Prospect: information for the user

Cinryze 500UI powder and solvent for injectable solution
Human C1 esterase inhibitor

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

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• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you, 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 or pharmacist, even if they are not listed in this prospect. See section 4.

1.What is Cinryze and what it is used for

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

3.How to use Cinryze

4.Possible adverse effects

5.Storage of Cinryze

6.Contents of the package and additional information

Cinryze contains the human protein called “C1 esterase inhibitor” as the active ingredient.

The C1 esterase inhibitor is a protein that is produced naturally and is normally present in the blood. If the level of C1 esterase inhibitor in the blood is low or the C1 esterase inhibitor does not function properly, an episode of swelling (called angioedema) may occur. Symptoms may include:

• swelling of hands and feet
• swelling of face, eyelids, lips, or tongue
• swelling of the larynx, which may make it difficult to breathe
• genital swelling

In adults and children, Cinryze can increase the amount of C1 esterase inhibitor in the blood and either prevent (before undergoing a medical or dental procedure) or stop these episodes of swelling from occurring.

In adults, adolescents, and children (6 years of age and older), Cinryze can increase the amount of C1 esterase inhibitor in the blood and prevent episodes of swelling from occurring on a regular basis.

No use Cinryze

• If you are allergic to the human C1 esterase inhibitor or to any of the other components of this medication (listed in section 6). It is essential to inform your doctor if you believe you have ever had an allergic reaction to any of the components of Cinryze.

Warnings and precautions

• Before starting treatment with Cinryze, it is essential to inform your doctor if you have, or have had, blood clotting problems (thrombotic events). In this case, you will be closely monitored.
• If you start to experience skin rashes, chest tightness, wheezing, or rapid heartbeat after using Cinryze, inform your doctor immediately. See section 4.
• When medications are made from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include the careful selection of plasma and blood donors to ensure that individuals with a risk of being carriers of infections are excluded, and the analysis of each donation and plasma mixture to detect signs of viruses/infections. Manufacturers of these products also include measures in the processing of blood or plasma that may inactivate and/or eliminate viruses. Despite these measures, when administering medications made from human blood or plasma, it cannot be completely ruled out that an infection may be transmitted. This also applies to unknown or emerging viruses, or other types of infections.

• The measures taken are considered effective for viruses such as the human immunodeficiency virus (HIV), hepatitis B and C viruses, and for non-encapsulated hepatitis A and parvovirus B19 viruses.

• Your doctor may recommend that you consider vaccinating against hepatitis A and B if you regularly or repeatedly receive products of the human C1 esterase inhibitor made from human plasma.

• To improve the traceability of biological medications, the doctor or nurse must clearly record the name and batch number of the administered medication.

Children

Cinryze should not be used in children under 6 years of age for routine prevention of angioedema crises.

Use of Cinryze with other medications

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you believe you may be pregnant or intend to become pregnant, consult your doctor before using this medication. The information on the safety of using Cinryze in pregnant women and breastfeeding women is limited. Your doctor will inform you about the risks and benefits of using this medication.

Driving and operating machinery

The influence of Cinryze on the ability to drive and operate machinery is small.

Cinryze contains sodium

This medication contains 11.5 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 0.5% of the maximum daily sodium intake recommended for an adult.

Your treatment will be initiated and monitored under the supervision of a doctor with experience in caring for patients with hereditary angioedema (HAE).

Your doctor or nurse may prepare and administer the Cinryze injection to you. If your doctor decides that you can self-administer the medication, your doctor or nurse will teach you or a family member how to prepare and inject Cinryze. Your doctor will periodically review the preparation and administration process with you or a family member or caregiver.

The recommended dose of Cinryze for adults, adolescents, children, elderly patients, or patients with liver or kidney problems is as follows:

Use in adults and adolescents (12 years of age and older)

Treatment of swelling episodes

• A dose of 1000 UI (two vials) of Cinryze should be injected with the first sign of a swelling episode.
• A second injection of 1000 UI may be administered if symptoms do not improve after 60 minutes.
• If a severe crisis occurs, especially laryngeal edema, or if treatment is delayed, a second dose of 1000 UI may be administered before 60 minutes have passed since the first dose, depending on your clinical response.
• Cinryze will be administered intravenously (into a vein).

Routine prevention of swelling episodes

• A dose of 1000 UI (two vials) of Cinryze should be injected every 3 or 4 days for routine prevention of swelling episodes.
• Your doctor may adjust the administration interval based on your response to Cinryze.
• Cinryze will be administered intravenously (into a vein).

