Savene

Package leaflet: Information for the patient

Savene 20 mg/ml powder and solvent for concentrate for solution for infusion

Dexrazoxane
Please read this leaflet carefully before using this medicine because it contains important information for you.

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

Contents of this leaflet:

1. What Savene is and what it is used for
2. What you need to know before using Savene
3. How to use Savene
4. Possible side effects
5. How to store Savene
6. Contents of the pack and other information

1. What Savene is and what it is used for

Savene contains the active substance dexrazoxane, which acts as an antidote to a group of anticancer medicines called anthracyclines.
Most anticancer medicines are administered intravenously (into a vein).
Sometimes, accidentally, the medicine may be injected outside the vein or may leak out of the vein and come into contact with the surrounding tissue. This event is known as extravasation. It is a serious complication because it can cause severe tissue damage.
Savene is used for the treatment of anthracycline extravasations in adults. It may reduce the amount of tissue damage caused by anthracycline extravasation.

2. What you need to know before using Savene

Do not use Savene:

• if you are allergic to dexrazoxane or to any of the other ingredients of this medicine (listed in section 6)
• if you are planning a pregnancy and are not using effective contraceptive measures
• if you are breastfeeding
• if you are receiving the yellow fever vaccine

Warnings and precautions
Talk to your doctor or nurse before using Savene:

• Savene must only be used in cases of extravasation associated with anthracycline-based chemotherapy.
• During treatment with Savene, the area where the extravasation occurred must be regularly examined, and you must undergo regular blood tests to monitor blood cells.
• If you have liver problems, your doctor will monitor liver function during treatment.
• If you have kidney problems, your doctor must perform checks to detect any signs of blood cell abnormalities.

Children and adolescents
Savene must not be administered to children under 18 years of age.
Other medicines and Savene
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor or nurse if you are taking or might take any of the following medicines:

• vaccines: you must not use Savene if receiving the yellow fever vaccine, and the use of Savene should be avoided if receiving a vaccine containing live virus particles;
• a product called DMSO (a cream used to treat certain skin diseases);
• phenytoin (a treatment for seizures), as Savene may reduce the effectiveness of this medicine;
• anticoagulants (blood thinners), more frequent blood monitoring may be required;
• cyclosporine or tacrolimus (both used for immunosuppression and to prevent organ rejection after transplantation);
• myelosuppressive medicines (which reduce the production of white and red blood cells and platelets).

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor before taking this medicine.
Savene must not be administered during pregnancy.
You must not breastfeed during treatment with Savene.
If you are sexually active, it is recommended to use effective contraceptive methods to prevent pregnancy during treatment and for six months after treatment, whether you are a man or a woman (see section 2 "Do not use Savene").
Information on the effect of Savene on fertility is limited; if you have any concerns, discuss them with your doctor.
Driving and using machines
Dizziness, fatigue and sudden fainting have been observed in a small number of patients treated with Savene. The treatment is considered to have a limited influence on the ability to drive vehicles and use machines.
Savene contains potassium and sodium
Savene solvent contains 98 mg of potassium per 500 ml vial, which may be harmful for people on a low-potassium diet or with kidney problems. If you are at risk of high potassium levels in the blood, your doctor will monitor these levels.
Savene solvent also contains 1.61 g of sodium (the main component of common table salt) per 500 ml vial. This amount corresponds to 81% of the maximum daily recommended sodium intake in an adult's diet.

3. How to use Savene

Savene will be administered under the supervision of a doctor experienced in the use of anticancer treatments.
Recommended dose
The dose depends on the patient's height, weight, and renal function. Your doctor must calculate your body surface area in square metres (m²) to determine the dose you should receive. The recommended dose for adult patients (with normal renal function) is:
Day 1: 1000 mg/m²
Day 2: 1000 mg/m²
Day 3: 500 mg/m²
Your doctor may reduce your dose if you have renal problems.
Savene is administered by intravenous infusion. The infusion lasts 1 or 2 hours.
Frequency of administration
The infusion should be given once daily for 3 consecutive days. The first infusion must be administered as soon as possible and within the first six hours after extravasation of an anthracycline.
The Savene infusion will be given at the same time each day during treatment.
Savene will not be used again during the next cycle of anthracycline, except in the event of a new extravasation.
If you receive more Savene than you should
If you are given more Savene than prescribed, you will be closely and carefully monitored for blood cells, possible gastrointestinal symptoms, skin reactions, and hair loss.
If Savene comes into contact with the skin, the affected area must be immediately and thoroughly rinsed with water.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Some side effects may be serious and require immediate medical attention.
In patients treated with Savene, the following serious side effects have been observed (frequency not known):

• Allergic reactions including itching, rash, swelling of face/throat, wheezing, shortness of breath or difficulty breathing, changes in level of consciousness, hypotension, sudden fainting.

