Savene

Основна информация

  • Търговско наименование:
  • Savene
  • Използвай за:
  • Хората
  • Вид на лекарството:
  • алопатични наркотици

Документи

Локализация

  • Предлага се в:
  • Savene
    Европейски съюз
  • Език:
  • английски

Терапевтична информация

  • Терапевтична група:
  • ALL OTHER THERAPEUTIC PRODUCTS
  • Терапевтична област:
  • Extravasation of Diagnostic and Therapeutic Materials
  • Терапевтични показания:
  • Savene is indicated for the treatment of anthracycline extravasation.
  • Каталог на резюме:
  • Revision: 14

Състояние

  • Източник:
  • EMA - European Medicines Agency
  • Статус Оторизация:
  • Authorised
  • Номер на разрешението:
  • EMEA/H/C/000682
  • Дата Оторизация:
  • 26-07-2006
  • EMEA код:
  • EMEA/H/C/000682
  • Последна актуализация:
  • 27-12-2019

Доклад обществена оценка

7 Westferry Circus

Canary Wharf

London E14 4HB

United Kingdom

Telephone

+44 (0)20 7418 8400

Facsimile

+44 (0)20 7418 8416

E-mail

info@ema.europa.eu

Website

www.ema.europa.eu

An agency of the European Union

© European Medicines Agency, 2011. Reproduction is authorised provided the source is acknowledged.

EMA/664134/2011

EMEA/H/C/000682

EPAR summary for the public

Savene

dexrazoxane

This document is a summary of the European public assessment report (EPAR) for Savene. It explains

how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its

opinion in favour of granting a marketing authorisation and its recommendations on the conditions of

use for Savene.

What is Savene?

Savene is a powder and diluent that are made up into a solution for infusion (drip into a vein). It

contains the active substance dexrazoxane.

What is Savene used for?

Savene is used to treat extravasation of anthracyclines (a group of anticancer medicines).

Extravasation happens when an anticancer medicine that is normally injected into a vein leaks or is

accidentally injected in the tissue surrounding the vein, where it can cause serious damage.

Because the number of patients who have extravasation of anthracyclines is low, the condition is

considered ‘rare’, and Savene was designated an ‘orphan medicine’ (a medicine used in rare diseases)

on 19 September 2001.

The medicine can only be obtained with a prescription.

How is Savene used?

Savene must be used under the supervision of a doctor who has experience in the use of anticancer

medicines.

The first infusion of Savene is given as soon as possible after the accident, and no later than six hours

after it happened. Two further infusions are then given, one on day 2 and another on day 3, at the

same time as the first infusion. The infusion should last between one and two hours, and be given at a

site other than where the extravasation happened.

How does Savene work?

The active substance in Savene, dexrazoxane, is an antidote to anthracyclines. The way it works is not

entirely clear, but may be linked to the way the medicine attaches to iron in the body to form a

‘chelate’ and to its effect on some enzymes, such as topoisomerase II. Together, these effects can

reduce the amount of tissue damage caused by anthracycline extravasation.

Dexrazoxane has been in use since the 1990s as a medicine to help prevent the cardiomyopathy (harm

to the heart muscle) associated with the use of anthracyclines.

How has Savene been studied?

Savene has been tested in two main studies involving a total of 80 patients who had extravasation of

anthracyclines such as epirubicin or doxorubicin. Savene was not compared with any other medicines

in these studies. The studies looked at how many patients needed surgery to correct the damage due

to the extravasation.

What benefit has Savene shown during the studies?

Only one patient among the 54 in whom the effectiveness of Savene could be measured had tissue

damage requiring surgery.

What is the risk associated with Savene?

The most common side effects with Savene (seen in more than 1 patient in 10) are nausea (feeling

sick), and pain and infection at the site of the injection. Patients can also develop low blood levels of

white blood cells and platelets. Although this may be caused by their anti-cancer treatment, it can also

be caused by Savene, because it is a cytotoxic (a medicine that destroys cells that are multiplying)

that can affect the bone marrow. Patients will be monitored for these side effects before, during and

after treatment. For the full list of all side effects reported with Savene, see the package leaflet.

Savene should not be used in people who may be hypersensitive (allergic) to dexrazoxane or any of

the other ingredients. It must not be used in women who could become pregnant or who are

breastfeeding, or in patients receiving vaccination against yellow fever.

