dart like” motion to insert the needle straight into the skin (90° angle) (see Figure

13a). Do not push down on the plunger while inserting the needle into the skin. For small children or persons with little fat under the skin, you may need to hold the syringe and needle at a 45° angle (see Figure 13b).

Figure 13a (Adults)

Figure 13b (Small Children, Thin Patients)

• 6. After the needle is completely in the skin, let go of the skin that you are pinching.

• 7. With your free hand hold the syringe near its base. Gently pull back the plunger. If blood comes

into the syringe, the needle has entered a blood vessel. Remove the needle, discard the syringe and needle. Start over with ‘STEP 1: Setting up for an injection’ using new supplies.

• 8. If no blood appears, inject all the medicine in the syringe at a slow, steady rate, pushing the plunger all the way down. It may take up to 30 seconds to inject the entire dose.

• 9. Pull the needle out of the skin, and hold a piece of sterile gauze over the injection site for several seconds.

• 10. Do not replace the needle cover. Throw away the vials, used syringes and needles in the punctureresistant container. Do not recycle the container. Do not throw away vials, needles, or syringes in the household rubbish.

  11.

  12.

  
  

  Used alcohol wipes can be thrown away in the household rubbish.

  Keep the puncture-resistant container out of reach of children. When the container is about two-thirds full, dispose of it as instructed by your doctor or pharmacist.

  
  

Indication

Rilonacept Regeneron is indicated for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) with severe symptoms, including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS), in adults and children aged 12 years and older.

Posology

Adults

Treatment in adults should be initiated with a loading dose of 320 mg. Dosing should be continued with a once-weekly injection of 160 mg. Rilonacept Regeneron should not be given more often than once weekly.

Paediatric population (12 to 17 years old)

Treatment should be initiated with a loading dose of 4.4 mg/kg, up to a maximum of 320 mg. Dosing should be continued with a once-weekly injection of 2.2 mg/kg, up to a maximum of 160 mg (see Table 1). Dosing in children must be adjusted as the child grows. The patient or care giver should be advised to speak to the treating physician before adjusting the dose. The experience in children is limited. In the clinical program for CAPS, 8 adolescents aged 12–17 were treated for up to 18 months.

Paediatric population (up to 12 years old)

No data are available on the use of Rilonacept Regeneron in children with CAPS under 12 years of age, therefore it is not recommended in this paediatric age group.

Elderly (65 years old or older)

Available data indicate that dose modification is not required based on advanced age. However, clinical experience in patients above 65 years is limited, therefore caution is recommended.

Renal impairment

No dose adjustment is required in patients with mild, moderate or severe renal impairment, or end stage renal disease. However, clinical experience in such patients is limited.

Hepatic impairment

Rilonacept Regeneron has not been studied in patients with hepatic impairment.

Method of administration

Rilonacept Regeneron is for subcutaneous use only. It is not intended for intravenous or intramuscular use.

The adult loading dose should be administered as two 2 ml subcutaneous injections (320 mg of rilonacept in total) given on the same day at different sites. The subsequent doses are administered as a 2 ml (160 mg of rilonacept) subcutaneous injection once a week.

For paediatric patients, the dose is delivered as one or two (for loading dose) subcutaneous injections with a maximum single-injection volume of 2 ml.

For convenience, the corresponding dose volume for weekly injection in paediatric patients is presented in Table 1 below.

Special precautions for storage

Store in a refrigerator. Do not freeze.

Keep the vials in the outer carton in order to p

y be kept at room temperature, but should be used within contain a preservative.

Reconstitution and administration instructions

Instructions for reconstituti

Using aseptic technique, Rilonacept Regeneron powder should be reconstituted with 2.3 ml solvent (water for injections) prior to administration.

The 2.3 ml of solvent should be withdrawn from the solvent vial attached directly to a 3-ml syringe and

to the powder vial for reconstitution with 27-gauge, /-inch needle (to obtain a final reconstitution volume of 2.75 ml). The needle and syringe used for reconstitution with solvent should then be discarded and should not be used for subcutaneous injections. After the addition of solvent, the vial contents should be reconstituted by shaking the vial for approximately one minute and then allowing it to sit for one minute. The resulting 80 mg/ml solution is sufficient to allow a withdrawable volume of up to 2 ml for subcutaneous administration.

The reconstituted solution is viscous, clear and colourless to pale yellow. Prior to injection, the reconstituted solution should be carefully inspected for any discolouration or particulate matter. If there is discolouration or particulate matter in the solution, the product must not be used.

Instructions for administration

Using aseptic technique, the recommended dose volume, up to 2 ml (160 mg) of the solution should be withdrawn with a new 27-gauge, /-inch injection needle attached to a new 3-ml syringe for subcutaneous injection.

Sites for subcutaneous injection, such as the abdomen, thigh, or upper arm, should be rotated. Injections should never be made at sites that are bruised, red, tender, or hard.

The initial administration of Rilonacept Regeneron by a patient or caregiver should be under the guidance of a trained healthcare professional. For subsequent self-administration by patients, appropriate instruction in proper injection technique should be provided and ability to apply that technique ascertained.

Disposal

Each vial should be used for a single dose only. The vial should be discarded after withdrawal of the solution.

Patients or their caregivers should be instructed on the appropriate procedure for disposal of the vials, needles, and syringes.

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