Cardioxane

Package Leaflet: Information for the Patient

Cardioxane, 500 mg, Powder for Solution for Infusion

Dexrazoxane

Read the Package Leaflet Carefully Before Using the Medication, as it Contains Important Information for the Patient.

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

Table of Contents of the Package Leaflet:

• 1. What is Cardioxane and What is it Used For
• 2. Important Information Before Using Cardioxane
• 3. How to Use Cardioxane
• 4. Possible Side Effects
• 5. How to Store Cardioxane
• 6. Package Contents and Other Information

1. What is Cardioxane and What is it Used For

Cardioxane contains the active substance dexrazoxane. This substance belongs to a group of
medicines that protect the heart (cardioprotective medicines).
Cardioxane is used to prevent heart damage in adult patients with breast cancer who are being treated with anthracyclines (doxorubicin or epirubicin).

2. Important Information Before Using Cardioxane

When Not to Use Cardioxane

Warnings and Precautions

Before starting treatment with Cardioxane, discuss it with your doctor

Be Aware That:

• your doctor may order tests before or during treatment with Cardioxane to check the effectiveness of the treatment and the functioning of certain organs, such as the heart, kidneys, or liver;
• your doctor may order blood tests during treatment with Cardioxane to monitor bone marrow function. If you are being treated with high doses of anticancer medications (e.g., chemotherapy or radiation) and also receiving high doses of Cardioxane, bone marrow function may be impaired. This condition 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 of childbearing age and men should use effective contraception methods. Women and men should use contraception for at least six months after the end of treatment with Cardioxane (see also “Pregnancy and Breastfeeding”);
• combined treatment with Cardioxane and anticancer medications may increase the risk of blood clots;
• , inform your doctor immediately. The patient or doctor should immediately rinse the area with water.

Children and Adolescents

The long-term benefits and risks associated with the use of this medication in children and adolescents are not yet clear. The doctor will discuss the benefits and risks associated with the use of this medication.

Patients Over 65 Years Old

The doctor may adjust the treatment with Cardioxane depending on the patient's health status (in case of heart, liver, or kidney problems).

Cardioxane and Other Medications

Inform your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take.
It is not recommended to use other medications without consulting your doctor, due to the possibility of interactions between Cardioxane and other medications:

• vaccines: do not use Cardioxane if a yellow fever vaccine is to be administered, and it is not recommended to use Cardioxane if a vaccine containing live virus particles is to be administered;
• phenytoin: antiepileptic treatment;
• cyclosporine or tacrolimus: medications that suppress the immune system and are used to prevent transplant rejection after organ transplantation
• myelosuppressive medications: medications that reduce the production of red blood cells, white blood cells, and platelets.

Pregnancy and Breastfeeding

• Pregnant or breastfeeding women should not receive Cardioxane, unless the doctor decides it is necessary.
• Women of childbearing age and men should use effective contraception methods during treatment with Cardioxane and for at least six months after the end of treatment.
• During treatment with Cardioxane, breastfeeding should be discontinued. If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult her doctor or pharmacist before taking this medication.

Driving and Operating Machines

During treatment with Cardioxane, fatigue has been reported. Therefore, if the patient feels drowsy, they should not drive or operate machines.

3. How to Use Cardioxane

How Cardioxane is Administered to the Patient

This medication will be prepared and administered to the patient by a doctor or other medical staff. The dose administered to the patient is determined by the doctor.

• Cardioxane is administered by intravenous infusion (infusion) lasting approximately 15 minutes. The infusion is started about 30 minutes before the administration of the anticancer medication (doxorubicin and/or epirubicin).

Possible Use of a Higher Than Recommended Dose of Cardioxane

If the patient receives too much Cardioxane, they should inform their doctor or nurse immediately. Some of the side effects listed in section 4, "Possible Side Effects," may occur.

4. Possible Side Effects

Like all medications, Cardioxane can cause side effects, although not everyone will experience them.