Why has Savene been approved?

Anthracycline extravasation is a condition that can currently be managed using various methods, but

for which there is no standard authorised treatment. The CHMP concluded that Savene had shown its

ability to treat anthracycline extravasation, allowing patients to continue their anticancer treatment.

The Committee decided that Savene’s benefits are greater than its risks and recommended that it be

given marketing authorisation.

Other information about Savene:

The European Commission granted a marketing authorisation valid throughout the European Union for

Savene on 28 July 2006.

The full EPAR for Savene can be found here

. For more information about treatment with Savene, read

the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

Savene

EMA/664134/2011

Page 2/3

Savene

EMA/664134/2011

Page 3/3

The summary of the opinion of the Committee for Orphan Medicinal Products for Savene is available

here

This summary was last updated in 08-2011.

Листовка за пациента: състав, показания, Нежелани лекарствени реакции, дозиране, взаимодействия, бременност, кърмене

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

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

Dexrazoxane

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 or nurse.

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects

not listed in this leaflet. See Section 4.

What is in this leaflet

What Savene is and what it is used for

What you need to know before you use Savene

How to use Savene

Possible side effects

How to store Savene

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 anti-cancer medicines

called anthracyclines.

Most anti-cancer medicines are administered intravenously (into a vein). Occasionally an accident

occurs and the medicine is infused outside the vein and into the surrounding tissue or leaks from the

vein into the surrounding tissue. This event is called extravasation. It is a serious complication as it

can cause severe tissue damage.

Savene is used to treat anthracyline extravasation in adults. It can reduce the amount of tissue damage

caused by anthracycline extravasation.

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 do not use adequate contraceptive measures

If you are breast-feeding

If you are given yellow-fever vaccine

Warnings and precautions

Talk to your doctor or nurse before using Savene:

Savene should only be given to you if you have an extravasation in connection with

anthracycline-containing chemotherapy.

During treatment with Savene the area where the extravasation has occurred will be examined

on a regular basis and you will have blood tests taken regularly 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 for signs of changes to your blood cells.

Children and adolescents

Savene should not be administered to children below the age of 18 years.

Other medicines and Savene

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines.

In particular, tell your doctor or nurse if you are taking or may take any of the following medicines:

Vaccines: you must not use Savene if you are going to receive yellow fever vaccine and it is not

recommended that you use Savene if you are going to receive a vaccine containing live virus

particles.

A product called DMSO (which is a cream to treat some skin diseases).

Phenytoin (a treatment against seizures) (Savene may reduce the effectiveness of this medicine).

Anticoagulants (blood thinners) (your blood may need to be monitored more frequently).

Ciclosporin or tacrolimus (both treatments lower the body's immune system and are used to

prevent organ rejection after an organ transplant).

Myelosuppressive medicines (decrease production of red, white, or coagulating 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 taking this medicine.

Savene should not be administered if you are pregnant.

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

If you are sexually active, you are advised to use effective birth control to prevent pregnancy during

and for six months after treatment, whether you are male or female (see section 2 ‘Do not use

Savene’).

There is limited information about the effect of Savene on fertility – if you have a concern about this

speak to you doctor.

Driving and using machines

Dizziness, tiredness and sudden fainting have been reported in a few patients treated with Savene. The

treatment is considered to have a limited influence on the ability to drive and use machines.

Savene contains potassium and sodium

The Savene solvent contains 98 mg potassium in each 500 ml bottle which may be harmful to people

on a low-potassium diet or who have kidney problems. If you are at risk of high potassium levels in

your blood, your doctor will monitor this.

Savene solvent also contains 1.61 g sodium (main component of cooking/table salt) in each 500 ml

bottle. This is equivalent to 81% of the recommended maximum daily dietary intake of sodium for an

adult.

3.

How to use Savene

Savene will be given to you under the control of a doctor experienced in the use of anti-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 meter (m

) to determine the dose you should receive. The recommended

adult dose (with normal kidney function) is:

Day 1: 1000 mg/m

Day 2: 1000 mg/m

Day 3: 500 mg/m

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

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

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 of an anthracycline medicine. Savene

infusion will be given at the same time every day of your treatment.

Savene will not be used again at the time of your next anthracycline cycle, except if 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 specific attention to

your blood cells, potential gastro-intestinal signs, skin reactions and hair loss.

