Busulfan Fresenius Kabi 6 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Busulfan Fresenius Kabi 6 mg/ml concentrate for solution for infusion

busulfan

Read the entire leaflet carefully before you start using this medicine, because 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.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents:

1. What Busulfan Fresenius Kabi is and what it is used for
2. What you need to know before using Busulfan Fresenius Kabi
3. How to use Busulfan Fresenius Kabi
4. Possible side effects
5. How to store Busulfan Fresenius Kabi
6. Contents of the pack and other information

1. What Busulfan Fresenius Kabi is and what it is used for

This medicine contains the active substance busulfan, which belongs to a group of medicines called alkylating agents. Busulfan Fresenius Kabi destroys the original bone marrow prior to transplantation.

Busulfan Fresenius Kabi is used in adults, newborns, children and adolescents as a conditioning treatment prior to transplantation.

In adults, Busulfan Fresenius Kabi is used in combination with cyclophosphamide or fludarabine.

In newborns, children and adolescents, the medicine is used in combination with cyclophosphamide or melphalan.

This medicine will be administered to prepare you before receiving a bone marrow or hematopoietic progenitor cell transplant.

2. What you need to know before using Busulfan Fresenius Kabi

Do not use Busulfan Fresenius Kabi:

• 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 might be pregnant.

Warnings and precautions

Busulfan Fresenius Kabi 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, strict monitoring is required.

There is a possibility that the use of Busulfan Fresenius Kabi may increase the risk of developing another malignant tumour in the future. You must inform your doctor:

• if you have a history of liver, kidney, heart or lung disease,
• if you have a history of seizures,
• if you are taking any other medicines.

Blood clots may form in small blood vessels after haematopoietic cell transplantation (HCT) with high-dose treatment regimens including Busulfan Fresenius Kabi in combination with other medicines.

Use of Busulfan Fresenius Kabi with other medicines

Inform your doctor or pharmacist if you are taking, or have recently taken, any other medicines, including those obtained without a prescription. Busulfan Fresenius Kabi may interact with other medicines.

You should take special care if you are using itraconazole and metronidazole (used to treat certain types of infections) or ketobemidone (used to treat pain) or deferasirox (a medicine used to remove excess iron from the body), as this may increase the occurrence of adverse effects.

The use of paracetamol during the 72 hours prior to or during administration of Busulfan Fresenius Kabi should be done with caution.

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant or plan to become pregnant, consult your doctor before receiving treatment with Busulfan Fresenius Kabi. Women must not be pregnant during treatment with Busulfan Fresenius Kabi or within 6 months after completion of treatment.

Women must stop breastfeeding before starting treatment with Busulfan Fresenius Kabi.

Effective contraceptive methods should be used when either partner is receiving treatment with Busulfan Fresenius Kabi.

You may become infertile after treatment with Busulfan Fresenius Kabi. If you wish to have children, you should consult your doctor before treatment. Busulfan Fresenius Kabi may cause symptoms of menopause and in prepubescent girls may prevent the onset of puberty.

Men treated with Busulfan Fresenius Kabi are advised not to father children during treatment and for at least 6 months after completion of treatment.

3. How to use Busulfan Fresenius Kabi Dosage and administration:

Dosage and administration:

The dose of busulfan will be calculated according to your body weight.

In adults:

Busulfan Fresenius Kabi in combination with cyclophosphamide:

• The recommended dose of Busulfan Fresenius Kabi is 0.8 mg/kg.
• Each infusion will last 2 hours.
• Busulfan will be administered every 6 hours for 4 consecutive days prior to transplantation.

Busulfan Fresenius Kabi in combination with fludarabine:

• The recommended dose of busulfan is 3.2 mg/kg.
• Each infusion will last 3 hours.
• Busulfan Fresenius Kabi will be administered once daily for 2 or 3 consecutive days prior to transplantation.

In newborns, children and adolescents (from 0 to 17 years of age):

The recommended dose of Busulfan Fresenius Kabi in combination with cyclophosphamide or melphalan depends on body weight and ranges between 0.8 and 1.2 mg/kg.

