Prospect: information for the patient

Ruconest 2100 units of powder and solvent for injectable solution

conestat alfa

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.

-This medication has been prescribed to you alone, and you must 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, even if they do not appear in this prospect. See section 4

1. What Ruconest is and for what it is used

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

3. How to use Ruconest

4. Possible adverse effects

5. Storage of Ruconest

6. Contents of the package and additional information

Ruconest contains conestat alfa as the active ingredient. Conestat alfa is a recombinant (non- plasma-derived) form of human C1 inhibitor (rhC1-INH).

Ruconest should be used by adults, adolescents, and children (from 2 years old) with a rare inherited blood disorder known as hereditary angioedema (HAE). These patients have a deficiency of the C1 inhibitor protein in their blood, which can cause repeated episodes of swelling, abdominal pain, difficulty breathing, and other symptoms.

The administration of Ruconest resolves the C1 inhibitor deficiency and allows for a reduction in symptoms of acute HAE attacks.

Do not use Ruconest:

• If you are or consider yourself allergic to rabbits
• If you are allergic to conestat alfa or any of the other components of this medication (listed in section 6).

Warnings and precautions

Consult your doctor before starting to use Ruconest.

If you experience allergic reactions, such as hives, rash, itching, dizziness, wheezing, difficulty breathing, or swelling of the tongue after administration of Ruconest, seek emergency medical assistance for urgent treatment of the allergic reaction symptoms.

Children and adolescents

Do not administer this medication to children under 2 years old. Ruconest has not been studied in children under 5 years old. Your doctor will determine if treatment with Ruconest is appropriate for your child. Additional supervision of your child is required to detect symptoms of allergic reactions during and after administration.

Use of Ruconest with other medications

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

If you receive tissue plasminogen activator as acute treatment for prevention of blood clots (anticoagulant treatment), do not use Ruconest at the same time.

Pregnancy and breastfeeding

It is not recommended to administer Ruconest during pregnancy or breastfeeding.

If you intend to become pregnant, consult your doctor before using Ruconest.

Driving and operating machines

Do not drive or operate machines if you feel dizzy or have a headache after using Ruconest.

Ruconest contains sodium (19.5 mg per vial)

Patients with low-sodium diets should note that this medication contains 19.5 mg of sodium per vial.

The treatment with Ruconest will be initiated by a specialized doctor in the diagnosis and treatment of hereditary angioedema.

Ruconest must be administered by a healthcare professional until you or your caregiver have received the necessary training and are able to administer Ruconest.

Always use this medication exactly as described in this leaflet or as indicated by your doctor or nurse. Consult your doctor or nurse if you are unsure.

Ruconest is administered through a vein for approximately 5 minutes. Your dose will take effect based on your body weight.

Most of the time, one dose is sufficient. An additional dose may be administered if your symptoms do not improve after 120 minutes (for adults and adolescents) or 60 minutes (for children). No more than two doses, calculated according to step 7, may be administered within a 24-hour period.

You or your caregiver may only inject Ruconest after receiving the necessary instructions and training from your doctor or nurse.

Instructions for use

Do not mix or administer Ruconest with other medications or solutions. The following describes how to prepare and administer the Ruconest solution.

Before starting

•Ensure that the packaging is intact and contains all the components specified in section 6 of this leaflet.

• In addition to the packaging, the following is required:

• A tourniquet
• Adhesive tape to secure the needle

• Inspect the vials and other components.

• All vials must be sealed with a plastic cap and an aluminum stopper without visible damage, such as cracks in the glass.
• Check the expiration date. Do not use any component of the kit after the expiration date indicated on the large outer packaging.

On a single box, the different components may have different expiration dates. The expiration date on the large outer packaging reflects the date of the component with the shortest validity period.

• Wait until the required number of powder and solvent vials according to step 1 reach room temperature.

Preparing the solution

Step 1:Cleaning and other requirements

• Wash your hands thoroughly.

• Place the required powder and solvent vials on a flat and clean surface.

• Body weight of 42 kg or less: 1 vial of powder and 1 vial of solvent
• Body weight greater than 42 kg: 2 vials of powder and 2 vials of solvent

•Place the adapter vials on the work surface. Do not remove the packaging from the adapters.

