Busulfan Zentiva 6 mg/ml concentrate for infusion solution EFG
SpainTable of Contents
Patient Information Leaflet
Introduction
Patient Information Leaflet
Busulfan Zentiva 6 mg/ml concentrate for solution for infusion EFG
Read the entire leaflet carefully before you start using 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, ask your doctor, pharmacist, or nurse.
- If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.
Leaflet Contents
- What Busulfan Zentiva is and what it is used for
- What you need to know before using Busulfan Zentiva
- How to use Busulfan Zentiva
- Possible side effects
- How to store Busulfan Zentiva
- Contents of the pack and other information
1. What Busulfan Zentiva is and what it is used for
Busulfan Zentiva contains the active substance busulfan, which belongs to a group of medicines called alkylating agents. Busulfan Zentiva destroys the original bone marrow prior to transplantation.
Busulfan Zentiva is used in adults, newborns, children and adolescents as a preparative treatment prior to transplant.
In adults, Busulfan Zentiva is used in combination with cyclophosphamide or fludarabine.
In newborns, children and adolescents, Busulfan Zentiva is used in combination with cyclophosphamide or melphalan.
This medicine will be administered to prepare you before receiving a bone marrow transplant or hematopoietic progenitor cell transplant.
2. What you need to know before using Busulfan Zentiva
Do not use Busulfan Zentiva:
- if you are allergic to busulfan or to any of the other ingredients of this medicine (listed in section 6),
- if you are pregnant or think you may be pregnant.
Warnings and precautions
Busulfan Zentiva is a potent cytotoxic medicine that causes a significant decrease in blood cells. At the recommended dose, this is the intended effect. For this reason, close monitoring is required. The use of Busulfan Zentiva may increase the risk of developing another malignant tumour in the future. You must inform your doctor:
- if you have a problem with your liver, kidneys, heart or lungs,
- if you have a history of seizures,
- if you are currently taking any other medicines.
Blood clots may form in small blood vessels after haematopoietic cell transplantation (HCT) when high-dose treatment with Busulfan Zentiva is used in combination with other medicines.
Other medicines and Busulfan Zentiva
Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines, including those obtained without a prescription. Busulfan Zentiva may interact with other medicines.
In particular, inform your doctor or pharmacist if you are taking any of the following medicines:
- Deferasirox (a medicine used to remove excess iron from the body).
Use extra caution if you are taking itraconazole and metronidazole (used to treat certain types of infections) or cetobemidone (used to treat pain), as these may increase the occurrence of adverse effects.
The use of paracetamol within 72 hours before or during administration of Busulfan Zentiva should be done with caution.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving treatment with Busulfan Zentiva. Women must not be pregnant during treatment with Busulfan Zentiva or for 6 months after treatment ends.
Women must stop breastfeeding before starting treatment with Busulfan Zentiva.
Effective contraceptive methods must be used when either partner is being treated with Busulfan Zentiva.
You may be unable to conceive (infertility) after treatment with Busulfan Zentiva. If you wish to have children, you should discuss this with your doctor before starting treatment. Busulfan Zentiva may also cause symptoms of menopause and, in pre-adolescent girls, may prevent the onset of puberty.
Men treated with Busulfan Zentiva are advised not to father children during treatment and for at least 6 months after treatment ends.
3. How to use Busulfano Zentiva
Dosage and administration:
The dose of Busulfano Zentiva will be calculated based on your body weight.
In adults:
Busulfano Zentiva in combination with cyclophosphamide:
- The recommended dose of Busulfano Zentiva is 0.8 mg/kg
- Each infusion will last 2 hours
- Busulfano Zentiva will be administered every 6 hours for 4 consecutive days prior to transplant.
Busulfano Zentiva in combination with fludarabine:
- The recommended dose of Busulfano Zentiva is 3.2 mg/kg
- Each infusion will last 3 hours
- Busulfano Zentiva will be administered once daily for 2 or 3 consecutive days prior to transplant.
In newborns, children and adolescents (0 to 17 years):
The recommended dose of Busulfano Zentiva in combination with cyclophosphamide or melphalan depends on body weight and ranges between 0.8 and 1.2 mg/kg.
- Each infusion will last 2 hours.
- Busulfano Zentiva will be administered every 6 hours for 4 consecutive days prior to transplant.
Medications prior to administration of Busulfano Zentiva:
Before receiving Busulfano Zentiva, you will be treated with:
- anticonvulsant medicines to prevent seizures (fits) (phenytoin or benzodiazepines), and
- antiemetic medicines to prevent vomiting.
4. Possible adverse effects
Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Serious adverse effects
The most serious adverse effects associated with Busulfan Zentiva treatment or the transplant procedure may include a decrease in circulating blood cell counts (an effect intended with the medicine to prepare you for transplant engraftment), infections, liver disorders such as blockage of a liver vein, graft-versus-host disease (where the graft reacts against your body), and pulmonary complications. Your doctor will regularly monitor your blood counts and liver enzymes to detect and manage these effects.
