CYRDANAX 20 mg /Ml Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Cyrdanax 20 mg/ml, powder for solution for infusion
   1. Read the leaflet carefully before using the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet
3. What is Cyrdanax and what is it used for
4. Important information before using Cyrdanax
   1. When not to use Cyrdanax:
   2. Warnings and precautions
   3. Be aware that:
   4. Children and adolescents
   5. Patients over 65 years of age
   6. Cyrdanax and other medicines
   7. Pregnancy and breastfeeding
   8. Driving and using machines
5. How to use Cyrdanax
   1. How Cyrdanax is administered to the patient
   2. Possible overdose of Cyrdanax
6. Possible side effects
   1. Some side effects may be serious and require immediate medical attention:
   2. If any of the above symptoms occur, the patient should immediately inform their doctor or go to the emergency room.
   3. Other side effects include:
   4. Reporting side effects
7. How to store Cyrdanax
8. Contents of the packaging and other information
   1. What Cyrdanax contains
   2. What Cyrdanax looks like and what the packaging contains:
   3. Marketing authorization holder
   4. Manufacturer
   5. This medicine is authorized in the Member States of the European Economic Area under the following names:
   6. The following information is intended for healthcare professionals only
   7. Preparation of the solution for intravenous infusion
   8. Vials 500 mg:
   9. Vials 250 mg:
   10. Infusion fluid used for dilution
   11. Volume of fluid used for dilution of 1 vial of dissolved Cyrdanax
   12. Final volume of 1 vial
   13. Final volume of 4 vials
   14. Storage instructions

Leaflet accompanying the packaging: patient information

Cyrdanax 20 mg/ml, powder for solution for infusion

(Dexrazoxane)

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor or pharmacist.
• If the patient experiences any side effects, including those not listed in this leaflet, they should inform their doctor or pharmacist. See section 4.

Table of contents of the leaflet

• 1. What is Cyrdanax and what is it used for
• 2. Important information before using Cyrdanax
• 3. How to use Cyrdanax
• 4. Possible side effects
• 5. How to store Cyrdanax
• 6. Contents of the packaging and other information

1. What is Cyrdanax and what is it used for

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

2. Important information before using Cyrdanax

When not to use Cyrdanax:

• if the patient is under 18 years of age and the planned dose of anthracycline is considered low - consult a doctor; if the patient is hypersensitive to dexrazoxane;
• if the patient is breastfeeding (see also "Pregnancy and breastfeeding");
• if the patient has received a yellow fever vaccine. If any of these situations occur, the patient should not receive this medicine.

Warnings and precautions

Before starting treatment with Cyrdanax, discuss with your doctor:

• if the patient has or has had liver or kidney disease in the past;
• if the patient has or has had a heart attack, heart failure, untreated chest pain, and heart valve diseases;
• if the patient is pregnant or planning to become pregnant (see also "Pregnancy and breastfeeding");
• if the patient is allergic to dexrazoxane.

Be aware that:

• the doctor may order tests before or during treatment with Cyrdanax to check the effectiveness of the treatment and the function of certain organs, such as the heart, kidneys, or liver;
• the doctor may order blood tests during treatment with Cyrdanax to monitor bone marrow function. If the patient is receiving anticancer treatment with high doses (e.g., chemotherapy or radiation) and is also taking high doses of Cyrdanax, bone marrow function may be impaired. This condition can affect the production of red blood cells, white blood cells, and platelets;
• Cyrdanax may increase the risk of leukemia (blood cancer);
• during treatment with Cyrdanax, women of childbearing age and men should use effective contraception methods. Men should use methods to prevent conception for at least six months after the end of treatment with Cyrdanax (see also "Pregnancy and breastfeeding");
• combined treatment with Cyrdanax and anticancer medicines may increase the risk of blood clots;
• if Cyrdanax in powder or solution form comes into contact with the skin, the patient should immediately inform their doctor. The patient or doctor should immediately rinse the area with water.

Children and adolescents

The long-term benefits and risks of using this medicine in children and adolescents are not yet clear. The doctor will inform about the benefits and risks associated with the use of this medicine.

Patients over 65 years of age

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

Cyrdanax and other medicines

Inform your doctor or pharmacist about all medicines being taken or used by the patient currently or recently, as well as any medicines the patient plans to take or use. It is not recommended to take other medicines without consulting the attending doctor, due to the possibility of interactions between Cyrdanax and other medicines:

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

Pregnancy and breastfeeding

• If the patient is pregnant or breastfeeding, suspects they may be pregnant, or plans to have a child, they should consult a doctor or pharmacist before using this medicine.
• Pregnant or planning-to-become-pregnant patients will not receive Cyrdanax unless the doctor decides it is necessary.
• Women of childbearing age and men should use effective contraception methods during treatment with Cyrdanax and for at least six months after the end of treatment with Cyrdanax.
• During treatment with Cyrdanax, breastfeeding should be discontinued.

