Patient Information Leaflet

Cardioxane500 mg powder for solution for infusion

Dexrazoxane

Read this leaflet carefully before you start taking this medicine, as it contains important information for you.

−Keep this leaflet, as you may need to read it again.

−If you have any questions, consult your doctor, pharmacist or nurse.

−If you experience any side effects, consult your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Cardioxanecontains the active ingredient called dexrazoxane, which belongs to a group of medications that protect the heart (cardioprotective medications).

This medicationis used to prevent heart damage when the medications calledanthracyclines (such asdoxorubicin or epirubicin) are used during cancer treatment of breast cancer in adults.

Do not administerCardioxane

• if you are under 18 years old and the planned dose of anthracycline is considered low. Consult your doctor about this.
• if you are allergic (hypersensitive) to dexrazoxane
• if you are breastfeeding (also see “Pregnancy and breastfeeding”)
• if you are being administered the yellow fever vaccine

if you are in any of these cases, do not administer this medication.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before receiving Cardioxane

• if you have or have had liver or kidney problems.
• if you have or have had a heart attack, heart failure, uncontrolled chest pain, and heart valve problems.
• if you are pregnant or plan to become pregnant (also see “Pregnancy and breastfeeding”).
• if you are allergic to dexrazoxane.

You should also know that:

• Your doctor may perform checks before and during treatment with this medication to see how you respond to treatment and monitor the function of some organs, such as the heart, kidneys, or liver.
• Your doctor may perform blood tests during treatment with Cardioxane to monitor the function of your bone marrow. If you are receiving high-dose cancer treatment (e.g., chemotherapy or radiation) and also being treated with high doses of Cardioxane, there may be a decrease in the function of your bone marrow. This can affect the production of red blood cells, white blood cells, and platelets.
• Cardioxane may increase the risk of developing leukemia (blood cancer).
• During treatment with Cardioxane, women who may become pregnant and men should use effective contraceptive methods. Women and men should continue to use them for at least six months after completing treatment with Cardioxane (also see “Pregnancy and breastfeeding”).
• The combination of Cardioxane with the cancer treatment you are receiving may increase the risk of blood clots.
• In the case that Cardioxane powder or solution comes into contact with the skin,inform your doctor immediately. You or your doctor should wash the affected area immediately with plenty of water.

Children and adolescents

The long-term benefit-risk relationship of the medication in children and adolescents is not yet clear. Your doctor will inform you of the benefit-risk relationship of this medication.

Older patients (over 65 years)

Your doctor may adjust your treatment with this medication according to your health status (in case of heart, liver, or kidney problems).

Other medications and Cardioxane

Inform your doctor or pharmacist if you are taking, have taken recently, or may take any other medication.

Do not take other medications without informing your doctor, as there may be interactions between Cardioxane and other medications:

• Vaccines: do not use this medication if you are to be administered the yellow fever vaccine and do not recommend using Cardioxane if you are to be administered a vaccine that contains live virus particles.
• Phenytoin, a treatment for seizures.
• Ciclosporin or tacrolimus (both treatments reduce the body's immune system and are used to prevent organ rejection after an organ transplant).
• myelosuppressive medications (reduce the production of red blood cells, white blood cells, or platelets).

Pregnancy and breastfeeding

• Do not administer Cardioxane if you are pregnant or plan to become pregnant, unless your doctor considers it necessary.
• Women who may become pregnant and men should use effective contraceptive methods during treatment with Cardioxane and for at least six months after completing treatment with Cardioxane.
• Stop breastfeeding while on treatment with this medication.

If you are pregnant or breastfeeding, or think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before receiving this medication.

Driving and operating machinery

There have been reports of fatigue with treatment with Cardioxane. Therefore, if you feel drowsy, do not drive or operate machinery.

How You Will Be GivenCardioxane

This medication is prepared and administered by a doctor or other healthcare professional. Your doctor will decide what dose you should receive.

• Cardioxaneis administered as an infusion (perfusion) through a vein for approximately 15minutes.
• The administration will begin approximately 30minutes before your cancer treatment (doxorubicin and/or epirubicin) is administered.

If You Think You Have Been Given Too MuchCardioxane

If you are given too muchCardioxane, inform your doctor or nurse immediately. You may experience some of the adverse effects listed in section 4, “Possible Adverse Effects”.

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

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

Very common(may affect more than 1 in 10 patients):

−Frequent infections, fever, sore throat, bruising and unexpected bleeding (signs of blood abnormalities such as low red blood cell count, low white blood cell count, low platelet count, and low granulocyte count. However, blood cell levels may return to normal after each treatment cycle)

Common(may affect up to 1 in 10 patients):

−Swelling and redness in a vein

Rare(may affect up to 1 in 100 patients):

−Leukemia (blood cancer)

−Sudden loss of consciousness

−Swelling and pain in a part of the body that may be caused by blood clots in a vein

−Swelling of the tissue in the legs

The followingadverse reactions have been reported in very few patients during treatment with Cardioxane:

−Allergic reactions that include itching, rash, swelling of the face/throat, wheezing, difficulty breathing, changes in levels of consciousness, low blood pressure

−Sudden onset of difficulty breathing, coughing up blood, and chest pain (signs of blood clots in the lungs)

If you experience any of the side effects described above, inform your doctor immediately or visit the nearest emergency service.

Other side effects include:

Very common(may affect more than 1 in 10 patients):

−Hair loss

−Vomiting, mouth sores, nausea

−Weakness

Common(may affect up to 1 in 10 patients):

−Abnormal liver function tests

Rare(may affect up to 1 in 100 patients)

Reporting of side effects

If you experienceany type of side effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect that does not appear in this prospectus.

