VORAXAZE 1000 UNITS POWDER FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Voraxaze 1,000 units powder for solution for injection

Glucarpidase

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of the leaflet includes information on how to report side effects.

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack

1. What is Voraxaze and what is it used for
2. What you need to know before you are given Voraxaze
3. How to take Voraxaze
4. Possible side effects
5. Storage of Voraxaze
6. Contents of the pack and other information

1. What is Voraxaze and what is it used for

The active substance in this medicine is glucarpidase, an enzyme that breaks down the medicine methotrexate to treat cancer.

Voraxaze is indicated in adults and children over 28 days, if they are receiving methotrexate for cancer treatment, but their body is not able to eliminate methotrexate quickly enough and they are at risk of severe side effects. The medicine breaks down methotrexate in the blood, reducing methotrexate levels and thus helping to control side effects, preventing them from worsening. The medicine acts very quickly and can reduce the amount of methotrexate in the blood by more than 90% in 15 minutes. The medicine does not penetrate cells, so it does not prevent methotrexate that has already entered cancer cells from acting to treat cancer.

2. What you need to know before you are given Voraxaze

Do not take Voraxaze

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

Warnings and precautions

Talk to your doctor before you are given Voraxaze.

You will receive this medicine as soon as your doctor decides that you need it to prevent severe side effects of methotrexate.

This medicine cannot on its own prevent or stop all side effects of high doses of methotrexate, and you will also be given other treatments and supportive care as needed.

It is important that your doctor knows how much methotrexate is in your blood and how well your kidneys are working.

You will have tests to check this before and after treatment with this medicine.

Children and adolescents

This medicine can be given to children over 28 days. The safety and efficacy of this medicine in children under 28 days have not been established.

Other medicines and Voraxaze

This medicine may affect the amount of folinic acid in your body, another product that your doctor may give you to reduce the toxicity of methotrexate. As a precaution, your doctor will adjust the schedule of your folinic acid and your doses of Voraxaze to ensure that at least 2 hours pass between the administration of the two medicines. Your doctor will restart the administration of folinic acid no less than 2 hours after the administration of glucarpidase.

No other interactions between this and other medicines have been reported during clinical studies.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor.

Since this medicine is only used in people who have already received methotrexate, which is known to cause harmful effects on the developing baby, no studies have been done to determine if this medicine alone can cause harmful effects on a developing fetus during pregnancy or if it is excreted in breast milk.

Driving and using machines

The influence of this medicine on the ability to drive and use machines is negligible.

3. How to take Voraxaze

This medicine is given by injection into a vein over a 5-minute period. Your doctor will decide the right dose for you, based on your weight. The recommended dose is 50 units per kilogram of body weight.

Because the medicine is given under medical supervision, it is unlikely that you will be given too much. If you think you have been given too much, talk to your doctor or nurse.

You will be monitored to detect 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 gets them.

Tell your doctor or medical staff immediately if you experience any of the following:

• swelling of the throat, chest tightness, difficulty breathing
• swelling of the hands, feet, face, lips or mouth
• rash, with or without redness or swelling of the face
• shaking or chills without fever

If you experience any of the above symptoms, you may be having a severe allergic reaction and may need immediate medical attention. These side effects (allergic reactions) are very rare, and if they occur, they usually occur on the day of treatment.

You should tell your doctor or medical staff as soon as possible if you experience any of the following side effects, which are also rare, but have been reported during treatment with this medicine:

• fever
• headache
• tingling or prickling sensation on the skin ("pins and needles" sensation)
• burning sensation on the skin

If you experience any other side effect not mentioned in this leaflet, tell your doctor or medical staff.

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 is the last day of the month shown.

This medicine will be given to you under medical supervision. Store in a refrigerator (between 2°C and 8°C).

Do not freeze.

Expiry date: This medicine will not be used after the expiry date shown on the vial or outer packaging. The pharmacist will check this before dispensing.

6. Contents of the pack and other information

What Voraxaze contains

The active substance is glucarpidase.

The other ingredients are lactose, trometamol, and zinc acetate dihydrate.

Appearance and packaging

Each pack contains a vial with a white or off-white lyophilized powder, which is reconstituted with 1 ml of sterile sodium chloride 0.9% 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 responsible for batch release

Almac Pharma Services Limited

Seagoe Industrial Estate,

Portadown,

Craigavon,

BT63 5UA, UK (Northern Ireland)

Date of last revision of this leaflet

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

----------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Each vial of Voraxaze should be reconstituted in 1 ml of sterile sodium chloride 0.9% solution.

Reconstitution should be performed immediately prior to use (do not dilute further). It should be administered by intravenous injection over a 5-minute period.

After reconstitution in 1 ml of sterile sodium chloride 0.9% solution, it will contain 1,000 units of glucarpidase. A suitable syringe should be used to extract small volumes to extract the solution from the vials. It may not always be possible to extract a full 1 ml from the vial, but extracting at least 0.90 ml from the vial will provide an adequate amount of glucarpidase for administration.

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