Prospect: information for the patient

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

Dexrazoxane

Read the entire prospect carefully before starting to use the medication, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

1.What is Savene and for what it is used

2.What you need to know before starting to use Savene

3.How to use Savene

4.Possible adverse effects

5Storage of Savene

6.Contents of the package and additional information

Savene contains the active ingredient dexrazoxane, which acts as an antidote for cancer medications called anthracyclines.

Most cancer medications are administered intravenously (into a vein). Sometimes an accident occurs and the medication leaks out of the vein into surrounding tissue or escapes from the vein into surrounding tissue. This event is called extravasation. It is a serious complication because it can cause severe damage to the tissue.

Savene is used to treat anthracycline extravasation in adults.

It may reduce the amount of tissue damage caused by anthracycline extravasation.

No use Savene:

-If you are allergic to dexrazoxane or any of the other components of this medication (listed in section 6).

-If you are planning to become pregnant and do not use adequate birth control measures

-If you are breastfeeding your baby

-If you are being administered the yellow fever vaccine.

Warnings and precautions

Consult your doctor or nurse before starting to use Savene:

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

Children and adolescents

Savene should not be administered to children under 18 years old.

Use of Savene with other medications

Inform your doctor or nurse if you are using, have used recently, or may need to use any other medication.

Particularly, inform your doctor or nurse if you are using or may use any of the following medications:

• Vaccines: do not use Savene if you are to be administered the yellow fever vaccine and it is not recommended to use Savene if you are to be administered a vaccine that contains live virus particles.
• A product called DMSO (a cream for treating some skin diseases)
• Phenytoin (a treatment for seizures) Savene may reduce the effectiveness of this medication).
• Anticoagulants (which thin the blood) (you may need to have more frequent checks).
• Ciclosporin or tacrolimus (both treatments reduce the body's immune system and are used to prevent organ rejection after an organ transplant).
• Myleosuppressive medications (which reduce the production of red, white blood cells, or platelets).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor before using this medication.

Savene should not be administered if you are pregnant.

It is not possible to breastfeed while under treatment with Savene.

If you are sexually active, it is recommended that you use an effective birth control method to prevent pregnancy during treatment and for 6 months after this, both for men and women (see section 2 “Do not use Savene”).

The information on the effect of Savene on fertility is limited. If you have any concerns, speak with your doctor.

Driving and operating machinery

There have been reports of dizziness, fatigue, and sudden fainting in a few patients treated with Savene. It is considered that the treatment has a limited influence on the ability to drive and operate machinery.

Savene contains potassium and sodium

The Savene solvent contains 98 mg of potassium per 500 ml bottle, which can be harmful to people with a low-potassium diet or those with 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 table salt) per 500 ml bottle. This is equivalent to 81% of the recommended daily maximum intake of sodium in an adult's diet.

Savene will be administered under the supervision of an experienced oncologist.

Recommended dose

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

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

Administration frequency

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

Savene will not be reused in the following cycle of anthracycline, unless extravasation occurs again.

If you receive more Savene than you should

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

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

If you have any other questions about the use of this medication, ask your doctor or nurse.

Like all medicines, this medicine can have side effects, although not everyone will experience them.

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

The following serious side effects have been reported in patients during treatment with Savene (frequency unknown):

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

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

The following possible side effects are listed below:

Very common: may affect more than 1 in 10 people

• Nausea
• Reaction at the injection site (pain in the area, redness, swelling, or pain in the skin of the area or hardening of the skin of the area)
• Reduction in the number of white blood cells and platelets
• Infection (after surgery or other infections)

