Ruconest - Conestat alfa uses, dose and side effects

Ruconest contains conestat alfa as an active substance. Conestat alfa is a recombinant (not produced from blood) form of human C1 inhibitor (real-INH).

Ruconest is for use in adults, adolescents, and children (2 years of age and older) with a rare hereditary problem of blood disease, hereditary angioedema (HAE). HAE patients have a deficiency of C1 inhibitor protein in their blood. This can lead to recurrent seizures with swelling, abdominal pain, difficulty breathing, and other symptoms.

Ruconest is given to treat the C1 inhibitor deficiency and relieve the symptoms of acute hereditary angioedema (HAE).

What you need to know before using Ruconest

Do not use Ruconest

if you are or think you may be allergic to rabbits.
if you are allergic to conestat alfa or any of the other ingredients of this medicine (listed in section 6).

Warnings and cautions

Talk to your doctor before using Ruconest.

If you experience allergic reactions, e.g. hives, rash, itching, dizziness, wheezing, difficulty breathing or if the tongue swells up after receiving Ruconest, you should seek emergency care so that your allergic symptoms can be treated immediately.

Children and young people

Ruconest should not be given to children under 2 years of age. Ruconest has not been studied in children younger than 5 years. Your doctor will decide if it is appropriate to treat your child with Ruconest. Additional monitoring of your child for symptoms of allergic reactions during and after administration is required.

Other medicines and Ruconest

Tell your doctor or pharmacist if you have recently taken, or might take any other medicines.

If you are receiving tPA (tissue-type plasminogen activator ) as an acute treatment for thrombosis, you should not be treated with Ruconest at the same time.

Pregnancy and breastfeeding

Ruconest is not recommended during pregnancy and lactation.

If you are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

Do not drive or use any tools or machines if you feel dizzy or have a headache after taking Ruconest.

Ruconest contains sodium (19.5 mg per vial)

This should be considered by patients on a low-sodium diet.

How to use Ruconest

Ruconest treatment should be started by a doctor who specializes in the diagnosis and treatment of hereditary angioedema.

Ruconest must be given by a doctor or nurse until you or your carer have received adequate training in how to use Ruconest and can inject the medicine.

Always use this medicine exactly as described in this leaflet or as directed by your doctor or nurse. If you are not sure, talk to your doctor or nurse.

Ruconest is given to a friend for about 5 minutes. Dose one is calculated according to your body weight.

One dose is usually enough. An additional dose may be administered if your symptoms do not improve after 120 minutes (for adults and adolescents) or after 60 minutes (for children). A maximum of two doses, calculated according to step 7, should be given within 24 hours.

You or your healthcare provider must not inject Ruconest until your doctor or nurse has given you adequate instructions and appropriate training on how to use the medicine.

Instructions for use

Ruconest must not be mixed or given with other medicines or solutions. Below is a description of how the Ruconest solution is to be prepared and given.

Before you begin

Make sure the kit is complete and contains all the components listed in section 6 of this leaflet.
In addition to the kit, the following is needed:
- a constriction bandage
- tape to attach the needle
Inspect vials and other components.
- all vials must be sealed with plastic lids and aluminum lids and must not have visible damage, e.g. cracks in the glass.
- check the expiration date. Never use kit components after the expiration date indicated on the large outer carton. Within the same kit box, different components can have different expiration dates. The expiry date on the outer carton shows the date of the component with the shortest shelf life.
Allow the number of vials of powder and liquid needed for step 1 to reach room temperature.

Prepare solution

Step 1: Cleaning and other requirements

Wash your hands thoroughly.
Place the vials of powder and liquid on a flat and clean surface.
- body weight 42 kg or less: 1 vial of powder and 1 vial of liquid
- body weight over 42 kg: 2 vials of powder and 2 vials of liquid
Place the vial adapters on the work surface. Do not remove the adapter package.
- 2 adapters if needed 1 vial of powder and 1 vial of liquid
- 4 adapters if needed 2 vials of powder and 2 vials of liquid
Place the syringe (s) on the work surface. Do not remove the syringe pack.
- 1 syringe if needed 1 vial of powder and 1 vial of liquid
- 2 syringes if needed 2 vials of powder and 2 vials of liquid.

