Bleomicina Accord

Leaflet accompanying the packaging: patient information

Bleomycin Accord, 15,000 IU, powder for solution for injection/infusion
Bleomycin sulfate

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.
• Ask your doctor, hospital pharmacist, or nurse if you have any questions.
• If you experience any side effects, including any possible side effects not listed in this leaflet, contact your doctor, hospital pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Bleomycin Accord and what is it used for

The active substance of Bleomycin Accord is bleomycin sulfate. Bleomycin Accord belongs to a group of cytostatic medicines, which are anticancer medicines, sometimes referred to as chemotherapeutics. These medicines attack cancer cells and prevent them from dividing. Bleomycin Accord is used to treat:

• certain types of tumors (squamous cell carcinoma) of the head and neck, cervix, and external genitalia,
• certain lymph node tumors (e.g., Hodgkin's disease and non-Hodgkin's lymphoma of medium and high malignancy),
• testicular cancer,
• fluid accumulation in the lungs caused by cancer.

Bleomycin Accord may be used as a single medicine or in combination with other anticancer medicines and/or in combination with radiotherapy.

2. Important information before using Bleomycin Accord

Do not use Bleomycin Accord:

• if the patient is allergic to bleomycin sulfate or another similar anticancer medicine,
• if the patient has ataxia-telangiectasia (a very rare inherited disease that causes coordination difficulties and infection risk),
• if the patient has acute lung infection or severe lung function disorders,
• if the patient has previously had lung damage that was probably caused by bleomycin,
• during breastfeeding (see "Pregnancy and breastfeeding").

Warnings and precautions

Before starting treatment with Bleomycin Accord, consult your doctor, pharmacist, or nurse:

• if the patient is over 60 years old,
• if the patient has kidney or liver function disorders,
• if the patient has or has had lung diseases in the past,
• if the patient has undergone lung radiotherapy before bleomycin treatment or is receiving radiotherapy during bleomycin treatment,
• if the patient has chickenpox,
• if the patient is taking oxygen. The doctor should be informed about the use of bleomycin. The doctor should also be informed if the patient is scheduled for surgery, as modification of bleomycin treatment may be necessary.

These patient groups are more sensitive to the harmful effects of bleomycin on the lungs. The patient will likely be examined more frequently by the doctor and/or undergo a lung X-ray. In patients treated with bleomycin, regular lung function tests should be performed to monitor the potential harmful effects of bleomycin on the lungs. If the patient experiences cough and/or shortness of breath, they should immediately inform their doctor, as this may indicate harmful effects of bleomycin on the lungs.

Bleomycin Accord and other medicines

Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or plan to take. Interactions occur when medicinal products used together affect each other's effectiveness and/or side effects. Interactions may occur when bleomycin is used with the following medicines:

• Carmustine, mitomycin, cyclophosphamide, gemcitabine (used to treat certain types of tumors) and methotrexate (used to treat certain types of tumors, rheumatoid arthritis, and severe skin diseases): there is an increased risk of harmful effects on the lungs.
• Cisplatin (anticancer medicine) and other medicines that cause kidney damage: there is an increased risk of bleomycin side effects (increased pulmonary toxicity).
• Vinca alkaloids (a group of medicines used to treat certain types of tumors, e.g., vincristine, vinblastine): circulatory disorders in the limbs (fingers and toes, tip of the nose) may occur. In very severe cases, these parts of the body may become gangrenous.
• Acetyldigoxin (a medicine used to treat heart rhythm disorders): there is a risk of reduced acetyldigoxin effectiveness.
• Phenytoin (a medicine used to treat epilepsy): there is a risk that phenytoin's effectiveness may be reduced.
• Clozapine (a medicine for schizophrenia): it may cause a significant decrease in white blood cell count, increasing the risk of infections.
• Radiation therapy: increased risk of side effects related to the lungs and/or mucous membranes.
• Oxygen: increased risk of pulmonary toxicity if oxygen is administered during anesthesia.
• Gentamicin, amikacin, and ticarcillin (medicines that inhibit bacterial growth): the effectiveness of these substances may be reduced.
• Cyclosporine and tacrolimus (medicines that reduce immune system activity): risk of excessive lymphocyte production.
• Granulocyte colony-stimulating factor: may cause increased lung damage.
• Live vaccines: there is a risk of severe or life-threatening infections caused by the vaccine. Patients receiving bleomycin should not be given live vaccines.