• 2 adapters for 1 vial of powder and 1 vial of solvent
• 4 adapters for 2 vials of powder and 2 vials of solvent

• Place the syringes on the work surface. Do not remove the packaging from the syringes.

• 1 syringe for 1 vial of powder and 1 vial of solvent
• 2 syringes for 2 vials of powder and 2 vials of solvent

Step 2:Disinfecting the stoppers of the vials

• Remove the pressure-sensitive plastic cap from the vials of powder and solvent.

• Use an alcohol wipe to disinfect all the stoppers of the vials and wait at least 30 seconds until the stoppers are dry.

• After disinfection, do not touch the stoppers with your hands or any object.

Step 3:Mounting the adapters on the vials

•Hold one sealed adapter with one hand and remove the cap. The adapter must remain in its plastic packaging.

• Place the adapter on a vial of powder and pierce the stopper until it is attached to the neck of the vial.

• Leave the adapter packaging until you connect the syringe according to steps 4 and 5.
• Repeat the previous steps to mount an adapter on the solvent vial. All adapters provided in the packaging are identical.
• If you need to use a second vial of powder and solvent, repeat the previous steps.

Step 4:Extracting solvent

• Extract a sterile syringe from its packaging.

• Remove the packaging from the adapter of the solvent vial.

•Hold the adapter with one hand. With the other hand, attach the syringe and turn it to the left until it stops to secure it.

•Invert the solvent vial along with the adapter and syringe. While holding it in a vertical position, slowly inject 14 ml of solvent.

If bubbles form, you must minimize them as much as possible. To do this, give a gentle touch to the syringe and exert a gentle pressure pushing the plunger in the syringe. Continue filling the syringe until you reach 14 ml of solvent.

• To disconnect the syringe from the adapter, turn to the left.

• Leave the remaining solvent in the vial and discard the vial.

• Place the syringe on the work surface and make sure not to touch the surface or any other object with the tip of the syringe.

Step 5:Adding solvent to powder and dissolving

• Remove the packaging from the adapter of the powder vial.

• Take the syringe with solvent that you prepared in step 4.

•Hold the adapter with the other hand and attach the syringe. To hold the syringe securely, turn it to the right until it stops.

•Slowly inject the solvent with a single movement to introduce it into the powder vial and minimize foam formation.

• Leave the syringe in the adapter and carefully turn the vial for approximately half a minute. Do not shake it.

After turning, leave the vial on the surface for several minutes until the solution is transparent. If there is undissolved powder, repeat the procedure.

•Repeat steps 4 and 5 if you need to prepare a second solution.

Step 6:Checking prepared solutions

•Check if the powder in the vials has completely dissolved and if the plunger is at the bottom of the syringe.

• Once the powder is dissolved, the solution must be transparent and colorless.

•Do not use the prepared solution if it is turbid, contains particles, or has changed color. Inform the healthcare professional in this case. A small amount of foam formation is acceptable.

Step 7:Extracting the prepared solution

• Calculate the milliliters of prepared solution to be injected.

•Inject the calculated volume of prepared solution while holding the syringe in a vertical position. If you have prepared:

- one vial with a solution, extract the calculated volume

-two vials and your body weight is less than 84kg, extract a similar amount:

a) 14ml from the first vial

b) from the second vial, the difference between the calculated volume and the 14ml from the first vial

- two vials and your body weight is 84 kg or more, extract 14 ml from each vial in each syringe

If bubbles form, you must minimize them as much as possible. To do this, give a gentle touch to the syringe and exert a gentle pressure pushing the plunger in the syringe. Continue filling the syringe until you reach the required volume.

• Do not exceed 14 ml in any case.

• To release the syringe, turn it to the left and discard the vials along with the adapter.

•Place the syringe on the work surface and make sure not to touch the surface or any other object with the tip of the syringe.

Step 8:Checking prepared syringes

• Recheck if the volume of the prepared syringes in step 7 is correct.

Administration through a vein

It is very important that the prepared solution is injected directly into a vein and not into an artery or surrounding tissue.