You can also report them directly throughthe Spanish System for the Pharmacovigilance of Medicines for Human Use: https://www.notificaram.es.By 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 store at a temperature above 25°C. Store in the original packaging to protect it from light.
• Do not usethis medicationafter the expiration date that appears on thecontainer after CAD.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of unused medicines. By doing so, you will help protect the environment.

Composition ofCardioxane

• The active principle is dexrazoxane (as hydrochloride of dexrazoxane).
• Each vial contains 500 mg of dexrazoxane. Cardioxane does not contain other components.

Appearance ofCardioxaneand contents of the container

Cardioxane is a white to off-white powder for solution for infusion, available in vials and containers of four vials.Only some sizes of containers may be marketed.

Marketing Authorization Holder

CNX Therapeutics Ireland Limited

5th Floor Rear

Connaught House

1 Burlington Road

Dublin 4

Dublin, Ireland

Manufacturer

Cenexi Laboratoires Thissen S.A.

Rue de la Papyrée 2-4-6

1420 Braine-l’Alleud

Belgium

Last review date of this leaflet:22/08/2017.

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es

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THIS INFORMATIONIS INTENDED ONLY FORHEALTHCARE PROFESSIONALS

Cardioxane500mg powder for solution for infusion

Dexrazoxane

POSOLLOGY AND ADMINISTRATION ROUTE

Cardioxane is administered by a short intravenous infusion (15 minutes), approximately 30 minutes before the administration of anthracycline, with a dose equal to 10 times the equivalent of doxorubicin and 10 times the equivalent dose of epirubicin.

Therefore, it is recommended to administer Cardioxane at a dose of 500mg/m2when using the usual dosing regimen of doxorubicin of 50mg/m2,or at a dose of 600mg/ m2when using the usual dosing regimen of epirubicin of 60mg/m2.

Pediatric population

The safety and efficacy of this medicine have not been established in children from 0 to 18years.

Cardioxane is contraindicated in children from 0 to 18years who are expected to receive a cumulative dose of less than 300mg/m2of doxorubicin or the equivalent cumulative dose of another anthracycline.

Renal insufficiency

In patients with moderate to severe renal insufficiency (creatinine clearance <40ml

Insuficiency

The dose ratio should be maintained; that is, if the anthracycline dose is reduced, the dexrazoxane dose should be reduced accordingly.

Geriatric population (65years and older)

The dose may be adjusted during treatment with Cardioxane according to the patient's health status (in case of heart, liver, or kidney problems).

In case of overdose, symptomatic treatment should be applied.

ADMINISTRATION INSTRUCTIONS

Recommendations for safe handling

Prescribers should consult national or recognized guidelines on the handling of cytotoxic agents when using Cardioxane. Reconstitution should only be performed by trained personnel in a designated cytotoxic area. Pregnant women should not handle the preparation.

It is recommended to use gloves and other protective clothing to avoid skin contact. Skin reactions have been described after contact with Cardioxane. In case of direct contact with the skin or mucous membranes, wash the affected area immediately with plenty of water.

Preparation for intravenous administration

Reconstitution of Cardioxane

To reconstitute, the contents of each vial should be dissolved in 25 ml of water forinjection. The contents of the vial should dissolve in a few minutes by gently agitating. The resulting solution has a pH of approximately 1.6. This solution should be further diluted before administration to the patient.

Dilution ofCardioxane

To avoid the risk of thrombophlebitis at the injection site, Cardioxane should be diluted before infusion with one of the solutions listed in Table 1. The final volume should be proportional to the number of vials of Cardioxane used and the amount of infusion solution for dilution, which can range from 25 ml to 100 ml per vial.

The following table (Table 1) summarizes the final volume and approximate pH of the reconstituted and diluted product of a vial and four vials of Cardioxane. The minimum and maximum volumes of infusion solution to be used per vial are indicated in Table 1.

Table 1. Reconstitution and dilution of vials of Cardioxane

• Lactate sodium 11.2% should be diluted with a factor of 6 to achieve a concentration of 0.16M.

It is recommended to use larger volumes of dilution (with a maximum of 100 ml of infusion solution additional per 25 ml of reconstituted Cardioxane) to increase the pH of the solution. Smaller volumes (with a minimum of 25 ml of infusion solution additional per 25 ml of reconstituted Cardioxane) may be used, if necessary, depending on the patient's hemodynamic status.

The Cardioxane solution reconstituted and diluted is for single use. Once the product has been diluted, it should be used immediately or within four hours, provided it is stored at a temperature between 2°C and 8°C and protected from light.

In cases where the solution and its container allow, parenteral medications should be visually inspected to check for any lumps or particles. Cardioxane usually presents as a colorless to yellow solution immediately after reconstitution, although some color variability may occur over time, which does not indicate loss of activity as long as the product has been stored in accordance with the recommended storage conditions. However, it is recommended to discard the product if it is not colorless or yellow immediately after reconstitution.

Incompatibilities

Cardioxane should not be mixed with other products except for the solutions for dilution mentioned above.

Storage

Do not use Cardioxane after the expiration date indicated on the container.

Before opening

Do not store at a temperature above 25°C. Store in the original packaging to protect it from light.

After reconstitution and dilution

The diluted Cardioxane solution is physically and chemically stable for 4 hours at 25°C.

From a microbiological point of view, the freshly prepared infusion solution should be used immediately. Otherwise, the responsibility for the storage time and the conditions of the product before administration falls on the user, and in any case, it should not exceed 4 hours at a temperature between 2°C and 8°C (in the refrigerator), with protection from light.

Disposal

The disposal of used medication and materials that have come into contact with it should be carried out in accordance with local regulations. Care should be taken and precautions should be taken when disposing of used items for reconstituting and diluting Cardioxane.