Driving and using machines

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

3. How to use Cyrdanax

How Cyrdanax is administered to the patient

This medicine will be prepared and then administered to the patient by a doctor or other medical personnel. The dose administered to the patient is determined by the doctor. Cyrdanax is administered by intravenous infusion lasting about 15 minutes. The infusion is started about 30 minutes before the administration of the anticancer medicine [doxorubicin and/or epirubicin].

Possible overdose of Cyrdanax

If the patient receives too much Cyrdanax, they should immediately inform their doctor or nurse. 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 everybody gets them.

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

Very common(occurring in more than 1 in 10 patients):

• Frequent infections, fever, sore throat, unexpected bruising, and bleeding (blood disorders such as low red blood cell count, low white blood cell count, low platelet count, and low granulocyte count. However, blood test results may return to normal after each treatment cycle)
• Common(occurring in less than 1 in 10 patients):
• Swelling and redness of the vein
• Uncommon(occurring in less than 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
• Swelling of limb tissues
• Unknown:
• Allergic reactions, including itching, rash, swelling of the face and/or 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, the patient should immediately inform their doctor or go to the emergency room.

Other side effects include:

Very common(occurring in more than 1 in 10 patients):

• Hair loss
• Vomiting, mouth ulcers, nausea
• Weakness
• Common(occurring in less than 1 in 10 patients):
• Diarrhea, abdominal pain, constipation, feeling of fullness in the stomach, and loss of appetite
• Impaired 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 darkening
• 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
• Mild increase in body temperature, chest pain, increased heart rate, shortness of breath or gasping
• Abnormal liver function test results
• Uncommon(occurring in less than 1 in 100 patients):
• Increased white blood cell count
• Dizziness, ear infections
• Bleeding, sensitivity, or enlargement of the gums, thrush
• Thirst
• Redness, excessive heat, and tenderness due to inflammation of the subcutaneous tissue

Reporting side effects

If any side effects occur, including those not listed in the leaflet, the patient should inform their doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products Al. Jerozolimskie 181C, 02-222 Warsaw Tel.: +48 22 49 21 301 Fax: +48 22 49 21 309 e-mail: [email protected] Side effects can also be reported to the marketing authorization holder. By reporting side effects, more information can be gathered on the safety of the medicine.

5. How to store Cyrdanax

The medicine should be stored out of sight and reach of children. Do not use this medicine after the expiry date stated on the vial and carton. The expiry date refers to the last day of the month. Before opening the vial:

• Do not store above 30°C.
• Store in the original packaging to protect from light.
• After dissolving the medicine and diluting: The solution should be used immediately. If not used immediately, the user is responsible for storage and storage time - do not store for more than 4 hours at a temperature between 2°C and 8°C (in the refrigerator) without light.

6. Contents of the packaging and other information

What Cyrdanax contains

The active substance of the medicine is dexrazoxane (in the form of hydrochloride). 1 ml of the prepared solution contains 20 mg of dexrazoxane (in the form of hydrochloride) Vial 250 mg: Each vial contains 250 mg of dexrazoxane (in the form of hydrochloride) to prepare a solution in 12.5 ml of water for injections. Vial 500 mg: Each vial contains 500 mg of dexrazoxane (in the form of hydrochloride) to prepare a solution in 25 ml of water for injections. The medicine does not contain other ingredients.

What Cyrdanax looks like and what the packaging contains:

This medicine is a white or almost white powder for solution for infusion. It is available in packs of 1 or 4 vials of brown glass containing 250 mg or 500 mg of dexrazoxane. Not all pack sizes may be marketed.