If you experience any of the symptoms listed above, seek immediate medical advice.
Other possible side effects are the following:
Very common: may affect more than 1 in 10 people

• Nausea
• Injection site reactions (pain, redness, swelling or tenderness at the injection site, hardening at the injection site)
• Decrease in white blood cells and platelets
• Infection (following surgery or other infections)

Common: may affect up to 1 in 10 people

• Vomiting
• Diarrhoea
• Feeling tired, drowsiness, dizziness, sudden fainting
• Reduction in any of the senses (vision, smell, hearing, touch, taste)
• Fever
• Inflammation of the blood vessel where treatment is administered (phlebitis)
• Inflammation of a vein just under the skin, often with a small blood clot
• Blood clot in a vein, usually in an arm or leg
• Inflammation of the mouth
• Dry mouth
• Hair loss
• Itching
• Weight loss, loss of appetite
• Muscle pain, tremor (involuntary muscle movements)
• Vaginal bleeding
• Difficulty breathing
• Pneumonia (lung infection)
• Swelling of arms or legs (oedema)
• Wound complications
• Changes in liver function (seen in test results)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Savene

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, on the label of the vial containing the powder, and on the label of the solvent vial following "EXP". The expiry date refers to the last day of that month.
Store below 25 °C.
Keep the vials containing the powder and the vials containing the solvent in the outer packaging to protect the medicine from light.

6. Package contents and other information

What Savene contains

• The active substance is dexrazoxane. Each vial contains 500 mg of dexrazoxane in the form of 589 mg of dexrazoxane hydrochloride.
• The other components are: the solvent containing Sodium chloride, Potassium chloride, Magnesium chloride hexahydrate, Sodium acetate trihydrate, Sodium gluconate, Sodium hydroxide, and Water for injections.

Description of the appearance of Savene and contents of the emergency kit
The Savene kit consists of Savene, powder for concentrate (white to off-white powder) and Savene solvent. One emergency kit contains 10 vials of Savene powder and 3 vials of Savene solvent, together 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
CNX Therapeutics Ireland Limited
5th Floor Rear, Connaught House
1 Burlington Road
Dublin 4, Dublin
Ireland

Manufacturer
Cenexi-Laboratoires Thissen SA
Rue de la Papyrée 2-4-6
B-1420 Braine-L’Alleud
Belgium

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

The following information is intended for healthcare professionals only.

Instructions for the preparation of Savene 20 mg/ml powder and solvent for concentrate for solution for infusion
Before starting the preparation of Savene, it is important to read the entire content of this procedure.

1. COMPOSITION

Savene is supplied as:

1. Savene Powder for concentrate
2. Solvent for Savene

Prior to administration, the Savene powder must be reconstituted in 25 ml of Savene solvent to obtain a concentrate, which must then be further diluted with the remaining Savene solvent.

2. RECOMMENDATIONS FOR SAFE HANDLING

Savene is an antineoplastic agent. Therefore, standard procedures for the safe handling and disposal of antineoplastic medicinal products must be followed, in particular:

• Personnel must be adequately trained to perform the reconstitution of the medicinal product
• Pregnant personnel must not handle this medicinal product
• Personnel handling this medicinal product during reconstitution must wear protective clothing, including mask, protective goggles, and gloves
• In case of accidental contact with the skin or eyes, immediate action must be taken; thoroughly wash with copious amounts of water

3. PREPARATION FOR INTRAVENOUS USE

3.1 Reconstitution of Savene powder for concentrate preparation
3.1.1 Using a syringe with needle inserted, 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 with needle inserted and mix manually by inverting several times until the powder is completely dissolved. Do not shake.
3.1.4 Allow the vial containing the concentrate to stand for 5 minutes at room temperature and check that the solution is homogeneous and clear. The concentrated solution is slightly yellow.
The concentrated solution contains 20 mg of dexrazoxane/ml and must be used immediately for further dilution. It contains no antibacterial preservatives.
3.1.5 Keep and store the opened solvent vial under aseptic conditions, as it is required for dilution of the concentrate.

3.2 Dilution of the concentrate
3.2.1 To obtain the required dose for the patient, up to four vials of Savene concentrate may be needed. Depending on the required patient dose expressed in mg, aseptically withdraw the corresponding volume containing 20 mg of dexrazoxane/ml from the required number of vials containing the concentrate. Use a graduated syringe with needle inserted.
3.2.2 Inject the required reconstituted volume into the opened Savene solvent vial (see section 3.1.5).
Do not mix the solution with other medicinal products.
3.2.3 Mix the solution by gently agitating the infusion vial.
3.2.4 Savene must be administered under aseptic conditions by 1- or 2-hour infusion, at room temperature and under normal light conditions.
3.2.5 As with all parenteral products, before administration, the Savene concentrated solution and the infusion solution should be visually inspected for presence of particulate matter and discoloration. Solutions containing a precipitate must be discarded.

4. STORAGE

4.1 Before reconstitution and dilution

• Store below 25 °C.
• Keep vials and bottles in the outer packaging to protect the medicinal product from light.

4.2 After reconstitution and dilution

• Chemical and physical in-use stability has been demonstrated for 4 hours if the preparation is stored at a temperature between 2 and 8 °C.
• To avoid possible microbial contamination, the product should be used immediately.
• If not used immediately, the product must be stored in a refrigerator at a temperature between 2 and 8 °C and used within 4 hours.

5. DISPOSAL OF THE PRODUCT

All components required for preparation, administration or cleaning, including gloves,
and liquid residues, must be disposed of in accordance with local legal requirements.