Savene 20 mg/ml powder for concentrate and diluent for solutionfor infusion

Savene is a detoxifying agent for anti-cancer treatment.

Most anti-cancer medicines are administered intravenously. Occasionally an accident occurs and the medicine is infused outside the vein and into the surrounding tissue. This event is called extravasation. It is a serious complication as it can cause severe tissue damage. Savene is used as an antidote to treat extravasations caused by the group of anti-cancer medicines called anthracyclines.

2. BEFORE YOU ARE GIVEN SAVENE

Savene will not be used:

• If you are allergic (hypersensitive) to dexrazoxane or any of the other ingredients of Savene
• If you are planning to become pregnant and do not use adequate contraceptive measures
• If you are breast-feeding
• If you are given yellow fever vaccine

Special care with Savene should be taken

• Savene should only be given to you if you have had an extravasation in connection with anthracycline-containing chemotherapy.
• During treatment with Savene you will have blood tests taken regularly to check your blood cells.
• If you have liver dysfunction your doctor will monitor your liver function during treatment
• If you have kidney dysfunction your doctor will monitor for signs of changes to your blood cells.
• Men being treated with dexrazoxane are advised not to father a child during and up to three months after treatment.
• Women of childbearing potential must use contraceptive measures during treatment.
• If you receive live attenuated vaccines or phenytoin (anti-epileptic medicines).
• Savene should not be administered to children.

Taking other medicines

Savene should not be mixed with any other medicines during the infusion.
It is not advisable to use any medical treatment without telling your doctor as there may be interactions between Savene and other medicines.

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

Savene should not be administered if you are pregnant. If you are a man, you must take adequate contraceptive precautions during therapy and for at least three months after treatment. You must not breast-feed while you are treated with Savene.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines
No studies on the effects on the ability to drive and use machines have been performed but it is unlikely that Savene will affect this function.

Important information about some of the ingredients of Savene

The Savene diluent contains potassium (98 mg/500 ml) which may be harmful to people on a low potassium diet.
It also contains sodium (1.61 g/500 ml) which may be harmful to people on a low sodium diet.

Usual dose

The dose will depend on your height and weight. Your doctor will calculate your body surface area in square meter (m 2) and will determine the dose you should receive.

The usual adult dose is
Day 1 and Day 2: 1000 mg/m 2
Day 3: 500 mg/m2

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

Before infusion, Savene powder is reconstituted with 25 ml sterile water to give a concentration of 20 mg dexrazoxane per ml sterile water.
After reconstitution the solution should be further diluted in the bag with the Savene diluent.

Frequency of administration

You will receive your infusion once daily for 3 consecutive days. The first infusion will be given as soon as possible, and within the first six hours, after extravasation with an anthracycline medicine.

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

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

Side effects described as very common were experienced by more than 1 in 10 patients. Side effects described as common were experienced by up to 1 in 10 patients.

The very common (more than 1 in 10 patients) side effects are:
Nausea. Pain in the blood vessel where the treatment is given. Very common side effects are furthermore a temporary lowering of the white blood cells, neutrophils and the platelets, side effects which also are caused by the chemotherapy you receive for your disease. Control blood tests will be performed regularly.

The common (up to 1 in 10 patients) side-effects are:
A general feeling of being unwell including feeling tired, sleepy or dizzy. Furthermore there can be inflammation of the blood vessel where the treatment is given (phlebitis), diarrhoea, dry mouth, hair loss. At the site of injection you may get a reaction, where the skin may be red, swollen or hurt when touched.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

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

Side effects described as very common were experienced by more than 1 in 10 patients. Side effects described as common were experienced by up to 1 in 10 patients.

The very common (more than 1 in 10 patients) side effects are:
Nausea. Pain in the blood vessel where the treatment is given. Very common side effects are furthermore a temporary lowering of the white blood cells, neutrophils and the platelets, side effects which also are caused by the chemotherapy you receive for your disease. Control blood tests will be performed regularly.

The common (up to 1 in 10 patients) side-effects are:
A general feeling of being unwell including feeling tired, sleepy or dizzy. Furthermore there can be inflammation of the blood vessel where the treatment is given (phlebitis), diarrhoea, dry mouth, hair loss. At the site of injection you may get a reaction, where the skin may be red, swollen or hurt when touched.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not use Savene after the expiry date stated on the label.

Savene should be stored below 25oC. Keep Savene in the outer carton in order to protect from light.

Chemical and physical in-use stability has been demonstrated for 4 hours when stored at 2 to 8 oC after reconstitution and subsequent dilution in the diluent.

From a microbiological point of view the product should be used immediately.
If not used immediately, in-use storage times and conditions prior to use are at the responsibility of the user and would normally not be longer than 4 hours at 2 to 8°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Do not use Savene if you notice that the vial is damaged or show signs of tampering.

What Savene contains

The active substance is dexrazoxane. Each vial contains 500 mg dexrazoxane as 589 mg dexrazoxane hydrochloride.