Marketing authorization holder

Pharmaselect International Beteiligungs GmbH Ernst-Melchior-Gasse 20 1020 Vienna, Austria

Manufacturer

BAG Health Care GmbH Amtsgerichtsstrasse 1-5, 35423 Lich, Germany

This medicine is authorized in the Member States of the European Economic Area under the following names:

Austria, Czech Republic, France, Germany, Hungary, Poland, Romania, Slovakia: Cyrdanax Date of last revision of the leaflet:November 2018

The following information is intended for healthcare professionals only

Preparation of the solution for intravenous infusion

Dissolution:The contents of each 500 mg vial should be dissolved in 25 ml of water for injections. The contents of the vial dissolve within a few minutes with gentle shaking. The resulting solution has a pH of approximately 1.8. The solution should be diluted before administration to the patient. The contents of each 250 mg vial should be dissolved in 12.5 ml of water for injections. The contents of the vial dissolve within a few minutes with gentle shaking. The resulting solution has a pH of approximately 1.8. The solution should be diluted before administration to the patient. Dilution:To avoid the risk of thrombophlebitis at the injection site, Cyrdanax should be diluted before infusion with one of the fluids listed in the table below. It is recommended to use solutions with a higher pH. The final volume of the fluid is proportional to the number of vials of Cyrdanax used and the volume of fluid used for dilution, which is from 12.5 ml to 100 ml per vial. The following table summarizes the final volume and approximate pH of the dissolved and diluted Cyrdanax for one and four vials. The minimum and maximum volume of infusion fluids used per vial is listed below.

Vials 500 mg:

Vials 250 mg:

Infusion fluid used for dilution

Volume of fluid used for dilution of 1 vial of dissolved Cyrdanax

Final volume of 1 vial

Final volume of 4 vials

pH(approximate)Ringer's solution with lactate 12.5 ml 25 ml 100 ml 2.4 50 ml 62.5 ml 250 ml 3.5 0.16 M sodium lactate* 12.5 ml 25 ml 100 ml 3.9 50 ml 62.5 ml 250 ml 4.6 To increase the pH of the solution, it is usually recommended to use a larger volume of diluent (up to 100 ml of additional diluent per 12.5 ml of dissolved Cyrdanax). If necessary and required by the patient's hemodynamic status, smaller volumes of diluent can be used (minimum 12.5 ml of additional diluent per 12.5 ml of dissolved Cyrdanax). * Sodium lactate 11.2% should be diluted 1:6 to achieve a concentration of 0.16 M Medicines intended for parenteral administration should be visually inspectedfor particulate matter. The solution of Cyrdanax immediately after dissolution has a color from colorless to yellow, but over time, changes in color may occur, which do not indicate a loss of activity of the medicine if it has been properly stored. However, if the medicine has a color other than colorless to yellow after dissolution, it should be discarded. Dosage:Cyrdanax is administered in a short intravenous infusion (15-minute), about 30 minutes before the administration of anthracyclines, in a dose 10 times higher than the dose of doxorubicin and 10 times higher than the dose of epirubicin. It is recommended to administer Cyrdanax in a dose of 500 mg/m², while the commonly used dosing regimen of doxorubicin is 50 mg/m² or 60 mg/m² in the commonly used dosing regimen of epirubicin. Children and adolescents:the safety and efficacy of the medicinal product Cyrdanax have not been established in children aged from 0 to 18 years. The medicinal product Cyrdanax is contraindicated in children aged from 0 to 18 years, in whom the planned dose of cumulative doxorubicin is less than 300 mg/m² or equivalent cumulative dose of another anthracycline. Renal impairment:in patients with moderate to severe renal impairment (creatinine clearance <40 ml min), the dose of dexrazoxane should be reduced by 50%. Hepatic impairment:the dose ratios should be maintained, e.g., if the dose of anthracycline is reduced, the dose of dexrazoxane should be reduced accordingly. Elderly patients (over 65 years of age):the dose can be adjusted in the case of treatment with Cyrdanax, depending on the patient's health status (in case of heart, liver, or kidney problems). Overdose:symptoms of overdose are leukopenia, thrombocytopenia, nausea, vomiting, diarrhea, skin reactions, and hair loss. There is no specific antidote, and treatment should be symptomatic. Treatment should include prevention and treatment of infections, fluid replacement, and nutritional support. Incompatibilities:dexrazoxane may increase the hematologic toxicity caused by chemotherapy or radiation therapy, and therefore, close monitoring of hematologic parameters is necessary during the first two cycles of treatment. Studies of interactions with dexrazoxane are limited. The effect on CYP450 enzymes or drug transporters has not been studied. Cyrdanax should not be mixed in one infusion with other medicines.

Storage instructions

Before opening the vial: Do not store above 30°C. Store in the original packaging to protect from light. After dissolving the medicine and diluting: Chemical and physical stability is maintained at 4°C for 8 hours. From a microbiological point of view, the medicine should be used immediately. If not used immediately, the user is responsible for storage and storage time - do not store for more than 4 hours at a temperature between 2°C and 8°C (in the refrigerator) without light.