Voraxaze

Package leaflet: Information for the patient

Voraxaze 1,000 units powder for injectable solution

glucarpidase
This medicinal product is under additional monitoring. This will allow for rapid identification of
new safety information. You can help by reporting any side effects you experience while taking
this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before this medicine is administered to you, as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

1. What Voraxaze is and what it is used for
2. What you or your child should know before being given Voraxaze
3. How Voraxaze is administered
4. Possible side effects
5. How to store Voraxaze
6. Contents of the pack and other information

1. What Voraxaze is and what it is used for

The active substance of this medicine is glucarpidase, an enzyme that breaks down the anticancer medicine methotrexate.
Voraxaze is used in adults and children older than 28 days who have been given methotrexate as anticancer treatment, but whose bodies are unable to eliminate it quickly enough and who are at risk of serious adverse effects. The medicine destroys methotrexate present in the bloodstream, reducing its levels and thereby helping to control adverse effects and prevent their worsening. It works very rapidly and within 15 minutes can reduce the amount of methotrexate in the bloodstream by more than 90%. The medicine does not penetrate cells, so it does not interfere with methotrexate already inside tumor cells and thus does not prevent its anticancer action.

2. What you or your child should know before Voraxaze is administered

Do not take Voraxaze

• if you are allergic to glucarpidase or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor before you are given Voraxaze.
This medicine will be administered to you as soon as possible after your doctor has determined that it is necessary to prevent serious side effects of methotrexate.
This medicine alone cannot prevent or stop all side effects of high-dose methotrexate, and if needed, other treatments and supportive care will also be administered to you.
It is important that your doctor knows the level of methotrexate in your blood and evaluates your kidney function. You will therefore undergo tests before and after treatment with this medicine.

Children and adolescents
This medicine can be administered to children starting from 28 days of age. The safety and efficacy of this medicine in children under 28 days of age have not been established.

Other medicines and Voraxaze
This medicine may affect the levels of folinic acid in your body—a different product that your doctor may administer to reduce methotrexate toxicity. As a precaution, your doctor will adjust the timing of folinic acid administration and the doses of Voraxaze to ensure that at least 2 hours elapse between the two medicines. Your doctor will resume folinic acid administration no sooner than 2 hours after glucarpidase administration.
No other interactions with other medicines have been reported in clinical studies.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor.
Since this medicine is used only in patients who have already received methotrexate—a drug known to cause fetal harm—no studies have been conducted to determine whether this medicine alone could have harmful effects on the fetus during pregnancy or whether it is excreted in breast milk.

Driving and using machines
This medicine has no effect or has a negligible effect on the ability to drive vehicles or operate machinery.

3. How this medicine is administered

This medicine is administered as an injection into a vein, lasting 5 minutes. Your doctor will calculate the appropriate dose for you based on your body weight. The recommended dose is 50 Units per kilogram of body weight.
Since the medicine is given under medical supervision, it is unlikely that you will receive too much.
If you think you have been given more medicine than you should have, inform your doctor or nurse.
You will be monitored to check for changes in the amount of methotrexate in your blood after treatment with this medicine.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Immediately inform your doctor or a healthcare professional if you experience any of the following
symptoms:

• swelling of the throat, tightness in the chest, difficulty breathing
• swelling of hands, feet, face, lips or mouth
• rash with or without flushing and facial swelling
• tremors or chills without fever
  If you have any of the symptoms listed above, you may be experiencing a severe allergic reaction and may require urgent medical treatment. These side effects (allergic reactions) are very rare and, when they occur, usually appear on the day of treatment.

Inform your doctor or a healthcare professional as soon as possible if you experience any of the following side effects, which are rare but have been reported during treatment with this medicine:

• fever
• headache
• tingling or itching sensation on the skin
• burning sensation on the skin
  If you experience any other side effect not mentioned in this leaflet, inform your doctor or a healthcare professional.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor. You can also report side effects directly (see details below). By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Voraxaze

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 vial after
Exp. The expiry date refers to the last day of that month.
This medicine will be administered to you under medical supervision. The medicine should be stored
at a temperature between 2 °C and 8 °C and must not be frozen.
Date of use: This medicine must not be used after the expiry date indicated on the vial and outer carton.
The pharmacist will check the expiry date before the medicine is dispensed.

6. Package contents and other information

What Voraxaze contains
The active substance is glucarpidase.
The other components are: lactose, tromethamine, and zinc acetate dihydrate.

Description of the appearance of Voraxaze and contents of the pack
Each pack contains one vial with a white or almost white lyophilized powder for reconstitution with 1 mL of sterile 0.9% sodium chloride solution (not included).

Marketing Authorisation Holder and manufacturer
Name and address of the Marketing Authorisation Holder
SERB SAS
40 Avenue George V
75008 Paris
France

Name and address of the manufacturer(s) responsible for batch release
Almac Pharma Services Limited
Seagoe Industrial Estate,
Portadown,
Craigavon,
BT63 5UA, United Kingdom (Northern Ireland)

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/

The following information is intended exclusively for healthcare professionals:

Each vial of Voraxaze must be reconstituted with 1 mL of sterile 0.9% sodium chloride solution. Reconstitution must be performed immediately prior to use (do not dilute further). It must be administered intravenously by means of a 5-minute intravenous bolus injection.
After reconstitution with 1 mL of sterile 0.9% sodium chloride solution, each mL will contain 1,000 units of glucarpidase. A suitable syringe for withdrawing small volumes must be used to extract the solution from the vials. It may not always be possible to withdraw a full 1 mL from the vial, but withdrawal of at least 0.90 mL from the vial will provide an adequate amount of glucarpidase for dosing.
Any unused medicinal product and waste materials derived from such medicinal product must be disposed of in accordance with local regulations.
ANNEX IV
CONCLUSIONS ON THE GRANTING OF A MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES PRESENTED BY THE
EUROPEAN MEDICINES AGENCY
Conclusions presented by the European Medicines Agency on:

• Granting of a marketing authorisation under exceptional circumstances
  Following assessment of the marketing authorisation application, the Committee for Medicinal Products for Human Use (CHMP) considers that the benefit-risk balance is favourable to support the recommendation for granting a marketing authorisation under exceptional circumstances, as further described in the European Public Assessment Report (EPAR).