The other ingredients are hydrochloric acid.

The diluent 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

Savene consists of Savene powder and Savene diluent. Savene powder is presented as a single glass vial containing a white to off-white powder called dexrazoxane (the active substance). Savene is also supplied with an infusion bag containing the Savene diluent.

The concentration of the active ingredient following reconstitution with sterile water is 20 mg dexrazoxane per ml. The reconstituted solution is slightly yellow.

Savene is supplied in a box containing 10 vials of Savene powder and 3 infusion bags of Savene diluent.

Marketing Authorisation Holder and Manufacturer:
SpePharm Holding B.V.
Kingsfordweg 151
NL ? 1043 GR Amsterdam
Netherlands
Tel: +31 (0)88 0074 501
Fax: +31 (0)20 4919 090

For any information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam TélTel 31 088 0074 501 LuxembourgLuxemburg SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam TélTel 31 088 0074 501

SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Te. 31 088 0074 501 Magyarország Medis d.o.o. Brnciceva 1 SI-1001 Ljubljana Tel. 386 1 589 69 00

eská republika SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501 Malta SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

Danmark SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tlf 31 088 0074 501 Nederland SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

Deutschland SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501 Norge SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam n Tlf 31 088 0074 501

Eesti SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501 Österreich SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

a VIPharma International A.E. 43 GR 151 26 30 210-6194170 Polska SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel. 31 088 0074 501

España Ferrer Farma, S.A. Gran Vía Carlos III, 94 E - 08028 Barcelona Tel 34 93 600 37 00 Portugal Ferrer Azevedos, S.A. Edificio Azevedos, Estrada Nacional 117-2 P-2614-503 Amadora Tel 351 21 4725900

France SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam România SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam

Tél 31 088 0074 501 Tel 31 088 0074 501

Ireland SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501 Slovenija Medis d.o.o. Brnciceva 1 SI-1001 Ljubljana Tel 386 1 589 69 00

Ísland SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Sími 31 088 0074 501 Slovenská republika SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

Italia SpePharm Italia s.r.l. Via F. Baracca, 11 IT- 21047 Saronno VA Tel 39 029 670 4068 SuomiFinland SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam PuhTel 31 088 0074 501

SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam 31 088 0074 501 Sverige SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

Latvija SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501 United Kingdom SpePharm Holding B.V. Kingsfordweg 151 NL 1043 GR Amsterdam Tel 31 088 0074 501

Lietuva
SpePharm Holding B.V.
Kingsfordweg 151
NL ? 1043 GR Amsterdam
Tel: + 31 (0)88 0074 501

This leaflet was last approved in

The following information is intended for medical or healthcare professionals only.

Preparation guide for use with Savene powder for concentrate and diluent for solution for infusion

It is important that you read the entire content of this procedure prior to the preparation of Savene.

1. FORMULATION

Savene is supplied as:

1. Savene powder

2. Savene diluent

Savene powder must be reconstituted in 25 ml sterile water and diluted in 500 ml diluent prior to administration.

2. RECOMMENDATION FOR THE SAFE HANDLING

Savene is an anti-cancer agent and the normal procedures for proper handling and disposal of anticancer medicines should be adopted, namely:

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

3. PREPARATION FOR THE INTRAVENOUS ADMINISTRATION

3.1 Reconstitution of Savene powder

3.1.1 Using a syringe fitted with a needle, aseptically withdraw 25 ml of sterile water. 3.1.2 Inject the entire contents of the syringe into the vial containing the Savene powder. 3.1.3 Remove the syringe and needle and mix manually by repeated inversions until the powder is fully dissolved. Do not shake.
3.1.4 Allow the vial with the reconstituted solution to stand for 5 minutes at room temperature and check if the solution is homogenous and clear. The reconstituted solution is slightly yellow. The reconstituted solution contains 20 mg dexrazoxane per ml and should be used immediately after preparation. It contains no antibacterial preservative.

3.2 Dilution of the infusion concentrate

3.2.1 More than one vial containing reconstituted solution may be necessary to obtain the required dose for the patient. Based on the required dose for the patient expressed in mg, aseptically withdraw the corresponding reconstituted volume containing 20 mg dexrazoxane per ml from the appropriate number of vials containing reconstituted solution. Use a graduated syringe filled with a needle.
3.2.2 Inject the required reconstituted volume into the infusion bag with 500 ml diluent. The solution must not be mixed with any other medicines.
3.2.3 Mix the infusion bag manually using a rocking motion
3.2.4 Savene should be aseptically administered as a 1-2 hours infusion under room temperature and normal light conditions.
3.2.5 As with all parenteral products, Savene reconstituted solution and infusion solution should be inspected visually for particulate matter and discoloration prior to administration. Solutions containing a precipitate should be discarded.

4. DISPOSAL

All items for preparation, administration or cleaning, including gloves, as well as liquid waste should be disposed of in accordance with local requirements.