Cardioxane

Package leaflet: Information for the patient

CARDIOXANE 500 mg powder for solution for infusion

Dexrazoxane
Please read all of this leaflet carefully before taking 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, pharmacist or nurse.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Cardioxane is and what it is used for

Cardioxane contains a substance called dexrazoxane. This substance belongs to a group of
medicines that protect the heart (cardioprotective medicines).
Cardioxane is used to prevent heart damage when medicines called anthracyclines (such as
doxorubicin or epirubicin) are used during the treatment of breast cancer in adult patients.

2. What you need to know before taking Cardioxane

Do not take Cardioxane

• if you are under 18 years of age and your planned dose of anthracyclines is considered low – discuss this with your doctor.
• if you are allergic (hypersensitive) to dexrazoxane.
• if you are breastfeeding (see also “Pregnancy and breastfeeding”).
• if you are receiving the yellow fever vaccine. If any of the conditions listed above apply to you, do not take this medicine.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking 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, or heart valve problems.
• if you are pregnant or planning to become pregnant (see also “Pregnancy and breastfeeding”).
• if you are allergic to dexrazoxane.

You should also know that:

• Your doctor may perform tests before and during treatment with Cardioxane to monitor how the treatment is working and to check the function of certain organs such as the heart, kidneys, or liver.
• During treatment with Cardioxane, your doctor may carry out blood tests to monitor bone marrow function. If you are receiving high doses of anticancer treatment (e.g., chemotherapy or radiotherapy) and are also being treated with high doses of Cardioxane, bone marrow function may be reduced. This could 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 potential and men must use an effective contraceptive method. Women and men must continue using contraception for at least six months after stopping treatment with Cardioxane (see also “Pregnancy and breastfeeding”).
• The combination of Cardioxane with cancer treatment may increase the risk of blood clots.
• If the Cardioxane powder or solution comes into contact with the skin, inform your doctor immediately. You or your doctor must immediately rinse the affected area thoroughly with water.

Children and adolescents
The long-term benefits and risks of this medicine in children and adolescents are not yet clear. Your doctor will provide guidance on the benefits and risks of this medicine.
Elderly patients (over 65 years)
Your doctor may adjust treatment with Cardioxane according to your health status (in case of heart, liver, or kidney problems).
Other medicines and Cardioxane
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is not advisable to take other medicines without informing your doctor, as interactions may occur between Cardioxane and other medicines:

• vaccines: you must not use Cardioxane if receiving the yellow fever vaccine, and it is not recommended to use Cardioxane if receiving a vaccine containing live virus particles;
• phenytoin, a treatment for seizures;
• cyclosporine or tacrolimus (both used for immunosuppression and to prevent organ rejection after transplantation);
• myelosuppressive medicines (which reduce the production of white blood cells, red blood cells, and platelets).

Pregnancy and breastfeeding

• You must not take Cardioxane if you are pregnant or planning to become pregnant, unless your doctor decides it is necessary.
• Women of childbearing potential and men must use an effective contraceptive method during treatment with Cardioxane and for at least six months after treatment with Cardioxane has been stopped.
• Stop breastfeeding while receiving treatment with Cardioxane. If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before this medicine is administered.

Driving and using machines
Fatigue has been reported during treatment with Cardioxane. Therefore, if you feel drowsy, do not drive and do not operate machinery.

3. How to administer Cardioxane

How Cardioxane will be administered to you
This medicine is prepared to be administered by a doctor or medical personnel.
The dose you will receive is determined by your doctor.

• Cardioxane is given as an intravenous infusion over approximately 15 minutes.
• This will begin approximately 30 minutes before your cancer treatment (doxorubicin and/or epirubicin).

If you are given more Cardioxane than you should
If you have been given too much Cardioxane, inform your doctor or healthcare professional immediately.
Some of the side effects listed in section 4, “Possible side effects”, may occur.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Some side effects can be serious and require immediate medical attention:
Very common (may affect more than 1 in 10 people):

• Frequent infections, fever, sore throat, unexpected bruising and bleeding (signs of blood disorders such as low red blood cell count, low white blood cell count, low platelet count and low granulocyte levels. Blood counts may, however, return to normal after each treatment cycle).
  Common (may affect up to 1 in 10 people):
• Swelling and redness of a vein
  Uncommon (may affect up to 1 in 100 people):
• Leukaemia (blood cancer)
• Sudden loss of consciousness
• Swelling and pain in part of the body that may be caused by blood clotting within a vein
• Swelling of the tissues of the limbs

The following side effects have been reported in very few patients during treatment with Cardioxane:

• Allergic reactions with itching, skin rash, facial/throat swelling, wheezing, shortness of breath or difficulty breathing, changes in level of consciousness, hypotension
• Sudden onset of shortness of breath, coughing up blood and chest pain (signs of blood clots in the lungs)
  If you notice any of the above-listed side effects, inform your doctor immediately or go to the nearest emergency room.

Other side effects include:
Very common (may affect more than 1 in 10 people):

• Hair loss
• Vomiting, mouth sores, nausea
• Weakness
  Common (may affect up to 1 in 10 people):
• Diarrhoea, stomach pain, constipation, feeling of fullness in the stomach and loss of appetite
• Reduced heart muscle function, rapid heartbeat
• Pain, redness and swelling of the mucous membranes of internal passages such as the respiratory tract or the oesophagus
• Nail disorders such as blackening
• Skin reactions such as swelling, redness, pain, burning sensation, itching at the injection site
• Tingling or numbness in hands or feet, dizziness, headache
• Fatigue, general feeling of malaise
• Mild fever, chest pain, increased/accelerated heartbeat, shortness of breath or laboured breathing
• Abnormal liver function tests
  Uncommon (may affect up to 1 in 100 people):
• Increased blood cell count
• Dizziness, ear infection
• Bleeding, tender or swollen gums, oral thrush
• Thirst
• Skin red, warm and soft to touch due to subcutaneous inflammation