If Savene comes into contact with the skin, the affected area should immediately be rinsed thoroughly

with 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 effect has been reported in patients during treatment with Savene

(frequency not known):

Allergic reactions, symptoms of which could be itching (pruritis), rash, facial/throat swelling,

wheezing, breathlessness or difficult breathing, changes in levels of consciousness, hypotension,

sudden fainting

If you get any of the above symptoms, seek medical advice immediately.

Other possible side effects are listed below:

Very common: may affect more than 1 in 10 people

Nausea

Reactions at the site of injection (pain at the site, red, swollen or painful skin at the site or

hardening of the skin at the site)

Reduction in the 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, feeling sleepy, feeling dizzy, sudden fainting

Reduction in any of your senses (sight, smell, hearing, touch, taste)

Fever

Inflammation of the blood vessel where the treatment is given (phlebitis)

Inflammation of a blood vessel just under the skin, often with a small blood clot

Blood clot in the vein, usually in an arm or leg

Inflammation in the mouth

Dry mouth

Hair loss

Itching (pruritus)

Weight loss, loss of appetite

Muscle pain, tremor (uncontrolled muscle movement)

Vaginal bleeding

Difficulties in breathing

Pneumonia (lung infection)

Swelling in arms or legs (oedema)

Wound complications

Changes in liver function (these may be seen in test results)

Reporting of side effects

If you get 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 national reporting system listed in

Appendix 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 which is stated on the carton, powder vial label, and

solvent bottle label after ‘EXP’. The expiry date refers to the last day of that month.

Store below 25 °C.

Keep the powder vials and solvent bottles in the outer carton in order to protect from light.

6.

Contents of the pack and other information

What Savene contains

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

dexrazoxane hydrochloride.

The other ingredient(s) 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 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 bottles of Savene solvent

supplied with 3 bottle hangers.

The concentration of dexrazoxane following reconstitution with 25 ml 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

The Netherlands

Manufacturer

Cenexi-Laboratoires Thissen SA

Rue de la Papyrée 2-4-6

B-1420 Braine-L’Alleud

Belgium

This leaflet was last revised in MM/YYYY

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.

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

Savene powder for concentrate

Solvent for Savene

Savene powder must be reconstituted in 25 ml Savene solvent to obtain a concentrate that must be

further diluted in the remaining Savene solvent 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 anti-

cancer 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 to prepare a concentrate

3.1.1

Using a syringe fitted with a needle, withdraw aseptically 25 ml from the Savene solvent bottle.

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 concentrate to stand for 5 minutes at room temperature and check if the

solution is homogenous and clear. The concentrate is slightly yellow.

The concentrate contains 20 mg dexrazoxane per ml and should be used immediately for further

dilution. It contains no antibacterial preservative.

3.1.5

Keep and store the opened solvent bottle under aseptic conditions because it is needed for

dilution of the concentrate.

3.2

Dilution of the concentrate

3.2.1

Up to four vials containing Savene concentrate may be necessary to obtain the required dose for

the patient. Based on the required dose for the patient expressed in mg, withdraw aseptically the

corresponding volume containing 20 mg dexrazoxane per ml from the appropriate number of

vials containing concentrate. Use a graduated syringe filled with a needle.

3.2.2

Inject the required volume back into the opened Savene solvent bottle (see point 3.1.5). The

solution must not be mixed with any other medicines.

3.2.3

Mix the solution by agitating gently the infusion bottle.

3.2.4

Savene should be administered aseptically as a 1-2 hours infusion under room temperature and

normal light conditions.

3.2.5

As with all parenteral products, Savene concentrate and infusion solution should be inspected

visually for particulate matter and discoloration prior to administration. Solutions containing a

precipitate should be discarded.

4.

STORAGE

4.1

Before reconstitution and dilution:

Store below 25

Keep the powder vials and solvent bottles in the outer carton in order to protect from light.

4.2

After reconstitution and dilution:

Chemical and physical in-use stability after reconstitution and subsequent dilution in the solvent

has been demonstrated for 4 hours when stored at 2 to 8

In order to avoid the potential contamination of the medicine by microbes, the product should

be used immediately.

If the medicine is not used immediately, it should be kept at a temperature of 2 to 8

C (in the

refrigerator) and no longer than 4 hours.

5.

DISPOSAL

All items for preparation, administration or cleaning, including gloves, as well as liquid waste should

be disposed of in accordance with local requirements.