CINRYZE Powder and solvent for solution for injection Ref.[6464] Active ingredients: C1-inhibitor

Cinryze therapy should be initiated under supervision of a physician experienced in the care of patients with hereditary angioedema (HAE).

Posology

Adult

Treatment of angioedema attacks:

• 1000 IU of Cinryze at the first sign of the onset of an angioedema attack.
• A second dose of 1000 IU may be administered if the patient has not responded adequately after 60 minutes.
• For patients experiencing laryngeal attacks or if initiation of treatment is delayed, the second dose can be given sooner than 60 minutes.

Routine prevention of angioedema attacks:

• 1000 IU of Cinryze every 3 or 4 days is the recommended starting dose for routine prevention against angioedema attacks; the dosing interval may need to be adjusted according to individual response. The continued need for regular prophylaxis with Cinryze should be reviewed on a regular basis.

Pre-procedure prevention of angioedema attacks:

• 1000 IU of Cinryze within 24 hours before a medical, dental, or surgical procedure.

Paediatric population

Adolescents

For treatment, routine prevention and pre-procedure prevention in adolescents 12 to 17 years old, the dose is the same as for adults.

Children

The safety and efficacy of Cinryze in children less than 2 years old has not been established. Data supporting dosing recommendations in children less than 6 years old are very limited. Currently available data are described in sections 4.8, 5.1, and 5.2.

Elderly patients

No special investigations have been performed. For treatment, routine prevention and pre-procedure prevention in elderly patients, 65 years of age or older, the dose is the same as for adults.

Patients with renal or hepatic impairment

No special investigations have been performed. For treatment, routine prevention and pre-procedure prevention in patients with renal or hepatic impairment, the dose is the same as for adults.

Method of administration

For intravenous use.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.

The reconstituted product should be administered by intravenous injection at a rate of 1 ml per minute.

No case of overdose has been reported.

Shelf life: 2 years.

After reconstitution, the product should be used immediately. However, chemical and physical in-use stability has been demonstrated for 3 hours at room temperature (15°C-25°C).

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

For storage conditions after reconstitution of the medicinal product, see section 6.3.

500 IU of C1 inhibitor in a colourless glass vial (Type I), sealed with a rubber stopper (Type I) and an aluminium seal with a plastic flip-off cap.

5 ml of water for injections in a colourless glass vial (Type I), closed with a rubber stopper (Type I) and an aluminium seal with a plastic flip-off cap.

Each pack contains:

Two powder vials.
Two solvent vials.
2 filter transfer devices, 2 disposable 10 ml syringes, 2 venipuncture sets, and 2 protective mats.

Each kit contains material for either one 1000 IU dose or two 500 IU doses.

Reconstitution and administration of Cinryze

Reconstitution, product administration and handling of the administration set and needles must be done with caution.

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

Preparation and handling:

Cinryze is intended for intravenous administration after reconstitution with water for injections.

Cinryze vial is for single use only.

Reconstitution:

One powder vial, 1 solvent vial, 1 filter transfer device, 1 disposable 10 ml syringe, 1 venipuncture set and 1 protective mat is needed to prepare one dose of 500 IU.

Two powder vials, 2 solvent vials, 2 filter transfer devices, 1 disposable 10 ml syringe, 1 venipuncture set and 1 protective mat is needed to prepare one dose of 1000 IU.

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

One vial of reconstituted Cinryze corresponds to a dose of 500 IU.

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

1. Work on the mat provided and wash your hands before performing the following procedures.
2. Aseptic technique should be used during the reconstitution procedure.
3. Ensure the powder vial and the solvent vial are at room temperature (15°C-25°C).
4. Release the powder vial label by tearing down the perforated strip indicated by the inverted triangle.
5. Remove plastic caps from the powder and solvent vials.
6. Cleanse stoppers with a disinfection swab and allow them to dry prior to use.
7. Remove protective covering from the top of the transfer device package. Do not remove the device from the package.
8. 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 down until the spike penetrates through the centre of the solvent vial stopper and the device snaps in place. The transfer device must be vertical prior to penetrating the stopper closure.
9. Remove the plastic package from the transfer device and discard it. Take care not to touch the exposed end of the transfer device.
10. Place the powder vial on a flat surface. Invert the transfer device and the solvent vial containing water for injections and insert the clear end of the transfer device into the powder vial, pushing down until the spike penetrates the rubber stopper and the transfer device snaps into place. The transfer device must be vertical prior to penetrating the stopper closure of the powder vial. The vacuum in the powder vial will draw in the solvent. If there is no vacuum in the vial, do not use the product.
11. Gently swirl the powder vial until all powder is dissolved. Do not shake the powder vial. Make sure all the powder is completely dissolved.
12. Disconnect the solvent vial by turning it anti-clockwise. Do not remove the clear end of the transfer device from the powder vial.

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

Two vials of Cinryze powder must be reconstituted to make one dose (1000 IU/10 ml). Therefore, repeat instructions 1 to 12 above using an additional package containing a transfer device to reconstitute the second of two powder vials. Do not reuse the transfer device. Once the two vials are reconstituted proceed to administration process for a dose of 1000 IU

Administration process for a dose of 500 IU:

1. Aseptic technique should be used during the administration procedure.
2. After reconstitution, the Cinryze solutions are colourless to slightly blue and clear. Do not use the product if the solutions are turbid or discoloured.
3. Using a sterile, disposable 10 ml syringe, draw back the plunger to allow approximately 5 ml of air into the syringe.
4. Attach the syringe onto the top of the clear end of the transfer device by turning it clockwise.
5. Invert the vial gently and inject air into the solution and then slowly withdraw the reconstituted Cinryze solution into the syringe.
6. Detach the syringe from the vial by turning it anti-clockwise and releasing it from the clear end of the transfer device.
7. Inspect the reconstituted Cinryze solution for particulate matter prior to administration; do not use if particles are observed.
8. Attach the venipuncture set to the syringe containing Cinryze solution and inject intravenously into 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 dose of 1000 IU:

1. Aseptic technique should be used during the administration procedure.
2. After reconstitution, the Cinryze solutions are colourless to slightly blue and clear. Do not use the product if the solutions are turbid or discoloured.
3. Using a sterile, disposable 10 ml syringe, draw back the plunger to allow approximately 5 ml of air into the syringe.
4. Attach the syringe onto the top of the clear end of the transfer device by turning it clockwise.
5. Invert the vial gently and inject air into the solution and then slowly withdraw the reconstituted Cinryze solution into the syringe.
6. Detach the syringe from the vial by turning it anti-clockwise and releasing it from the clear end of the transfer device.
7. Using the same syringe, repeat steps 3 to 6 with a second vial of reconstituted Cinryze to make one complete 10 ml dose.
8. Inspect the reconstituted Cinryze solution for particulate matter prior to administration; do not use if particles are observed.
9. Attach the venipuncture set to the syringe containing Cinryze solution and inject intravenously into the patient. Administer 1000 IU (reconstituted in 10 ml of water for injections) of Cinryze by intravenous injection at a rate of 1 ml per minute over 10 minutes.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.