Reporting of side effects
If you get any side effects, including any not listed in this leaflet, talk to your doctor, pharmacist or nurse.
You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Cardioxane

• Keep this medicine out of the sight and reach of children.
• Do not store above 25°C. Store in the original packaging to protect the medicine from light.
• Do not use this medicine after the expiry date stated on the carton.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Cardioxane contains

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

Description of the appearance of Cardioxane and contents of the pack
Cardioxane is a white to almost white powder for solution for infusion, available in packs containing one vial.
Marketing Authorisation Holder and Manufacturer
CNX Therapeutics Ireland Limited
5 Floor Rear, Connaught House
1 Burlington Road
Dublin 4
Ireland
Manufacturer
Cenexi Laboratoires Thissen S.A.
Rue de la Papyrée 2-4-6
1420 Braine-l’Alleud
Belgium
THE FOLLOWING INFORMATION IS INTENDED EXCLUSIVELY FOR
HEALTHCARE PROFESSIONALS
CARDIOXANE 500 mg powder for solution for infusion
Dexrazoxano
DOSAGE AND METHOD OF ADMINISTRATION
Cardioxane is administered by short intravenous infusion (15 minutes), approximately 30 minutes before the administration of anthracyclines, at a dose equal to 10 times the equivalent dose of doxorubicin and 10 times the equivalent dose of epirubicin.
Therefore, it is recommended that Cardioxane be administered at a dose of 500 mg/m² when the normally used dose of doxorubicin is 50 mg/m², or at 600 mg/m² when the commonly used dose of epirubicin is 60 mg/m².
Paediatric population
In children aged between 0 and 18 years, the safety and efficacy of Cardioxane have not yet been established.
Cardioxane is contraindicated in children aged between 0 and 18 years who are expected to receive a cumulative dose of less than 300 mg/m² of doxorubicin or the equivalent cumulative dose of another anthracycline.
Renal impairment
In patients with moderate to severe renal dysfunction (creatinine clearance < 40 ml/min), the dexrazoxane dose should be reduced by 50%.
Hepatic impairment
The dosing ratio should be maintained; for example, if the anthracycline dose is reduced, the dexrazoxane dose should also be reduced accordingly.
Elderly patients (over 65 years)
Dosage during treatment with Cardioxane may be adjusted according to the patient's health status (e.g. in case of cardiac, hepatic or renal problems).
In case of overdose, symptomatic treatment should be administered.
INSTRUCTIONS FOR USE
Recommendations for safe use
Prescribers must refer to national or otherwise recognised guidelines for handling cytotoxic agents when using Cardioxane. Reconstitution must be performed only by trained personnel in a designated area for handling cytotoxic agents. Preparation must not be carried out by pregnant personnel.
Use of gloves and other protective clothing is recommended to prevent skin contact.
Skin reactions following contact with Cardioxane have been reported. If the powder or solution of Cardioxane comes into contact with the skin or mucous membranes, the affected area must be immediately and thoroughly rinsed with water.
Preparation for intravenous administration
Reconstitution of Cardioxane
For reconstitution, the contents of each vial must be dissolved in 25 ml of water for injections. The vial contents will dissolve within a few minutes with gentle shaking. The resulting solution has a pH of approximately 1.6. This solution must be further diluted before administration to the patient.
Dilution of Cardioxane
To avoid the risk of thrombophlebitis at the injection site, Cardioxane must be diluted prior to infusion with one of the solutions listed in Table 1. The final volume is proportional to the number of Cardioxane vials used and the amount of infusion fluid used for dilution, which may range between 25 ml and 100 ml per vial.
The table below summarises the final volume and approximate pH of the reconstituted and diluted product for one vial and for four vials of Cardioxane. The minimum and maximum volumes of infusion fluid to be used are shown in Table 1.
Table 1. Reconstitution and dilution of one vial of Cardioxane

* Sodium lactate 11.2% must be diluted by a factor of 6 to achieve a concentration of
0.16 M.
It is generally recommended to use large dilution volumes (up to a maximum of 100 ml
of infusion fluid added for each 25 ml of reconstituted Cardioxane) in order to increase the pH
of the solution. If necessary, based on the patient's hemodynamic conditions, smaller dilution volumes may be
used (down to a minimum of 25 ml of infusion fluid added for each 25 ml of reconstituted Cardioxane).
Once reconstituted and diluted, Cardioxane is for single use only. The diluted solution must be used immediately or stored for no more than 4 hours between +2 °C and +8 °C and protected from light.
Parenteral products should be inspected visually for particulate matter and discoloration, if the solution and container permit. Cardioxane is normally a solution ranging from colourless to yellow immediately after reconstitution, but some variation in colour may be observed over time and is not indicative of loss of activity if the product has been stored according to recommendations. However, the product should be discarded if the colour immediately after reconstitution is not from colourless to yellow.
Incompatibilities
Cardioxane must not be mixed with other medicinal products except for the dilution solutions listed above.
Storage
Do not use Cardioxane after the expiry date stated on the carton.
Before opening
Do not store above 25°C. Keep Cardioxane vials in the original packaging to protect the medicinal product from light.
After reconstitution and dilution
The diluted solution of Cardioxane is physically and chemically stable for 4 hours at 25°C.
From a microbiological standpoint, the infusion solution prepared for use should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user. Storage times must not exceed 4 hours at temperatures between 2°C and 8°C (in a refrigerator), protected from light.
Disposal
Unused medicine and waste materials derived from this medicine must be disposed of in accordance with local regulations. Appropriate care and caution must be taken in the disposal of materials used for the reconstitution and dilution of Cardioxane.