Cinryze 500 units powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Cinryze 500 IU powder and solvent for injection solution

human C1 esterase inhibitor

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Cinryze is and what it is used for
2. What you need to know before using Cinryze
3. How to use Cinryze
4. Possible side effects
5. How to store Cinryze
6. Contents of the pack and other information

1. What Cinryze is and what it is used for

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

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

• hands and feet
• face, eyelids, lips or tongue
• larynx, which may make it difficult to breathe
• genitals

In adults and children, Cinryze can increase the amount of C1 esterase inhibitor in the blood and either prevent (prior to undergoing a medical or dental procedure) such swelling episodes from occurring or help control them once they have started.

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

2. What you need to know before using Cinryze

Do not use Cinryze

• if you are allergic to human C1 esterase inhibitor or to any of the other ingredients of this medicine (listed in section 6). It is important that you inform your doctor if you think you have ever had an allergic reaction to any of the components of Cinryze.

Warnings and precautions

• Before starting treatment with Cinryze, it is important that you inform your doctor if you have or have had blood clotting problems (thrombotic events). In such cases, you will be closely monitored.

• If you develop skin rashes, chest tightness, wheezing, or rapid heartbeat after using Cinryze, inform your doctor immediately. See section 4.

• When medicines are prepared from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include the careful selection of blood and plasma donors to exclude individuals at risk of carrying infections, and testing each donation and plasma pool for signs of viruses/infections. Manufacturers of these products also include steps in the processing of blood or plasma that can inactivate and/or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown or emerging viruses or other types of infections.

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

• Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly or repeatedly receive human plasma-derived C1 esterase inhibitor products.

• In order to improve traceability of biological medicines, your doctor or nurse should clearly record the name and batch number of the medicine administered.

Children

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

Use of Cinryze with other medicines

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Information regarding the safety of using Cinryze in pregnant or breastfeeding women is limited. Your doctor will advise you about the risks and benefits of using this medicine.

Driving and using machines

The influence of Cinryze on the ability to drive and use machines is minor.

Cinryze contains sodium

This medicine contains 11.5 mg of sodium (main component of table/cooking salt) per vial. This corresponds to 0.5% of the maximum daily recommended sodium intake for an adult.

3. How to use Cinryze

Your treatment will be initiated and supervised by a physician experienced in the management of patients with hereditary angioedema (HAE).

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

• You should receive a dose of 1,000 IU (two vials) of Cinryze at the first sign of a swelling episode.
• A second 1,000 IU injection may be given if symptoms do not improve after 60 minutes.
• In the case of a severe attack, especially swelling of the glottis (larynx), or if treatment initiation is delayed, the second 1,000 IU dose may be administered before 60 minutes have elapsed after the first dose, depending on your clinical response.
• Cinryze is administered intravenously (into the vein).

Routine prevention of swelling episodes

• You should receive a dose of 1,000 IU (two vials) of Cinryze every 3 or 4 days for routine prevention of swelling episodes.
• Your doctor may adjust the dosing interval based on your response to Cinryze.
• Cinryze is administered intravenously (into the vein).

Preoperative prevention of swelling episodes

• You should receive a dose of 1,000 IU (two vials) of Cinryze up to 24 hours before a medical, dental, or surgical procedure.
• Cinryze is administered intravenously (into the vein).

Use in children

Reconstitution and Administration Instructions

Cinryze will normally be administered by your doctor or nurse as an intravenous injection (into a vein). You or your caregiver may also administer Cinryze by injection, but only after receiving appropriate training. If you are to administer Cinryze yourself, always follow your doctor's instructions exactly. If in doubt, consult your doctor. If your doctor decides that you may receive treatment at home, you will be given detailed instructions. You will be asked to keep a diary to document each treatment administered at home and to bring this diary to every appointment with your doctor. You/your caregiver will undergo periodic reviews of the injection technique to ensure the medicine is being handled properly.

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

4. Possible adverse effects

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

This may include allergic-type reactions.

Inform your doctor immediately if you experience any of the following symptoms after using this medicine. Although rare, these symptoms may be severe.

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

Very common adverse effects (may affect more than 1 in 10 people): headache, nausea.

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

Uncommon adverse effects (may affect up to 1 in 100 people): high blood sugar levels, blood clots, vein pain, hot flushes, cough, stomach pain, diarrhea, skin peeling, joint swelling and pain, muscle pain and chest discomfort.

Adverse effects in children and adolescents are expected to be similar to those in adults.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Cinryze

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

Do not use this medicine after the expiry date stated on the carton and on the vials after "EXP".

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

After reconstitution, the Cinryze solution must be used immediately.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Cinryze

The active substance is human C1 esterase inhibitor, prepared from plasma of human donors. Each vial of powder contains 500 IU of human C1 esterase inhibitor. After reconstitution, one vial contains 500 IU of human C1 esterase inhibitor per 5 ml, corresponding to a concentration of 100 IU/ml. Two vials of reconstituted Cinryze contain 1,000 IU of human C1 esterase inhibitor per 10 ml, corresponding to a concentration of 100 IU/ml.