Preoperative prevention of swelling episodes

• A dose of 1000 UI (two vials) of Cinryze should be injected up to 24 hours before a medical, dental, or surgical procedure.
• Cinryze will be administered intravenously (into a vein).

Use in children

Reconstitution and administration

Normally, your doctor or nurse will administer the Cinryze injection into a vein (intravenously). You or your caregiver may also be responsible for administering Cinryze by injection, but only after receiving proper training. If you administer Cinryze yourself, always follow your doctor's instructions exactly. If you are unsure, ask your doctor. If your doctor decides that you can receive home treatment, they will provide detailed instructions.You will be asked to keep a diary to document each treatment administered at home and bring it to each of your doctor's appointments. You/your caregiver will undergo periodic reviews of the injection technique to ensure that you handle the medication properly.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

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

This may include allergic reactions.

Inform your doctorimmediatelyif you experience any of the following symptoms after using this medication. Although rare, symptoms can be severe.

Sudden wheezing, difficulty breathing, swelling of the eyelids, face, or lips, skin rash or itching (especially when affecting the entire body).

Very Common Adverse Effects(may affect more than 1 in 10people): headache, nausea.

Common Adverse Effects(may affect up to 1 in 10people): hypersensitivity, dizziness, vomiting, skin rash, itching or redness, rash or pain at the injection site, fever.

Rare Adverse Effects(may affect up to 1 in 100people): high blood sugar levels, blood clots, pain in the veins, hot flashes, cough, stomach pain, diarrhea, skin peeling, swelling and pain in the joints, muscle pain, and chest discomfort.

It is expected that adverse effects in children and adolescents will be similar to those of adults.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or nurse, evenif it ispossibleadverse effects that do not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es. 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 Cinryze after the expiration date that appears on the box and on the vials after “CAD”.

Store below 25°C. Do not freeze. Store in the original packaging to protect it from light.

Once reconstituted, the Cinryze solution must be used immediately.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment.

Composition ofCinryze

The active ingredient is the human C1 esterase inhibitor prepared from human plasma donors. Each vial of powder contains 500UI human C1 esterase inhibitor. After reconstitution, a vial contains 500UI human C1 esterase inhibitor per 5ml, which corresponds to a concentration of 100UI/ml. Two vials of reconstituted Cinryze contain 1000 UI human C1 esterase inhibitor per 10 ml, which corresponds to a concentration of 100UI/ml.

The total protein content of the reconstituted solution is 15±5mg/ml.

One international unit (UI) is equivalent to the amount of human C1 esterase inhibitor present in 1ml of normal human plasma.

The other components are sodium chloride, sucrose, sodium citrate, L-valine, L-alanine, and L-threonine (see section2).

Vehicle: injectable water

Appearance of the product and contents of the package

Powder and injectable water for solution.

Cinryze is a white powder that comes in a vial.

After dissolving in injectable water, the solution is transparent and colorless to slightly blue.

Each package contains:
2 vials of Cinryze 500UI powder for injectable solution
2 vials of injectable water (5ml each)

2 filter transfer devices

2 disposable 10ml syringes

2 venipuncture sets

2 protectors

Use only a silicone-free syringe (provided in the package) for administering the medication.

Marketing authorization holder and manufacturer

Takeda Manufacturing Austria AG

Industriestrasse 67

1221 Vienna

Austria

For more information about this medication, please contact the local representative of the marketing authorization holder:

Takeda Farmacéutica España S.A

Tel: +34 917 90 42 22

[email protected]

Last review date of this leaflet: 09/2022

Other sources of information

Detailed information about this medication is available on the European Medicines Agency website:http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan drugs.

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This information is intended only for healthcare professionals:

Reconstitution and administration of Cinryze

The reconstitution, administration of the product, and handling of the administration equipment and needles should be performed with caution.

Use the filter transfer device provided with Cinryze or a commercially available double-ended needle.

Use only a silicone-free syringe (provided in the package) for administering the medication.

Preparation and handling

Cinryze is indicated for intravenous (in the vein) administration after reconstitution with injectable water.

The Cinryze vial is for single use only.

Reconstitution

For a dose of 500 UI: 1 vial of powder, 1 vial of vehicle, 1 filter transfer device, 1 disposable 10 ml syringe, 1 venipuncture set, and 1 protector are needed. Save the remaining vial and equipment for the next dose.

For a dose of 1000 UI: 2 vials of powder, 2 vials of vehicle, 2 filter transfer devices, 1 disposable 10 ml syringe, 1 venipuncture set, and 1 protector are needed.

Each vial of product should be reconstituted with 5ml of injectable water.

One vial of reconstituted Cinryze corresponds to a dose of 500 UI. Therefore, reconstitute only one vial of Cinryze for a dose of 500 UI.