Inject the Ruconest solution immediately after preparation, preferably while seated.

Step 9:Required components

• Check if all the necessary components are on the work surface:

- 1 or 2 syringes with the prepared solution

- 1 infusion set with a 25 G needle

- 1 alcohol wipe

- 1 non-woven sterile gauze

- 1 adhesive bandage

- 1 tourniquet

- 1 adhesive tape to secure the needle

Step 10:Preparing the infusion set

• Remove the stopper from the threaded end of the infusion set. This is the end without a needle.

•Hold this end with one hand, attach the syringe tip, and secure it by turning to the right until it stops.

•Hold the syringe with the tip upwards. Gently press the plunger of the syringe to carefully fill the infusion set with the prepared solution.

• Check that there is no air in the syringe, infusion set, or needle.

Step 11:Preparing the injection site

•Place the tourniquet on the injection site, preferably in the central part of the upper arm. Compress the vein by tightening the tourniquet. You can achieve this by clenching your fist.

• Palpate with the other hand the suitable vein.

• Disinfect the injection site well with an alcohol wipe and let the skin dry.

Step 12:Administering the prepared solution

• Remove the protective cover from the needle.

• Insert the needle of the infusion set, at the most flat angle possible, into the vein.

• Hold the needle with the adhesive bandage, approximately 7 cm long, over the needle wings.

•Slowly pull back gently on the plunger of the syringe until you see blood enter the tube to ensure that the needle is in the vein.

• Release the tourniquet.

•If there is no blood in the tube, remove the needle, repeat all the steps from step 11, and reinsert the needle.

•If there is blood, inject the solution carefully into the vein, as shown in the image. Inject for approximately 5 minutes.

• If you have prepared two syringes:

- Double the tube near the connector of the infusion set to prevent backflow

- Remove the empty syringe from the infusion set and replace it immediately with the second syringe.

- Deploy the tube and inject the solution carefully in a similar manner to the first syringe.

Step 13:After administration

• Remove the adhesive bandage that secures the needle and remove the needle from the vein.

•Immediately after removing the needle,pressthe sterile gauze over the injection site for a few minutes to reduce bleeding.

• Next, place the adhesive bandage on the injection site.

• Place the yellow protective cover over the needle.

•Dispose of the used infusion set with the needle, unused solution, syringe, and empty vial in an appropriate waste container, as these materials may cause injury if not disposed of properly. Do not reuse the equipment.

Step 14:Documenting administration

Record the following (for example, in your diary):

• Administration date and time

• Batch number printed on the powder vial label

If you use more Ruconest than you should

Contact your doctor or the nearest hospital.

If you have any other questions about using this medication, ask your doctor.

Like all medications, this medication may produce adverse effects, although not all people may experience them.

If your symptoms worsen and/or you present with hives, tingling, difficulty breathing, or swelling of the face or tongue, seek medical attentionimmediately. These symptoms may indicate that you have developed an allergy to Ruconest.

During treatment with Ruconest, some side effects may appear:

Frequent: may affect up to 1 in 10 people

• Nausea

Less frequent: may affect up to 1 in 100 people

• Abdominal pain, diarrhea
• Sensation of tingling, pinpricks, or numbness of the mouth

• Headache, dizziness
• Decreased sense of touch or sensitivity in the skin or extremities
• Throat irritation
• Urticaria (hives)
• Swelling of the ears or the area around the ears

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label after EXP. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C.

Store the vial of powder in the vial box to protect it from light.

Before administering Ruconest, it must be dissolved in the solvent included in the packaging (see section 3). Once reconstituted, the product must be used immediately.

Do not use this medication if, after dissolution, you observe that the solution contains particles or if the solution is discolored. The formation of foam is acceptable in small quantities.

Composition of Ruconest

Vial of powder:

• The active ingredient is conestat alfa. A vial of powder contains 2100 units (U) of conestat alfa. This is equivalent to 2100 units per 14 ml after reconstitution, or a concentration of 150 units/ml.
• The other components are sucrose, sodium citrate (E331) and citric acid.

Vial of solvent:

• The solvent ingredient is water for injection.