Medications prior to administration of Busulfan Fresenius Kabi:

Before receiving Busulfan Fresenius Kabi, you will be treated with:

• anticonvulsant medications to prevent seizures (phenytoin or benzodiazepines), and
• antiemetic medications 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 treatment or the transplant procedure may include a decrease in circulating blood cell counts (an effect intended by the medicine to prepare you for transplant), infections, liver disorders such as blockage of a liver vein, graft-versus-host disease (where the graft reacts against your body), and pulmonary complications. Contact your doctor or nurse immediately if you experience any of the following symptoms. 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):

Blood: decreased number of circulating blood cells (red and white cells), and platelets. Infections. Nervous system: insomnia, anxiety, dizziness, and depression. Nutrition: loss of appetite, decreased levels of magnesium, calcium, potassium, phosphate, and albumin in the blood, and increased blood sugar levels. Cardiac: increased heart rate, increased or decreased blood pressure, vasodilation (widening of blood vessels), blood clot formation. Respiratory: difficulty breathing, nasal discharge (rhinitis), sore throat, cough, hiccups, nosebleeds, abnormal breathing sounds. Gastrointestinal: nausea, inflammation of the mucosa of the mouth, vomiting, abdominal pain, diarrhea, constipation, heartburn, anal discomfort, fluid in the abdomen. Hepatic: enlarged liver, jaundice, blockage of a liver vein. Skin: rash, itching, hair loss.

Musculoskeletal: back pain, muscle and joint pain. Renal: increased creatinine excretion, discomfort when urinating, decreased urine output, and blood in urine. General: fever, headache, weakness, chills, pain, allergic reactions, edema, pain or inflammation at the injection site, chest pain, inflammation of the mucosa.

Investigations: elevated liver enzyme levels and weight gain.

Common (may affect up to 1 in 10 people):

Nervous system: confusion, nervous system disorders. Nutrition: low blood sodium levels. Cardiac: changes and abnormalities in heart rhythm, fluid retention or swelling around the heart, decreased ejection fraction. Respiratory: increased respiratory rate, respiratory failure, alveolar hemorrhage, asthma, collapse of small areas of the lung, fluid around the lung. Gastrointestinal: inflammation of the esophageal mucosa, intestinal paralysis, vomiting of blood. Skin: skin color disorders, skin redness, skin peeling. Renal: increased levels of nitrogenous components in the blood, moderate kidney failure, kidney disorders.

Rare (may affect up to 1 in 100 people):

Nervous system: delirium, restlessness, hallucinations, agitation, abnormal brain function, cerebral hemorrhage, and seizures. Cardiac: blood clots in the femoral artery, extra heartbeats, decreased heart rate, diffuse leakage of fluid from capillaries (small blood vessels). Respiratory: decreased oxygen levels in the blood. Gastrointestinal: bleeding from the stomach and/or intestine.

Frequency not known (cannot be estimated from available data)

Dysfunction of the sex glands.

Ocular disorders including clouding of the eye lens (cataract) and blurred vision (corneal thinning).

Menopausal symptoms and female infertility.

Brain abscesses. Skin inflammation, systemic infection. Liver disorders.

Increased blood lactate dehydrogenase. Increased blood 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, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Annex V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Busulfan Fresenius Kabi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the vial label and the outer carton after EXP.

Unopened vial:

Store in a refrigerator (2°C–8°C).

After dilution:

Chemical and physical in-use stability has been demonstrated for 8 hours (including infusion time) after dilution in 5% glucose injection solution or 9 mg/ml (0.9%) sodium chloride injection solution, when stored at 25°C ± 2°C, or for 12 hours when stored at 2°C–8°C followed by 3 hours at 25°C ± 2°C (including infusion time). Do not freeze.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and their containers once they are no longer needed. This will help protect the environment.

6. Package contents and other information

Composition of Busulfan Fresenius Kabi

• The active substance is busulfan. One ml of concentrate contains 6 mg of busulfan (60 mg in 10 ml vial) and (240 mg in 40 ml vial). After reconstitution: one ml of solution contains approximately 0.5 mg of busulfan.
• The other components are dimethylacetamide and macrogol 400.

Appearance of the medicinal product and contents of the container

This medicine is a concentrate for solution for infusion. When diluted, Busulfan Fresenius Kabi is a clear, colourless, viscous solution.

Busulfan Fresenius Kabi is supplied in clear glass vials. Each vial is wrapped in a plastic shrink film.