Two vials of reconstituted Cinryze correspond to a dose of 1000 UI. Therefore, for a dose of 1000UI, two vials are combined.

1. Work on the provided protector and wash your hands before performing the following procedures.
2. Use aseptic technique during the reconstitution procedure.
3. Ensure that the vial of powder and the vial of vehicle are at room temperature (15°C‑25°C).
4. Remove the label from the vial of powder along the perforated lines that indicate the inverted triangle.
5. Remove the seals from the vials of powder and vehicle.
6. Clean the stoppers with a disinfectant wipe and let them dry before use.
7. Remove the seal from the top of the filter transfer device package.

Do not remove the device from the package.

1. Note: the filter transfer device should be attached to the vehicle vial before being attached to the powder vial, so as not to lose the vacuum in the powder vial. Place the vehicle vial on a flat surface and insert the blue end of the filter transfer device into the vehicle vial, pushing it in until the point penetrates the center of the vehicle vial stopper and the device fits in place. The filter transfer device should be vertical before penetrating the stopper.

1. Remove the seal from the filter transfer deviceand discard it. Be careful not to touch the exposed end of the filter transfer device.

1. Place the powder vial on a flat surface. Invert the filter transfer deviceand the vehicle vial that contains the injectable water, and insert the transparent end of the filter transfer deviceinto the powder vial, pushing it in until the point penetrates the rubber stopper and the filter transfer device fits in place. The filter transfer deviceshould be vertical before penetrating the powder vial stopper. The vacuum of the powder vial will extract the vehicle. If the vial does not have a vacuum, do not use the product.

1. Movely the powder vial carefully until it is well dissolved. Do not shake the powder vial. Ensure that all the powder is dissolved.

1. Disconnect the vehicle vial by turning it to the left. Do not remove the transparent end of the filter transfer devicefrom the powder vial.

One vial of reconstituted Cinryze contains 500UI human C1 esterase inhibitor in 5ml, resulting in a concentration of 100UI/ml. Proceed to the administration process if patients receive a dose of 500UI.

Two vials of powder of Cinryze should be reconstituted to make a dose (1000UI/10ml). Therefore, repeat steps 1 to 12 above, using a new package with a filter transfer device to reconstitute the second vial of powder. Do not reuse the same filter transfer device.Once the two vials have been reconstituted, proceed to the administration process for a dose of 1000 UI.

Administration process for a dose of 500 UI

1. Use aseptic technique during the administration procedure.
2. After reconstitution, the Cinryze solutions are colorless to slightly blue and transparent. Do not use the product if the solutions are turbid or colored.
3. With a sterile and disposable 10ml syringe, pull the plunger to draw approximately 5ml of air into the syringe.

1. Attach the syringe to the top of the transparent end of the filter transfer deviceturning it to the right.

1. Invert the vial carefully and inject air into the solution and then slowly extract the reconstituted Cinryze solution from the vial into the syringe.

1. Disconnect the syringe from the vial by turning it to the left and releasing it from the transparent end of the filter transfer device.

1. Before administration, inspect the reconstituted Cinryze solution for particles. Do not use the medication if particles are observed.
2. Attach the venipuncture set to the syringe containing the Cinryze solution and administer the injection intravenously (in the vein) to the patient. Administer 500UI (reconstituted in 5ml of injectable water) of Cinryze by intravenous injection at a rate of 1ml per minute for 5minutes.

Administration process for a dose of 1000 UI

1. Use aseptic technique during the administration procedure.
2. After reconstitution, the Cinryze solutions are colorless to slightly blue and transparent. Do not use the product if the solutions are turbid or colored.
3. With a sterile and disposable 10ml syringe, pull the plunger to draw approximately 5ml of air into the syringe.

1. Attach the syringe to the top of the transparent end of the filter transfer deviceturning it to the right.

1. Invert the vial carefully and inject air into the solution and then slowly extract the reconstituted Cinryze solution from the vial into the syringe.

1. Disconnect the syringe from the vial by turning it to the left and releasing it from the transparent end of the filter transfer device.

1. Using the same syringe, repeat steps 3 to 6 with the second vial of reconstituted Cinryze to make a complete dose of 10ml.
2. Before administration, inspect the reconstituted Cinryze solution for particles. Do not use the medication if particles are observed.
3. Attach the venipuncture set to the syringe containing the Cinryze solution and administer the injection intravenously (in the vein) to the patient. Administer 1000UI (reconstituted in 10ml of injectable water) of Cinryze by intravenous injection (in the vein) at a rate of 1ml per minute for 10minutes.

Disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.