Pregnancy, breastfeeding, and fertility

Pregnancy
If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor or pharmacist before using this medicine.
Animal studies have shown that the medicine may harm the fetus.
Bleomycin should be avoided during pregnancy, especially during the first three months.
If bleomycin treatment is necessary during the first three months of pregnancy, a medical consultation regarding termination of pregnancy is necessary.
Both men and women must use effective contraception during bleomycin treatment and for six months after treatment. If pregnancy occurs during bleomycin treatment, genetic counseling is recommended.
Men who plan to have children in the future should consult about sperm storage before starting bleomycin treatment, as there is a risk of irreversible infertility caused by the treatment.
Breastfeeding
It is not known whether bleomycin or its metabolites pass into human milk, but because there is a possibility of harmful effects of bleomycin on the child, breastfeeding should not be done during treatment.
Fertility
The use of Bleomycin Accord may cause irreversible infertility.

Driving and using machines

This medicine may affect your reactions and ability to drive or operate machinery.
Side effects of chemotherapy with bleomycin, such as nausea and vomiting, may occur. If such side effects occur, do not drive or operate machinery that requires concentration.

Bleomycin Accord, powder for solution for injection/infusion contains sodium.

The medicine contains less than 1 mmol of sodium (23 mg) per dose, so the medicine is considered "sodium-free".

3. How to use Bleomycin Accord

Your doctor will determine the required dose based on the dosing information presented later in this leaflet.
Usually, the administered dose is:
Dose (total) depends on the therapeutic indication, age, kidney function, and combination with other anticancer medicines. The doctor will determine the dose of bleomycin, duration of treatment, and number of treatment days. These may vary depending on the patient.
There is a risk of severe hypersensitivity reaction, especially in patients with lymphoma diagnosis, which may occur immediately after administration or later. Therefore, the doctor will administer a test dose to the patient and observe them for 4 hours before starting bleomycin treatment for the first time.
Method of administration
The doctor may administer bleomycin: intravenously or intra-arterially, subcutaneously, intramuscularly, directly into the tumor, or into the space surrounding the lungs (intrapleurally) by injection or infusion.
Use in children and adolescents
There is insufficient data on the use of bleomycin in children and adolescents. Until more information is available, bleomycin should be used in this patient group only in exceptional circumstances and in specialized facilities.

Using a higher dose of Bleomycin Accord than recommended

Symptoms that may occur if the patient has received too high a dose of Bleomycin Accord include: low blood pressure, fever, rapid heart rate, and shock. If any of these symptoms occur, contact your doctor, who will prescribe appropriate treatment. Treatment should be stopped immediately.
Information for the doctor
Information on overdose treatment can be found at the end of this leaflet.

Missing a dose of Bleomycin Accord

If you miss a dose, contact your treating doctor to determine whether and when you should take the missed dose.

Stopping treatment with Bleomycin Accord

If you suddenly stop using Bleomycin Accord without consulting your doctor, previous symptoms may recur.
If you have any further questions about using this medicine, contact your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everybody gets them.
Bleomycin Accord may cause immediate and delayed side effects.
Fever on the day of injection is the earliest reaction. Loss of appetite, hair loss, chills, fatigue, pneumonia (interstitial pneumonia) - shortness of breath or cough, and oral mucositis may also occur. Occasionally, pain at the injection site and in the tumor area has been observed. Other occasional side effects include decreased blood pressure and local thrombophlebitis after intravenous administration.
Skin and mucous membrane changes are the most common side effects and are observed in up to 50% of treated patients. These include: redness, rash, itching, ulceration, stretch marks, and blisters, severe discoloration, tenderness, and swelling of the fingertips.

