SAVENE 20 mg/ml POWDER FOR CONCENTRATE AND SOLVENT FOR PERFUSION SOLUTION

2. What you need to know before you use Savene

Do not use Savene:

• If you are allergic to dexrazoxane or any of the other ingredients of this medicine (listed in section 6).
• If you are planning to become pregnant and are not using adequate contraceptive measures
• If you are breast-feeding
• If you are being given the yellow fever vaccine.

Warnings and precautions

Talk to your doctor or nurse before you start using Savene:

• Savene should only be given to you if you have had an extravasation when receiving chemotherapy with anthracyclines.
• During treatment with Savene, the area where the extravasation occurred will be regularly examined and you will have regular blood tests to check your blood cells.
• If you have liver problems, your doctor will monitor your liver function during treatment.
• If you have kidney problems, your doctor will monitor any signs of changes in your blood cells.

Children and adolescents

Savene must not be given to children under 18 years of age.

Using Savene with other medicines

Tell your doctor or nurse if you are using, have recently used or might use any other medicines.

In particular, tell your doctor or nurse if you are using or might use any of the following medicines:

• Vaccines: you must not use Savene if you are going to be given the yellow fever vaccine and it is not recommended to use Savene if you are going to be given a vaccine that contains live virus particles.
• A product called DMSO (which is a cream used to treat certain skin conditions)
• Phenytoin (a treatment for fits) Savene may reduce the effectiveness of this medicine.
• Anticoagulants (which thin the blood) (you may need to have more frequent checks).
• Ciclosporin or tacrolimus (both of which reduce the body's immune system and are used to prevent organ rejection after an organ transplant).
• Medicines that reduce the production of red, white or platelet blood cells.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Savene must not be given if you are pregnant.

You must not breast-feed if you are being treated with Savene.

If you are sexually active, you are advised to use an effective method of contraception to prevent pregnancy during treatment and for 6 months after treatment, both if you are male or female (see section 2 “Do not use Savene”).

Information on the effect of Savene on fertility is limited. If you have any concerns about this, talk to your doctor.

Driving and using machines

Dizziness, fatigue and sudden fainting have been reported in a few patients treated with Savene. The treatment is considered to have a minor influence on the ability to drive and use machines.

Savene contains potassium and sodium

The Savene solvent contains 98 mg of potassium per 500 ml vial which may be harmful to people on a low potassium diet or who have kidney problems. If you are at risk of having high levels of potassium in your blood, your doctor will monitor this.

The Savene solvent also contains 1.61 g of sodium (the main component of cooking/table salt) per 500 ml vial. This is equivalent to 81% of the maximum recommended daily intake of sodium in the diet of an adult.

3. How to use Savene

Savene will be given to you under the control of a doctor with experience in the use of cancer treatments.

Recommended dose

The dose will depend on your height, weight and kidney function. Your doctor will calculate your body surface area in square metres (m2) to determine the dose you should receive. The recommended dose in adults (with normal kidney function) is:

Day 1: 1,000 mg/m2

Day 2: 1,000 mg/m2

Day 3: 500 mg/m2

Your doctor may reduce your dose if you have kidney problems.

Savene will be given to you by infusion into one of your veins. The infusion will last 1-2 hours.

Frequency of administration

You will receive your infusion once a day for 3 consecutive days. The first infusion will be given as soon as possible and within the first 6 hours after anthracycline extravasation. The Savene infusion will be given at the same time each day of treatment.

Savene will not be used again in the next cycle of anthracycline treatment unless another extravasation occurs.

If you receive more Savene than you should

If you receive more Savene than you should, you will be closely monitored, with particular attention to your blood cells, possible gastrointestinal signs, skin reactions and hair loss.

If Savene comes into contact with the skin, the affected area should be rinsed immediately with plenty of water.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some side effects can be serious and need immediate medical attention.

The following serious side effects have been reported in patients during treatment with Savene (frequency not known):

• Allergic reactions, whose symptoms could be itching (pruritus), rash, swelling of the face/throat, wheezing, shortness of breath or difficulty breathing, changes in levels of consciousness, low blood pressure, sudden fainting

If you experience any of the above symptoms, seek medical attention immediately.

The following are other possible side effects:

Very common: may affect more than 1 in 10 people

• Nausea
• Reactions at the injection site (pain at the site, redness, swelling or pain in the skin at the site or hardening of the skin at the site)
• Reduced number of white blood cells and platelets
• Infection (after an operation or other infections)

Common: may affect up to 1 in 10 people

• Vomiting
• Diarrhoea
• Feeling tired, sleepy, dizzy, sudden fainting
• Reduced sense of touch, taste, smell, hearing or sight
• Fever
• Inflammation of the blood vessel where the treatment is given (phlebitis)
• Inflammation of the blood vessel just under the skin, which often has a small blood clot
• Blood clot in a vein, usually in an arm or leg
• Mouth inflammation
• Dry mouth
• Hair loss
• Itching (pruritus)
• Weight loss, decreased appetite
• Muscle pain, tremors (uncontrolled muscle movements)
• Vaginal bleeding
• Breathing difficulties
• Pneumonia (lung infection)
• Swelling of the arms or legs (oedema)
• Wound complications
• Changes in liver function (which may be seen in blood test results)

Reporting of side effects

If you experience any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines Monitoring System for Human Use: www.notificaRAM.es By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Savene

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, the label on the powder vial and the label on the solvent vial after “EXP”. The expiry date refers to the last day of the month shown.