Some Side Effects May be Serious and Require Immediate Medical Attention:

Very Common(may occur more frequently than in 1 in 10 patients):

• Frequent infections, fever, sore throat, unexpected bruising, and bleeding (symptoms of blood disorders such as low red blood cell count, low white blood cell count, low platelet count, and low granulocyte count. However, after each treatment cycle, blood test results may return to normal) Common(may occur less frequently than in 1 in 10 patients):
• Swelling and redness of the vein Uncommon(may occur less frequently than in 1 in 100 patients):
• Leukemia (blood cancer)
• Sudden loss of consciousness
• Swelling and pain in one part of the body, which may be caused by a blood clot in a vein
• Swelling of limb tissues

During treatment with Cardioxane, a few patients have reported the following side effects:

• Allergic reactions, including itching, rash, swelling of the face/throat, wheezing, shortness of breath, or difficulty breathing, changes in consciousness, low blood pressure
• Sudden shortness of breath, coughing up blood, and chest pain (symptoms of a blood clot in the lung)

If Any of the Above Symptoms Occur, Inform Your Doctor or Nurse Immediately or Go to the Emergency Room of the Nearest Hospital.

Other Side Effects Include:

Very Common(may occur more frequently than in 1 in 10 patients):

• Hair loss
• Vomiting, mouth ulcers, nausea
• Weakness Common(may occur less frequently than in 1 in 10 patients):
• Diarrhea, abdominal pain, constipation, feeling of fullness in the stomach, and loss of appetite
• Weakness of heart function, rapid heartbeat
• Pain, redness, and swelling of the mucous membranes of internal passages such as the respiratory tract or esophagus
• Nail disorders such as blackening
• Skin reaction such as swelling, redness, pain, burning sensation, itching at the injection site
• Numbness and tingling of hands or feet, dizziness, headache
• Feeling of fatigue, general malaise
• Slight increase in body temperature, chest pain, and/or increased heart rate, shortness of breath or gasping for air
• Abnormal liver function test results Uncommon(may occur less frequently than in 1 in 100 patients)
• Increased blood cell count
• Dizziness, ear infections
• Bleeding, sensitivity, or swelling of the gums, thrush
• Thirst
• Redness, excessive heat, and tenderness due to subcutaneous inflammation

Reporting Side Effects

If You Experience Any Side Effects, Including Those Not Listed in This Package Leaflet, Inform Your Doctor, Pharmacist, or Nurse.

Side effects can be reported directly to:
Department of Adverse Reaction Monitoring of Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: ndl@urpl.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help gather more information on the safety of the medication.

5. How to Store Cardioxane

• Store the medication in a place inaccessible and invisible to children.
• Do not store above 25°C. Store in the original packaging to protect from light.
• Do not use this medication after the expiration date stated on the packaging.
• Medications should not be disposed of in wastewater or household waste. Ask your pharmacist how to dispose of unused medications or those that are no longer needed. This will help protect the environment.

6. Package Contents and Other Information

What Cardioxane Contains

• The active substance of Cardioxane is dexrazoxane (in the form of dexrazoxane hydrochloride).
• Each vial contains 500 mg of dexrazoxane. Cardioxane does not contain other ingredients.

What Cardioxane Looks Like and What the Package Contains

Cardioxane is available as a white or almost white lyophilized powder,
in a package containing one vial.

Marketing Authorization Holder

Clinigen Healthcare B.V.
Schiphol Boulevard 359
WTC Schiphol Airport, D Tower 11th floor
1118BJ Schiphol
Netherlands

Manufacturer

Cenexi Laboratoires Thissen S.A.
Rue de la Papyrée 2-4-6

• B - 1420 Braine-l’Alleud Belgium

Date of Last Update of the Package Leaflet:

11/2018

INFORMATION INTENDED EXCLUSIVELY FOR MEDICAL PROFESSIONALS

Cardioxane, 500 mg, Powder for Solution for Infusion

Dexrazoxane

DOSAGE AND ADMINISTRATION

Cardioxane is administered by short-term intravenous infusion (15 minutes) approximately 30 minutes before the administration of anthracyclines at a dose equivalent to 10 times the dose of doxorubicin or 10 times the dose of epirubicin.
The recommended dose of Cardioxane is 500 mg/m² in a commonly used doxorubicin dosing regimen of 50 mg/m² or 600 mg/m² in a commonly used epirubicin dosing regimen of 60 mg/m².