Severe side effects

You should immediately contact your doctor if you experience any of the following symptoms:

• cough
• shortness of breath
• crackling or bubbling sound while breathing

Treatment may need to be discontinued.
Other side effects include:
Very common(may affect more than 1 in 10 people)

• interstitial pneumonia (inflammatory changes in the lungs)
• pulmonary fibrosis (lung tissue disease caused by increased production of connective tissue between alveoli)
• breathing difficulties
• loss of appetite
• weight loss
• nausea and vomiting
• oral mucositis
• oral mucosal inflammation
• skin redness with an inflammatory character
• itching
• stretch marks
• blistering
• discoloration (increased production of pigment)
• tenderness and swelling of the fingertips
• hyperkeratosis (excessive thickening of the skin)
• hair loss

Common(may affect up to 1 in 10 people)

• severe hypersensitivity reactions. These reactions may occur immediately or after a few hours after the first or second dose. You should immediately contact your doctor if you suddenly experience wheezing, difficulty breathing, swelling of the eyelids, face, or lips, rash, or itching (especially if it affects the whole body). Idiosyncratic reactions (various types of hypersensitivity reactions).
• headache
• acute respiratory failure (acute respiratory distress syndrome, ARDS)
• respiratory failure
• pulmonary embolism
• rash, urticaria, erythema
• skin hardening
• edema (due to fluid retention in tissues)
• skin inflammatory reaction
• fever, chills, and malaise

Uncommon(may affect up to 1 in 100 people)

• bone marrow suppression (bone marrow damage)
• leukopenia (decreased white blood cell count)
• neutropenia (decreased granulocyte count in the blood)
• thrombocytopenia (decreased platelet count)
• bleeding (bleeding)
• dizziness
• disorientation
• low blood pressure
• angular stomatitis and diarrhea
• nail deformation and discoloration, blister formation at pressure points
• muscle and joint pain
• oliguria (decreased urine output)
• pain during urination
• polyuria (increased urine output)
• urinary retention
• tumor pain
• phlebitis
• thickening (thickening of tissue after intramuscular or local administration)

Rare(may affect up to 1 in 1,000 people)

• neutropenic fever (fever caused by decreased white blood cell count)
• myocardial infarction, pericarditis (inflammation of the fibrous sac surrounding the heart), and chest pain
• brain infection, microangiopathic hemolytic anemia (disease of small and medium-sized blood vessels and capillaries), hemolytic-uremic syndrome (severe blood and kidney disease)
• cerebral arteritis (inflammation of small and medium-sized arteries in the brain)
• Raynaud's phenomenon (vascular disorder), arterial thrombosis, deep vein thrombosis
• liver function disorders
• scleroderma (hardening of connective tissue)

Very rare(may affect up to 1 in 10,000 people)

• tumor lysis syndrome (disorder occurring after rapid breakdown of tumors)

Frequency not known(cannot be estimated from available data)

• sepsis (blood infection)
• significant decrease in blood cell count (pancytopenia)
• decrease in red blood cell count (anemia)

Reporting side effects

If you experience any side effects, including any possible side effects not listed in this leaflet, contact your doctor, hospital pharmacist, or nurse.
You can also report side effects directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products,
Jerozolimskie Avenue 181C
02-222 Warsaw
tel.: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.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 medicine.

5. How to store Bleomycin Accord

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after EXP.
The expiry date refers to the last day of the month stated.
Store in a refrigerator (2°C - 8°C).
After reconstitution and dilution, the chemical and physical stability of the medicine has been demonstrated for 10 days at 2°C - 8°C and for 48 hours at room temperature. From a microbiological point of view, the reconstituted/diluted medicinal product should be used immediately. If the product is not used immediately, the storage time and conditions before use are the responsibility of the user and should not exceed the storage times stated above.
For single use only. Dispose of any remaining solution.
Do not use Bleomycin Accord if you notice visible signs of product deterioration or damage to the vial and closure.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the packaging and other information

What Bleomycin Accord contains

The active substance is bleomycin (as bleomycin sulfate).
One vial contains 15,000 IU of bleomycin (as bleomycin sulfate).
The other ingredients are sodium hydroxide (to adjust pH), hydrochloric acid (to adjust pH).

What Bleomycin Accord looks like and contents of the pack

White or yellowish lyophilized substance in a clear glass (type I) vial closed with a bromobutyl rubber stopper and an aluminum flip-off seal.
The pack contains 1, 10, or 100 vials.
Not all pack sizes may be marketed.

Marketing authorization holder

Accord Healthcare Polska Sp. z o.o.
Taśmowa 7
02-677 Warsaw
Tel: +48 22 577 28 00

Manufacturer/Importer

Accord Healthcare B.V.
Winthontlaan 200, 3526KV Utrecht
Netherlands
Accord Healthcare Polska Sp.z.o.o.
Lutomierska 50,
95-200, Pabianice

This medicine is authorized in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:

Date of last revision of the leaflet: November 2024

The following information is intended for healthcare professionals only

Dosage and administration

Bleomycin is administered parenterally by intramuscular injection, intravenous injection/infusion, intra-arterial injection/infusion, subcutaneous injection, intratumoral injection, or intrapleural administration.