Appearance of the product and contents of the package

Ruconest is presented in a single glass vial containing a white to off-white powder for injectable solution, as well as a glass vial with a colourless transparent solvent for dissolving the powder. After dissolving the powder in water for injection, the solution is transparent and colourless.

Ruconest is supplied as a kit in a box containing:

• 1vial of 2100U of powder
• 1vial of 20ml of solvent
• 2adapter for vials
• 1syringe
• 1infusion set with a 35cm tube and a 25 G needle
• 2alcohol wipes
• 1sterile non-woven gauze
• 1adhesive plaster

Marketing authorization holder and manufacturer responsible

Marketing authorization holder:

Pharming Group N.V.

Darwinweg 24

2333 CR Leiden

Netherlands

Manufacturer responsible:

Pharming Technologies B.V.

Darwinweg 24

2333 CR Leiden

Netherlands

Last review date of this leaflet:

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

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This information is intended solely for healthcare professionals:

POSOLGY AND ADMINISTRATION

Dosage

Body weight up to 84 kg

• One intravenous injection of 50 U/kg of body weight.

Body weight of 84 kg or more

• One intravenous injection of 4200 U (two vials).

In most cases, a single injection of Ruconest is sufficient for the treatment of an acute angioedema crisis.

If the clinical response is insufficient, a second dose (50 U/kg of body weight up to 4200 U) may be administered.

No more than two doses may be administered within a 24-hour period.

Dosage calculation

Determine the patient's body weight.

Body weight up to 84 kg

• In patients weighing up to 84 kg, the administration volume required will be calculated using the following formula:

Body weight of 84 kg or more

• In patients weighing 84 kg or more, the administration volume required is 28 ml, equivalent to 4200 U (two vials).

Reconstituteeach vialwith 14 ml of water for injection (see Reconstitution section below).

The reconstituted solution in each vial contains 2100 U of conestat alfa at 150 U/ml.

The required volume of the reconstituted solution should be administered via intravenous injection over approximately 5 minutes.

SPECIAL PRECAUTIONS FOR DISPOSAL AND OTHER HANDLING

Preparation and handling

Each vial of Ruconest is for single use only.

Ruconest should be administered intravenously after reconstitution with water for injection. Aseptic technique should be used for reconstitution, combination, and mixing of solutions.

Reconstitution

1. Each vial of Ruconest (2100 U) should be reconstituted with 14 ml of water for injection.
2. Disinfect the rubber stoppers of the powder and solvent vials, and attach an adapter to each vial of solvent and powder to connect it to the vial neck.
3. Attach the syringe to the solvent vial adapter and turn it to the right until it clicks. To release the syringe from the adapter, turn it to the left and discard the vial along with the adapter.
4. Attach the solvent vial syringe to the powder vial adapter and turn it to the right until it clicks. The solvent should be added slowly to avoid a strong impact on the powder and mix gently to minimize foam formation in the solution. Leave the syringe in the adapter. Repeat steps 3 and 4 if you need to prepare a second solution (this requires a second pack).
5. The reconstituted solution contains150U/ml of conestat alfa and is a colourless transparent solution.The reconstituted solution in each vial should be inspected for particles and colour changes. Do not use a solution that presents particles or colour changes. Small amounts of foam are acceptable. This medicine should be used immediately.

Administration

1. Inject the required volume of the prepared solution. Do not exceed 14 ml per syringe. To release the syringe, turn it to the right and discard the vial along with the adapter.
2. Attach the infusion set to the syringe and turn it to the right to lock it. Hold the syringe with the tip upwards and gently press the plunger to fill the infusion set with solution.
3. Disinfect the injection site with analcohol wipe. Remove the needle cover from the infusion set and carefully insert the needle into the vein.
4. Ensure the tourniquet is released. Inject the solution into the vein over approximately 5 minutes.
5. If preparing two syringes, double the tube to prevent backflow, loosen the empty syringe from the infusion set (to the left) and immediately replace it with the second syringe. Inject the solution from the second syringe carefully.

Disposal

Dispose of the used infusion set with needle, unused solution, syringe, and empty vial safely in an appropriate medical waste container, as these materials may cause injury if not disposed of properly. Do not reuse the equipment.