Common: may affect up to 1 in 10 people

• Vomiting
• Diarrhea
• Sensation of fatigue, drowsiness, dizziness, sudden fainting
• Reduction of any of the senses (vision, smell, hearing, touch, taste)
• Fever
• Inflammation of the blood vessel where the treatment is administered (phlebitis)
• Inflammation of the blood vessel that is located just under the skin, which often presents a small blood clot
• Blood clot in a vein, usually in an arm or leg
• Inflammation of the mouth
• Dry mouth
• Hair loss
• Itching (pruritus)
• Weight loss, decreased appetite
• Muscle pain, tremors (uncontrolled muscle movements)
• Vaginal bleeding
• Respiratory difficulties
• Pneumonia (lung infection)
• Swelling of the arms or legs (edema)
• Wound complications
• Alterations in liver function (which may be observed in test results)

Reporting of side effects

If you experience any type of side effect, consult your doctor or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.esBy reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box, the vial of powder label, and the solvent bottle label after “CAD”. The expiration date is the last day of the month indicated.

Store below 25 °C.

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

Composition of Savene

- The active ingredient is dexrazoxane. Each vial contains 500 mg of dexrazoxane as 589 mg of dexrazoxane hydrochloride.

- The other components are: the solvent containing sodium chloride, potassium chloride, hexahydrate of magnesium chloride, sodium acetate trihydrate, sodium gluconate, sodium hydroxide, and water for injection.

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. An emergency kit contains 10 vials of Savene powder and 3 bottles of Savene solvent supplied with 3 bottle hangers.

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

Holder of the marketing authorization and manufacturer

Holder of the marketing authorization

Clinigen Healthcare B.V.

Schiphol Boulevard 359

WTC Schiphol Airport, D Tower 11th floor

1118BJ Schiphol

Netherlands

Responsible for manufacturing

Cenexi-Laboratoires Thissen SA

Rue de la Papyrée 2-4-6

B-1420 Braine-L’Alleud

Belgium

Last review date of this leaflet: 07/2018

Other sources of information

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

This information is intended solely for healthcare professionals.

Guidelines for preparation for use with Savene 20 mg/ml powder and solvent for concentrate for solution for infusion

____________________________________________________________________________

It is essential to read this entire procedure carefully 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 diluted again in the remaining Savene solvent before administration.

1. RECOMMENDATIONS FOR SAFE HANDLING

Savene is an antineoplastic, so the following normal procedures for safe handling and disposal of antineoplastics must be adopted:

• The personnel must receive training to reconstitute the medication.
• Pregnant women who are part of the personnel must be excluded from working with this medication.
• Personnel handling this medication during reconstitution must wear protective clothing, including a mask, glasses, and gloves.
• Accidental contact with the skin or eyes must be treated immediately with abundant water.

1. PREPARATION FOR INTRAVENOUS ADMINISTRATION

3.1Reconstitution of Savene powder to prepare a concentrate

3.1.1Using a syringe with an incorporated needle, extract 25 ml of Savene solvent from the bottle in an aseptic manner.

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

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

3.1.4Leave the vial with the concentrate at room temperature for 5 minutes and then check that the solution is homogeneous and transparent. The concentrate is slightly yellow.

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

3.2Dissolution of the concentrate

3.2.1Up to four vials of Savene concentrate may be required to obtain the required dose for the patient. Extract the corresponding volume, containing 20 mg of dexrazoxane per ml, from the appropriate number of vials of concentrate, based on the required dose for the patient expressed in mg, using a graduated syringe equipped with a needle.

3.2.2Inject the reconstituted volume necessary into the open bottle of Savene solvent (see point 3.1.5). The solution must not be mixed with any other medication.

3.2.3Mix the solution by shaking the infusion bottle carefully.

3.2.4Savene must be administered in an aseptic manner as an infusion of 1–2 hours at room temperature and under normal lighting conditions.

3.2.5As with all parenteral products, Savene concentrate and Savene infusion solution must be visually inspected before use to discard any solutions containing particles or presenting discoloration. Solutions showing precipitation must be discarded.

1. CONSERVATION

4.1 Before reconstitution and dilution:

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

4.2 Once reconstituted and diluted:

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

1. ELIMINATION

All elements used for preparation, administration, or cleaning, including gloves, as well as the excess liquid must be disposed of in accordance with local regulations.