Step 2: Disinfect the stoppers on the vials

Remove the plastic caps from the vials of powder and liquid.
Use an alcohol swab to disinfect the stoppers on the vials and wait at least 30 seconds until the stoppers have dried.
After disinfection, do not touch the plugs with your fingers or anything else.

Step 3: Mount the adapters on the vials

Take a packaged adapter in one hand and remove the lid. The adapter must remain in the plastic packaging.
Press the adapter onto a powder vial while penetrating the stopper until the adapter snaps onto the neck of the vial.
Leave the package on the adapter until you connect the syringe in steps 4 and 5.
Repeat the above steps for mounting an adapter on the vial of liquid. All adapters that come with the kit are identical.
If you need to use another powder vial and one with liquid, repeat the above steps.

Step 4: Draw up the liquid

Take a sterile syringe out of its package.
Remove the package from the adapter on the vial of liquid.
Hold the adapter with one hand. On the other hand, connect the syringe and secure it by turning it clockwise until it receives.
Turn the entire device – the vial of liquid, the adapter, and the syringe – upside down. Hold the device vertically while slowly drawing up 14 ml of liquid. If air bubbles are visible, minimize them as far as possible by tapping the syringe gently and applying a light pressure by pushing the plunger into the syringe. Continue to fill the syringe with 14 ml of liquid.
Release the syringe from the adapter by turning it counterclockwise.
Leave the rest of the liquid in the vial and discard the vial. Place the syringe on the work surface but do not allow the tip of the syringe to touch the surface or any other object.

Step 5: Add liquid to the powder and dissolve

Remove the package from the adapter on the powder vial.
Take the syringe with the liquid that you prepared in step 4.
Hold the adapter with one hand and connect the syringe. Secure the syringe by turning it clockwise until it receives.
To minimize foaming, inject the liquid slowly, in a single motion, into the powder vial.
Leave the syringe on the adapter and gently swirl the vial for about half a minute. Do not shake. After spinning, leave the vial on the work surface for a few minutes until the solution is ready. If there is still undissolved powder left, repeat the procedure.
Repeat steps 4 and 5 if you need to prepare another solution.

Step 6: Check ready-made solutions

Check that the powder in the vial (s) is completely dissolved and that the plunger is completely depressed in the syringe.
When the powder is dissolved, the solution should be clear and colorless.
Do not use the reconstituted solution if it is cloudy, contains particles, or has changed color. Inform healthcare professionals if this happens. Small amounts of foam are acceptable.

Step 7: Draw up the prepared solution

Calculate how many milliliters of the reconstituted solution is to be injected.

Body weight	Milliliters of reconstituted solution to be injected
under 84 kg	Body weight in kg divided by three
84 kg or more	28 ml

Pull up the volume of the reconstituted solution while holding the syringe vertically. If you have prepared:
- a vial of solution, draw up the calculated volume
- two vials and your body weight is below 84 kg, pull up similarly:
  1. 14 ml from the first vial
  2. from the second vial, draw the difference between your estimated volume and the 14 milliliters from the second vial
- two vials and your body weight is 84 kg or more, draw 14 ml from each vial into each syringe. If air bubbles are visible, minimize them as far as possible by tapping the syringe gently and creating a light pressure by pushing the plunger into the syringe. Continue to fill the syringe with the required volume.
Never exceed the volume of 14 ml per syringe.
Release the syringe (s) by turning it (them) counterclockwise and discarding the vial (s) together with the adapter.
Place the syringe (s) on the work surface, but do not allow the tip of the syringe to touch the surface or any other object.

Step 8: Check ready-made syringes

Check again that the volume of the syringe (s) you prepared in step 7 is correct.

Administration in a friend

The reconstituted solution must be injected directly into a vein and not into an artery or surrounding tissue.

Inject the Ruconest solution immediately after reconstitution, preferably while sitting.

Step 9: Required components

Check that all required components are on the work surface:
- 1 or 2 syringes with reconstituted solution
- 1 infusion set with 25 G-needle
- 1 alcohol compress
- 1 sterile nonwoven compress
- 1 patch
- 1 tightening bandage
- 1 piece of tape to attach the needle

Step 10: Prepare the infusion set

Remove the screw cap from the end of the infusion set. It’s the end without a needle.
Hold this end with one hand, connect the end of the syringe tip and secure by turning clockwise until it receives.
Hold the syringe with the tip facing up. Gently press the syringe plunger to fill the infusion set thoroughly with the reconstituted solution.
Check that there is no air in the syringe, infusion line, or needle.