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

One International Unit (IU) is equivalent to the amount of C1 esterase inhibitor present in 1 ml of normal human plasma.

The other components are sodium chloride, sucrose, sodium citrate, L-valine, L-alanine and L-threonine (see section 2).

Solvent: Water for injections.

Appearance of the product and contents of the pack

Powder and solvent for injectable solution.

Cinryze is a white powder supplied in a vial.

After dissolution in water for injections, the solution is clear and colourless to slightly blue.

Each pack contains:

• 2 vials of Cinryze 500 IU powder for injectable solution
• 2 vials of water for injections (5 ml each)
• 2 transfer devices with filter
• 2 disposable 10 ml syringes
• 2 venous access sets
• 2 protective caps

Use only a silicone-free syringe (provided in the pack) for administration of the medicine.

Marketing Authorisation Holder

Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria

Manufacturer

Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria

Shire International Licensing B.V.
Mercuriusplein 11
2132 HA Hoofddorp
The Netherlands

More information about this medicine is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: https://www.ema.europa.eu. Links to other websites on rare diseases and orphan medicines are also available.

This information is intended for healthcare professionals only:

Reconstitution and administration of Cinryze

Reconstitution, product administration, and handling of administration equipment and needles must be performed with caution.

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

Use only a non-siliconized syringe (supplied in the pack) for administration of the medicine.

Preparation and handling

Cinryze is indicated for intravenous administration (into the vein) after reconstitution with water for injections.

The Cinryze vial is for single use only.

Reconstitution

For a 500 IU dose: 1 vial of powder, 1 vial of solvent, 1 transfer device with filter, 1 disposable 10 ml syringe, 1 venipuncture set, and 1 tray are required. Keep the remaining vial and administration equipment for the next dose.

For a 1,000 IU dose: 2 vials of powder, 2 vials of solvent, 2 transfer devices with filter, 1 disposable 10 ml syringe, 1 venipuncture set, and 1 tray are required.

Each vial of product must be reconstituted with 5 ml of water for injections.

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

Two reconstituted vials of Cinryze correspond to a 1,000 IU dose. Therefore, for a 1,000 IU dose, two vials are combined.

1. Work on the tray provided and wash your hands before performing the following procedures.
2. Use an aseptic technique during the reconstitution procedure.
3. Ensure that the powder vial and solvent vial are at room temperature (15°C – 25°C).
4. Remove the label from the powder vial by peeling off the purple strip indicating the arrow.
5. Remove the caps from the powder and solvent vials.
6. Clean the stoppers with a disinfectant wipe and allow them to dry before use.
7. Remove the seal from the top of the transfer device package. Do not remove the device from the package.

1. Note: the transfer device must be attached to the solvent vial before being attached to the powder vial, so that the vacuum in the powder vial is not lost. Place the solvent vial on a flat surface and insert the blue end of the transfer device into the solvent vial, pushing it in until the spike penetrates the center of the vial stopper and the device clicks into place. The transfer device must be vertical before piercing the stopper.

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

1. Place the powder vial on a flat surface. Invert the transfer device and the solvent vial containing water for injections, and insert the transparent end of the transfer device into the powder vial, pushing it in until the spike penetrates the rubber stopper and the transfer device clicks into place. The transfer device must be vertical before piercing the powder vial stopper. The vacuum in the powder vial will draw in the solvent. If the vial has no vacuum, do not use the product.

1. Gently swirl the powder vial until the powder is completely dissolved. Do not shake the powder vial. Ensure that all powder is fully dissolved.

1. Disconnect the solvent vial by turning it to the left. Do not remove the transparent end of the transfer device from the powder vial.

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

Two vials of Cinryze powder must be reconstituted to prepare a dose (1,000 IU/10 ml). Therefore, repeat steps 1 to 12 above, using a new transfer device package to reconstitute the second powder vial. Do not reuse the same transfer device. Once both vials have been reconstituted, proceed to the administration process for a 1,000 IU dose.

Administration process for a 500 IU dose

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

1. Attach the syringe to the top of the transparent end of the transfer device by turning it to the right.

1. Carefully invert the vial, inject air into the solution, and then slowly withdraw the reconstituted Cinryze solution into the syringe.

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

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

Administration process for a 1,000 IU dose

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

1. Attach the syringe to the top of the transparent end of the transfer device by turning it to the right.

1. Carefully invert the vial, inject air into the solution, and then slowly withdraw the reconstituted Cinryze solution into the syringe.

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

1. Using the same syringe, repeat steps 3 to 6 with the second reconstituted Cinryze vial to obtain a complete 10 ml dose.
2. Before administration, inspect the reconstituted Cinryze solution for particles. Do not use the medicine if particles are observed.
3. Attach the venipuncture set to the syringe containing the Cinryze solution and administer the injection intravenously (into the vein) to the patient. Administer 1,000 IU (reconstituted in 10 ml of water for injections) of Cinryze by intravenous injection (into the vein) at a rate of 1 ml per minute over 10 minutes.

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