Store below 25°C.

Store the powder vials and solvent vials in the outer packaging to protect them from light.

6. Contents of the pack and further information

What Savene contains

• The active substance is dexrazoxane. Each vial contains 500 mg of dexrazoxane as 589 mg of dexrazoxane hydrochloride.
• The other ingredients are: the solvent which contains sodium chloride, potassium chloride, magnesium chloride hexahydrate, sodium acetate trihydrate, sodium gluconate, sodium hydroxide and water for injections.

What Savene looks like and contents of the pack

The Savene pack consists of Savene powder for concentrate (white to off-white powder) and Savene solvent. An emergency pack contains 10 vials of Savene powder and 3 vials of Savene solvent supplied with 3 vial hangers.

The concentration of dexrazoxane after reconstitution with 25 ml of Savene solvent is 20 mg/ml. The concentrate is slightly yellow.

Marketing authorisation holder and manufacturer

Marketing authorisation holder

Clinigen Healthcare B.V.

Schiphol Boulevard 359

WTC Schiphol Airport, D Tower 11th floor

1118BJ Schiphol

Netherlands

Manufacturer

Cenexi-Laboratoires Thissen SA

Rue de la Papyrée 2-4-6

B-1420 Braine-L’Alleud

Belgium

Date of last revision of this leaflet: 07/2018

Other sources of information

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

This information is intended only for healthcare professionals.

Preparation guide for use with Savene 20 mg/ml powder and solvent for concentrate for solution for infusion

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It is important that you read carefully the entire contents of this procedure before preparing Savene.

1. FORMULATION

Savene is supplied as follows:

1. Savene powder for concentrate
2. Savene solvent

Savene powder must be reconstituted in 25 ml of Savene solvent to obtain a concentrate that must be further diluted in the remaining Savene solvent before administration.

1. RECOMMENDATION FOR SAFE HANDLING

Savene is an anti-cancer medicine, so the following normal procedures for handling and disposal of anti-cancer medicines should be followed:

• Staff should be trained to reconstitute the medicine.
• Pregnant staff members should be excluded from working with this medicine.
• Staff handling this medicine during reconstitution should wear protective clothing, including mask, glasses and gloves.
• Accidental contact with the skin or eyes should be treated immediately with large amounts of water.

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

3.1Reconstitution of Savene powder to prepare a concentrate

3.1.1 Using a syringe with a built-in needle, aseptically withdraw 25 ml from the Savene solvent vial.

3.1.2 Inject the entire contents of the syringe into the vial containing Savene powder.

3.1.3 Remove the syringe and needle and manually mix by repeatedly inverting until the powder is completely dissolved. Do not shake.

3.1.4 Allow the vial with the concentrate to stand for 5 minutes at room temperature and then check that the solution is homogeneous and clear. The concentrate is slightly yellow.

The concentrate contains 20 mg of dexrazoxane per ml and should be used immediately to further dilute. It does not contain antibacterial preservatives.

1. Maintain and store the opened solvent vial in aseptic conditions, as it is needed to further dilute the concentrate.

3.2Dilution of the concentrate

3.2.1 Up to four vials of Savene concentrate may be needed to obtain the required dose for the patient. Aseptically withdraw the appropriate volume, which contains 20 mg of dexrazoxane per ml, from the appropriate number of vials of concentrate, based on the dose required for the patient expressed in mg. Use a graduated syringe equipped with a needle.

3.2.2 Inject the reconstituted volume back into the opened Savene solvent vial (see point 3.1.5). The solution must not be mixed with any other medicine.

3.2.3 Mix the solution by carefully shaking the infusion vial.

3.2.4 Savene should be administered aseptically as an infusion over 1-2 hours at room temperature and under normal light conditions.

3.2.5 As with all parenteral products, Savene concentrate and the Savene infusion solution should be inspected visually for particulate matter or discolouration prior to administration. Solutions in which precipitation is observed should be discarded.

1. STORAGE

4.1 Before reconstitution and dilution:

• Store below 25°C.
• Store the powder vials and solvent vials in the outer packaging to protect them from light.

4.2 After reconstitution and dilution:

• Chemical and physical stability has been demonstrated for 4 hours when stored between 2 and 8°C after reconstitution and further dilution in the solvent.
• To avoid possible contamination of the medicine by microbes, the product should be used immediately.
• If the medicine is not used immediately, it should normally be stored at a temperature of 2 to 8°C (in the refrigerator) and for no more than 4 hours.

1. DISPOSAL

All items used for preparation, administration or cleaning, including gloves, as well as any leftover liquid, should be disposed of in accordance with local regulations.