Step 11: Prepare the injection site

Place the lacing bandage above the injection site – preferably in the middle of the upper arm. Tighten to compress the vein. Reinforce this by tying your hand.
Feel with your other hand for a suitable vein.
Carefully disinfect the injection site with an alcohol swab and allow the skin to dry.

Step 12: Administer the reconstituted solution

Remove the needle cover.
Carefully insert the needle on the infusion set, at as small an angle as possible, into the vein.
Secure the needle with a piece of tape, about 7 cm long, over the wings of the needle.
Gently pull the plunger back slightly until you see blood drawn in the tubing to make sure the needle is in the vein.
Release the lacing bandage.
If there is no blood in the tubing, pull out the needle, repeat all steps from the beginning of step 11, and move the needle.
If there is blood, gently inject the solution into the vein, as shown in the picture. Inject for about 5 minutes.
If you have prepared two syringes:
- fold the hose close to the coupling on the infusion set to prevent backflow.
- unscrew the empty syringe from the infusion set and replace it immediately with the other syringe.
fold back the tubing and gently inject this solution in the same way as the first syringe.

Step 13: After administration

Carefully remove the tape that secures the needle and pull the needle out of the vein.
Once you have pulled out the needle, press the sterile compress against the injection site for a few minutes to reduce bleeding.

Then put patches on the injection site.
Fold the yellow protective cap over the needle.
Safely dispose of the used infusion set with needle, unused solution, syringe and empty vial in a suitable container for medical waste as these materials may harm others if not disposed of properly. Do not reuse equipment.

Step 14: Document the administration

date and time of administration
the batch number on the label on the powder vial.

If you use more Ruconest than you should

Contact a doctor or the nearest hospital if this happens.

If you have any further questions on the use of this product, ask your doctor.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If your symptoms worsen and/or if you get a rash, tingling in the skin or difficulty breathing or if your face or tongue swells up, you should seek medical attention immediately. These symptoms may indicate that you have become allergic to Ruconest.

Ruconest can cause some side effects:

Common: may affect up to 1 in 10 users

Nausea

Uncommon: may affect up to 1 in 100 people

Abdominal pain, diarrhea
Irritating or stinging sensation or numbness in the mouth
Headache, dizziness
Decreased sensation in the skin or the arms or legs
Throat irritation
Hives
Swelling in the ears or the area around the ears

How to store Ruconest

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 the vial label after EXP. The expiration date is the last day of the specified month.

Do not store above 25 ° C.

Keep the vial of powder in its carton. Sensitive to light.

Before Ruconest can be given, the powder must be dissolved in the liquid provided in the package (see section 3).

After reconstitution of the drug, it should be used immediately.

Do not use this medicine if you notice after dissolving the powder that the solution is discolored or contains particles. Small amounts of foam are acceptable.

Contents of the packaging and other information

Content declaration

Powder vial :

The active substance is conestat alfa. One powder vial contains 2100 units of conestat alfa, equivalent to 2100 units per 14 ml after reconstitution or a concentration of 150 units/ml.
The other ingredients in the powder are sucrose, sodium citrate (E331), and citric acid.

Vial with liquid:

The ingredient in the liquid is water for injections.

What the medicine looks like and the contents of the pack

Ruconest is supplied in a glass vial containing a white to off-white powder for solution for injection together with a glass vial containing a clear, colorless liquid to dissolve the powder. Once the powder has been dissolved in water for injections, the solution is clear and colorless.

Ruconest is delivered as an administration kit in a box containing:

1 vial of 2,100 U powder
1 vial with 20 ml liquid
2 vial adapters
1 syringe
1 infusion set with 35 cm tube and 25 G needle
2 alcohol compresses
1 sterile nonwoven compress
1 patch

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder:

Pharming Group NV

Drawing 24

2333 CR Leiden

Netherlands

Manufacturer:

Pharming Technologies BV