Each vial contains either 10 ml or 40 ml of concentrate.

A pack contains either 8 vials of 10 ml each or one 40 ml vial.

Marketing Authorisation Holder

Fresenius Kabi Deutschland GmbH
Else-Kröner-Straße 1,
61352 Bad Homburg v.d.Höhe
Germany

Manufacturer

Fresenius Kabi Deutschland GmbH
Pfingstweide 53
61169 Friedberg
Germany

Further information on this medicinal product is available upon request to the Marketing Authorisation Holder.

Date of latest revision of this leaflet: 05/2025

Other sources of information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

This information is intended for healthcare professionals only:

PREPARATION GUIDE

Busulfan Fresenius Kabi 6 mg/ml concentrate for solution for infusion

Busulfan

Read this guide before preparing and administering busulfan.

1. PRESENTATION

Busulfan is presented as a clear, colourless, viscous solution in 10 ml and 40 ml clear Type I glass vials. Busulfan must be diluted before administration.

2. 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 performed in a vertical laminar flow safety cabinet.

As with other cytotoxic compounds, caution should be exercised when handling or preparing busulfan solution:

• It is recommended to wear gloves and protective clothing.
• If the medicinal product, busulfan or a solution thereof, comes into contact with skin or mucous membranes, wash the affected area immediately and thoroughly with water.

After multiple needle insertions and withdrawal of the product, the 40 ml vials maintain microbial, chemical, and physical stability for up to 28 days at 5°C ± 3°C. Other storage times and conditions during use are the responsibility of the user.

Calculation of the amount of busulfan to be diluted and of diluent

Before using the medicinal product busulfan, it must be diluted with 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.

The volume of diluent must be equal to 10 times the volume of the concentrate, ensuring a final busulfan concentration of approximately 0.5 mg/ml.

The amount of concentrate and diluent for administration is calculated as follows for a patient with a body weight of Y kg:

• Amount of busulfan:

Y (kg) x D (mg/kg)
= A ml of busulfan to be diluted
6 (mg/ml)

Y: patient’s body weight in kg
D: busulfan dose (see section 4.2.)

• Amount of diluent:

(A ml of busulfan) x (10) = B ml of diluent

To prepare the final infusion solution, add (A) ml of busulfan 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 must be prepared by healthcare professionals using sterile transfer techniques.

• Use a syringe that is not made of polycarbonate, equipped with a needle:

• withdraw the calculated volume of concentrate from the vial.

• transfer the contents of the syringe into an infusion bag (or syringe) already containing the calculated amount of selected diluent. Always add busulfan to the diluent, not the reverse. Do not add busulfan to an infusion bag that does not contain 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.

• The diluted solution should be gently mixed by several inversions.

After dilution, 1 ml of infusion solution contains 0.5 mg of busulfan.

The diluted concentrate 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 injection solution.

Residual medicine should 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 should be administered over 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 medicinal product solution prior to busulfan infusion, and flush afterwards with 9 mg/ml (0.9%) sodium chloride injection solution or 5% glucose injection solution.

Busulfan must not be infused concomitantly with another intravenous solution.

Due to incompatibility, infusion components containing polycarbonate must not be used with busulfan.

For single use only. Only clear, particle-free solutions should be used.

Storage conditions

Unopened vials:
Store in a refrigerator (2°C–8°C).

Diluted solution:
Chemical and physical in-use stability has been demonstrated after dilution with 5% glucose injection solution or 9 mg/ml (0.9%) sodium chloride injection solution for 8 hours (including infusion time) when stored at 25°C ± 2°C, or for 12 hours when stored at 2°C–8°C followed by 3 hours at 25°C ± 2°C (including infusion time).

From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the storage times and conditions during use are the responsibility of the user and normally should not exceed the times mentioned above, even if dilution was carried out under controlled and validated aseptic conditions.

Do not freeze the diluted solution.

It is recommended that healthcare professionals and end users follow best practices, such as piercing the stopper perpendicularly and within the target ring to avoid hitting the stopper legs, using appropriate piercing speeds, and limiting needle reuse, to help reduce the risk of stopper coring and fragmentation.

3. PROCEDURE FOR PROPER DISPOSAL

Disposal of unused medicinal product 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.