Other adverse effects may include:
Very common (may affect more than 1 in 10 people):
- decrease in the number of circulating blood cells (red and white) and platelets,
- infections,
- insomnia, anxiety, dizziness, and depression,
- loss of appetite, decreased levels of magnesium, calcium, potassium, phosphate, and albumin in the blood, and increased blood sugar levels,
- increased heart rate, increased or decreased blood pressure, vasodilation (widening of blood vessels), blood clot formation,
- difficulty breathing, nasal discharge (rhinitis), sore throat, cough, hiccups, nosebleeds, abnormal breathing sounds,
- nausea, inflammation of the mucous lining of the mouth, vomiting, abdominal pain, diarrhea, constipation, chest burning, anal discomfort, fluid in the abdomen,
- enlarged liver, jaundice (yellowing of the skin or whites of the eyes), blockage of a liver vein,
- rash, itching, hair loss,
- back pain, muscle and jaw pain,
- increased excretion of a chemical waste product, creatinine, through the kidneys for filtration and elimination in urine (creatinine clearance), discomfort during urination, decreased urine output, and blood in the urine,
- fever, headache, weakness, chills, pain, allergic reactions, edema (fluid retention), pain or inflammation at the injection site, chest pain, mucosal inflammation,
- elevated liver enzyme levels and weight gain,
- intestinal paralysis.
Common (may affect up to 1 in 10 people):
- confusion, nervous system disorders,
- low levels of sodium (salt) in the blood,
- changes and abnormalities in heart rhythm, fluid retention or swelling around the heart, decreased amount of blood pumped by the heart into the circulatory system (cardiac output),
- increased respiratory rate, respiratory failure, bleeding from the air sacs in the lungs called alveoli (alveolar hemorrhage), asthma, collapse of small areas of the lung, fluid around the lung,
- inflammation of the mucous lining of the esophagus, intestinal paralysis (lack of intestinal movement), vomiting of blood,
- skin discoloration disorders, skin redness, skin peeling,
- increased levels of nitrogen-containing components in the blood, moderate kidney failure, kidney disorders.
Uncommon (may affect up to 1 in 100 people):
- delirium (severe confusion), restlessness, hallucinations (seeing things that are not real), agitation (anxiety or nervousness), abnormal brain function, cerebral hemorrhage, and seizures,
- blood clots in the thigh artery (femoral artery), extra heartbeats, decreased heart rate, widespread leakage of fluid from capillaries (small blood vessels),
- decreased levels of oxygen in the blood,
- bleeding from the stomach and/or intestines.
Frequency not known (cannot be estimated from available data):
- dysfunction of the sex glands,
- eye disorders including clouding of the eye's lens (cataract) and blurred vision (corneal thinning),
- menopausal symptoms and female infertility,
- brain abscesses, skin inflammation, systemic infection,
- liver disorders,
- increased blood levels of lactate dehydrogenase enzyme,
- increased blood levels of uric acid and urea,
- incomplete dental development,
- increased blood pressure in the blood vessels of the lungs (pulmonary hypertension).
Reporting of adverse effects
If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.
5. Storage of Busulfan Zentiva
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label of the vial after EXP. The expiry date refers to the last day of the month indicated.
Unopened vial:
Store in a refrigerator (2 °C - 8 °C).
Diluted solution:
Chemical and physical in-use stability after dilution with 5% glucose injection or 9 mg/ml (0.9%) sodium chloride injection has been demonstrated to be 8 hours (including infusion time) when stored at 20 °C ± 5 °C, or 6 hours after dilution in 9 mg/ml (0.9%) sodium chloride injection when the solution is stored between 2 °C and 8 °C, followed by an additional 3 hours of storage at 20 °C ± 5 °C (including infusion time).
Do not freeze.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.
6. Contents of the pack and other information
Composition of Busulfan Zentiva
- The active substance is busulfan. One ml of concentrate contains 6 mg of busulfan (60 mg of busulfan in the vial). After reconstitution: one ml of solution contains approximately 0.5 mg of busulfan.
- The other components are N,N-dimethylacetamide, macrogol 400 and anhydrous citric acid.
Appearance of the product and contents of the container
Busulfan Zentiva is a concentrate for solution for infusion supplied in clear glass vials. Each vial contains 60 mg of busulfan.
Busulfan Zentiva is available in single packs containing 1 vial or multiple packs containing 8 vials.
When diluted, Busulfan Zentiva yields a clear, colourless solution.
Vials with or without plastic shrink wrap and protective base (disc). The shrink wrap does not come into contact with the product and provides additional protection during transport. It also improves safe handling of the product by healthcare professionals.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Zentiva k.s.,
U kabelovny 130,
Prague 10 – Dolní Mecholupy,
102 37 Czech Republic
Manufacturer 1
SGS Pharma Magyarorszag Kft.