Dosage

Adults

• 1) Squamous cell carcinoma (squamous cell carcinoma) Intramuscular injection or intravenous injection 10-15 x 10 IU/m² body surface area (BSA), once or twice a week, at 3-4 week intervals, until a cumulative lifetime dose of 360 x 10 IU. Intravenous infusion 10-15 x 10 IU/m² BSA per day, for 6-24 hours, over 4 to 7 consecutive days, at 3-4 week intervals.
• 2) Hodgkin's disease and non-Hodgkin's lymphoma In monotherapy: intramuscular injection or intravenous injection 5-15 x 10 IU/m² BSA, once or twice a week, until a cumulative dose of 225 x 10 IU. Due to the possibility of a pseudo-anaphylactic reaction, patients with lymphoma should be treated with small doses (e.g., 2 x 10 IU) at the first two administrations. If no acute reactions occur after 4 hours of observation, the usual dosing schedule can be continued.
• 3) Testicular tumors Intramuscular injection or intravenous injection 10-15 x 10 IU/m² body surface area, once or twice a week, at 3-4 week intervals, until a cumulative dose of 400 x 10 IU. Intravenous infusion 10-15 x 10 IU/m² BSA per day, for 6-24 hours, over 5-6 consecutive days, at 3-4 week intervals.
• 4) Malignant pleural effusion 60 x 10 IU in 100 ml of physiological saline, intrapleurally, as a single dose, which may be repeated after 2-4 weeks, depending on the response. Since about 45% of bleomycin is absorbed, this should be taken into account when determining the cumulative dose (body surface area, kidney function, lung function).

The occurrence of stomatitis is the most helpful indicator of the patient's tolerance to the maximum dose. The cumulative dose should not exceed 400 x 10 IU (which corresponds to 225 x 10 IU/m² body surface area) in patients under 60 years of age, due to the increased risk of pulmonary toxicity in all indications. In patients with lymphoma, the cumulative dose should not exceed 225 x 10 IU.

Incompatibilities

Bleomycin should not be mixed with solutions of basic amino acids, riboflavin, ascorbic acid, dexamethasone, aminophylline, benzylpenicillin, carbenicillin, cephalothin, cefazolin, diazepam, furosemide, glutathione, hydrogen peroxide, sodium heparin, and thiols.

Renal impairment
In case of renal impairment, especially if creatinine clearance is less than 35 ml/min, bleomycin elimination is delayed. There are no specific guidelines for dose modification in these patients, but it is recommended that patients with moderate renal impairment (GFR 10-50 ml/min) receive 75% of the usual dose at the usual dose intervals, and patients with severe renal impairment (GFR less than 10 ml/min) receive 50% of the usual dose at the usual dose intervals. No dose modification is required in patients with GFR greater than 50 ml/min.
Combination therapy
When bleomycin is used in combination therapy, dose modification may be necessary. The dose of bleomycin should be reduced when the medicine is used in combination with radiotherapy, as the risk of mucosal damage is increased. Dose modification may also be required when bleomycin is used in combination chemotherapy. Detailed information on the regimens used in certain indications can be found in current literature.
Method of administration and preparation of the solution for injection:
N.B.: The entire contents of the vial (15,000 IU) should be dissolved in an appropriate amount of solvent to prepare the solution. Then, the required number of units is taken from this solution for treatment.

Special precautions for disposal and preparation of the medicinal product for administration

General guidelines for safe handling of cytotoxic medicinal products should be followed. Appropriate precautions should be taken to avoid contact with the skin, mucous membranes, and eyes. In case of contamination, the affected areas should be thoroughly washed with water.

Information on overdose

There is no specific antidote. Removal of bleomycin from the body by dialysis is practically impossible. Acute reaction to overdose includes hypotension, fever, tachycardia, and shock. Treatment is only symptomatic. In case of respiratory complications, the patient should be treated with corticosteroids and a broad-spectrum antibiotic. Usually, the pulmonary reaction to overdose (fibrosis) is irreversible, unless it is diagnosed at an early stage.