Children and Adolescents

The safety and efficacy of Cardioxane have not been established in children from 0 to 18 years of age.
Cardioxane is contraindicated in children from 0 to 18 years of age who are scheduled to receive a cumulative dose of doxorubicin less than 300 mg/m² or an equivalent cumulative dose of another anthracycline.

Patients with Renal Impairment

In cases of moderate to severe renal impairment (creatinine clearance <40 ml min), the dose of dexrazoxane should be reduced by 50%.< p>

Patients with Hepatic Impairment

In these patients, the dose of dexrazoxane should be maintained in proportion to the dose of anthracyclines, e.g., by reducing the dose of dexrazoxane in proportion to the reduction of the anthracycline dose.

Elderly Patients (Over 65 Years Old)

The dose can be adjusted in case of treatment with Cardioxane, depending on the patient's health status (in case of heart, liver, or kidney problems).
In case of overdose, symptomatic treatment should be applied.

INSTRUCTIONS FOR PREPARING CARDIOXANE FOR USE

General Recommendations for Safe Handling

The medication should be reconstituted only by trained personnel in a specially designated area. This procedure should not be performed by pregnant women. The use of gloves and other protective clothing is recommended to protect the skin. Skin reactions have been reported following contact with Cardioxane. If Cardioxane in powder or solution form comes into contact with the skin or mucous membranes, it should be rinsed immediately with water.

Preparation of the Solution for Intravenous Infusion

Reconstitution of Cardioxane
The contents of the vial should be dissolved in 25 ml of water for injection. The contents of the vial dissolve within a few minutes with gentle shaking. The resulting solution has a pH of approximately 1.6. It should be diluted before administration to the patient.
Dilution of Cardioxane
To avoid the risk of thrombophlebitis at the injection site, the solution should be diluted before infusion with one of the following solutions. The use of solutions with a higher pH is recommended. The final volume of the solution is proportional to the number of vials of Cardioxane and the volume of the solution used for dilution; it ranges from 25 ml to 100 ml per vial.
The table shows the final volume and approximate pH of the reconstituted and diluted Cardioxane, depending on the use of 1 or 4 vials. The following solutions are recommended:

*
11.2% sodium lactate solution should be diluted six times to obtain a concentration of 0.16 M.
To increase the pH of Cardioxane, it is recommended to use a larger volume of solution (up to 100 ml of solution per 25 ml of reconstituted Cardioxane). If necessary and justified by the patient's hemodynamic status, smaller volumes of solution can be used (at least 25 ml of solution per 25 ml of reconstituted Cardioxane).
The reconstituted and diluted Cardioxane is intended for single use. After reconstitution and dilution, the product should be used immediately or within 4 hours if stored at a temperature between 2°C and 8°C (in a refrigerator).
Medications intended for parenteral administration should be visually inspected for the presence of foreign particles and changes in color before administration. Immediately after reconstitution, the Cardioxane solution should be colorless to yellow, but it may change over time, which does not necessarily mean a loss of its potency if it has been stored properly. However, if the solution has a different color than described above after dissolution, it should be discarded.

Incompatibilities

Cardioxane should not be mixed with other medications and solvents, except for those listed above.

Storage

Do not use Cardioxane after the expiration date stated on the packaging.
Before Opening
Do not store above 25°C. Store in the original packaging to protect from light.
After Reconstitution and Dilution
Cardioxane, after dissolution in water for injection and dilution, remains stable for 4 hours at a temperature below 25°C.
From a microbiological point of view, Cardioxane, after reconstitution and dilution, should be used immediately.
If Cardioxane is not used immediately, it can be stored without access to light at a temperature between 2°C and 8°C (in a refrigerator), but no longer than 4 hours – for which the person administering the medication is responsible.

Disposal of Unused Medication

Any unused product or waste material should be disposed of in accordance with local regulations. Particular attention should be paid and appropriate precautions taken when disposing of items used for the reconstitution and dilution of Cardioxane.