Derkovits Gyula Utca 53,
Budapest XIX, 1193,
Hungary
Tillomed Malta Limited
Malta Life Sciences Park,
LS2.01.06 Industrial Estate,
San Gwann, SGN 3000, Malta
Further information about this medicine can be requested from the local representative of the Marketing Authorisation Holder:
Zentiva Spain S.L.U.
Avenida de Europa, 19, Edificio 3, Planta 1.
28224 Pozuelo de Alarcón, Madrid
Spain
This medicine is authorised in the Member States of the European Economic Area and the United Kingdom (Northern Ireland) under the following names:
United Kingdom (Northern Ireland): Busulfan Tillomed 6mg/ml concentrate for Solution for Infusion
France: Busulfan Tillomed 6mg/ml solution à diluer pour perfusion
Italy: Busulfan Tillomed
Germany: Busulfan Tillomed 6mg/ml Konzentrat zur Herstellung einer Infusionslösung
Spain: Busulfano Zentiva 6mg/ml concentrado para solución para perfusión EFG
Poland: Busulfan Zentiva
Date of latest review of this leaflet: July 2025
Other sources of information
Detailed information on this medicine is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).
This information is intended for healthcare professionals only:
PREPARATION GUIDE
Busulfan Zentiva 6 mg/ml concentrate for solution for infusion EFG
Busulfan
Read this guide before preparing and administering Busulfan Zentiva.
- PRESENTATION
Busulfan Zentiva is presented as a clear, colourless solution in 10 ml clear type I glass vials.
Busulfan Zentiva must be diluted before administration.
- RECOMMENDATIONS FOR SAFE HANDLING
Appropriate procedures for handling and disposal of cytotoxic medicinal products must be observed.
All transfer procedures require strict adherence to aseptic techniques; preferably, a vertical laminar flow safety cabinet should be used.
As with other cytotoxic compounds, caution should be exercised when handling or preparing Busulfan Zentiva solution:
- It is advisable to wear protective gloves and clothing.
- If the product (Busulfan Zentiva or a solution thereof) comes into contact with skin or mucous membranes, wash the affected area immediately and thoroughly with water.
Calculation of the amount of Busulfan Zentiva and diluent for the solution
Before using Busulfan Zentiva, the product must be diluted with 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.
The volume of diluent must be 10 times the volume of Busulfan Zentiva, ensuring a final busulfan concentration of approximately 0.5 mg/ml.
The amount of Busulfan Zentiva and diluent for administration is calculated as follows:
For a patient with a body weight of Y kg:
- Amount of Busulfan Zentiva:
Y: patient's body weight (in kg)
D: dose of Busulfan Zentiva (see section 4.2)
- Amount of diluent:
To prepare the final infusion solution, add (A) ml of Busulfan Zentiva to (B) ml of diluent (9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution).
Preparation of the solution for infusion
Busulfan Zentiva must be prepared by healthcare professionals using sterile transfer techniques.
-
Use a syringe that is not made of polycarbonate, fitted with a needle:
-
Withdraw the calculated volume of Busulfan Zentiva from the vial.
-
Transfer the contents of the syringe into an infusion bag (or syringe) already containing the calculated volume of selected diluent. Always add Busulfan Zentiva to the diluent, not the reverse. Do not add Busulfan Zentiva to an empty infusion bag or to a bag not containing 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.
-
The diluted solution should be mixed gently by several inversions.
After dilution, 1 ml of infusion solution contains 0.5 mg of busulfan.
After dilution, Busulfan Zentiva is a clear, colourless solution.
Instructions for use
Before and after each infusion, flush the catheter line with approximately 5 ml of 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose solution.
Residual medication must not be infused through the administration system, as rapid injection of busulfan has not been studied and is not recommended.
The total prescribed dose of Busulfan Zentiva should be administered over a period of two or three hours, depending on the conditioning regimen.
Small volumes should be administered over 2 hours using an electronic syringe pump. In such cases, an infusion set with minimal dead space (e.g., 0.3–0.6 ml) is recommended. Prime the system with the medication solution prior to infusion of Busulfan Zentiva and flush afterwards with 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.
Do not administer any other intravenous solution concomitantly with this infusion.
Do not use polycarbonate syringes with Busulfan Zentiva.
Single-use product. Only clear, particle-free solutions should be used.
Storage conditions
Closed vials:
Store in a refrigerator (2°C – 8°C).
Diluted solution:
Chemical and physical in-use stability after dilution with 5% glucose or 9 mg/ml (0.9%) sodium chloride solution has been confirmed for 8 hours (including infusion time) when stored at 20°C ± 5°C, or for 6 hours after dilution in 9 mg/ml (0.9%) sodium chloride solution when stored between 2°C and 8°C plus an additional 3 hours at 20°C ± 5°C (including infusion time).
From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the responsibility for storage times and conditions prior to use lies with the user.
- PROCEDURE FOR PROPER DISPOSAL
Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations regarding the disposal of cytotoxic medicinal products.