Label: information for the user

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

busulfan

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

This medication contains the active ingredient busulfan, which belongs to a group of medicines called alkylating agents. Busulfan destroys the original bone marrow before transplantation.

Busulfano Fresenius Kabi is used in adults, newborns, children, and adolescentsas a pre-transplant treatment.

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

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

This medication will be administered to prepare you before receiving a bone marrow or hematopoietic stem cell transplant

Do not use Busulfano Fresenius Kabi:

• if you are allergic to busulfan or any of the other ingredients in this medicine (listed in section 6),
• if you are pregnant or think you may be pregnant.

Warnings and precautions

Busulfano Fresenius Kabi is a powerful cytotoxic medicine that causes a significant decrease in blood cells. At the recommended dose, this is the desired effect. For this reason, strict control should be carried out.

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

• if you have a previous history of liver, kidney, heart, or lung diseases,
• if you have a history of convulsive attacks,
• if you are taking other medicines.

Thrombosis may form in small blood vessels after hematopoietic stem cell transplantation (HSCT) with high doses of your treatment in combination with other medicines.

Use of Busulfano Fresenius Kabi with other medicines

Inform your doctor or pharmacist if you are using, have used recently other medicines, even those obtained without a prescription. Busulfano Fresenius Kabi may interact with other medicines.

You should be especially cautious if you are using itraconazole and metronidazole (used in the treatment of certain types of infections) or cetobemidone (used in the treatment of pain) or deferasirox (a medicine used to remove excess iron from the body), as it may increase the appearance of adverse effects.

The use of paracetamol during the 72 hours before or during the administration of Busulfano Fresenius Kabi should be carried out 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 Busulfano Fresenius Kabi. Women should not be pregnant during treatment with Busulfano Fresenius Kabi or in the 6 months following its completion.

Women should interrupt breastfeeding before starting treatment with Busulfano Fresenius Kabi.

Effective contraceptive methods should be used when one of the partners is being treated with Busulfano Fresenius Kabi.

It may not be possible to become pregnant (infertility) after treatment with Busulfano Fresenius Kabi. If you wish to have children, you should consult with your doctor before treatment. Busulfano Fresenius Kabi may produce menopausal symptoms and in preadolescent girls may prevent the onset of puberty.

It is recommended that men treated with Busulfano Fresenius Kabi not father children during and up to 6 months after completing treatment.

Dosage and administration:

The dosage of busulfan will be calculated based on your body weight.

In adults:

Busulfano Fresenius Kabi in combination with cyclophosphamide:

• The recommended dosage of Busulfano Fresenius Kabi is 0.8 mg/kg.
• Each infusion will last 2 hours
• Busulfano Fresenius Kabi will be administered every 6 hours for 4 consecutive days before the transplant.

Busulfano Fresenius Kabi in combination with fludarabine:

• The recommended dosage of Busulfano Fresenius Kabi is 3.2 mg/kg
• Each infusion will last 3 hours
• Busulfano Fresenius Kabi will be administered once a day for 2 or 3 consecutive days before the transplant.

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

The recommended dosage of Busulfano Fresenius Kabi in combination with cyclophosphamide or melphalan depends on your body weight, and varies between 0.8 and 1.2 mg/kg.

Medications prior to the administration of Busulfano Fresenius Kabi:

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

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Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Severe side effects

The most severe side effects associated with treatment with Busulfano Fresenius Kabi or the transplant procedure may include a decrease in circulating blood cell count (an effect intended by the medication to prepare you for the transplant), infections, liver disorders such as bile duct obstruction, graft-versus-host disease (the transplant reacts against your body), and respiratory 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 treat these side effects.

Other side effects may include:

Very common (may affect more than 1 in 10 people):

Blood:decrease in the number of circulating red and white blood cells, and platelets.Infections.Nervous system:insomnia, anxiety, dizziness, and depression.Nutrition:loss of appetite, decrease in magnesium, calcium, potassium, phosphate, and albumin levels in the blood, and increase in blood sugar levels.Cardiac:increase in heart rate, increase or decrease in blood pressure, vasodilation (increase in blood vessel diameter), and blood clot formation.Respiratory:difficulty breathing, nasal secretion (rhinitis), sore throat, cough, hiccups, nasal bleeding, and abnormal breathing sounds.Gastrointestinal:nausea, inflammation of the oral mucosa, vomiting, abdominal pain, diarrhea, constipation, chest burning, anal discomfort, and fluid in the abdomen.Hepatic:liver enlargement, jaundice, bile duct obstruction.Skin:eruption, itching, hair loss.

Musculoskeletal and skeletal:back pain, muscle and joint pain.Renal:increased creatinine excretion, urinary discomfort, and decreased urine production and hematuria.General:fever, headache, weakness, chills, pain, allergic reactions, edema, general pain or inflammation at the injection site, chest pain, mucosal inflammation.

Complementary examinations:high levels of liver enzymes and weight gain.

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

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

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

Nervous system:delirium, nervousness, hallucinations, agitation, abnormal brain function, cerebral hemorrhage, and convulsions.Cardiac:femoral artery thrombosis, additional heartbeats, decreased heart rate, diffuse capillary fluid leakage.Respiratory:decreased oxygen levels in the blood.Gastrointestinal:gastric and/or intestinal bleeding.

Unknown frequency (cannot be estimated from available data)

Sexual gland dysfunction.

Eye disorders including lens opacity (cataract) and blurred vision (corneal thinning).

Menopausal symptoms and female infertility.

Cerebral abscesses. Generalized skin inflammation. Liver disorders.

Increased lactate dehydrogenase in the blood. Increased uric acid and urea in the blood..

Incomplete dental development

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in Annex V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the vial label and on the box after CAD.

Sealed vial:

Store in refrigerator (2°C-8°C).

Diluted solution:

Chemical and physical stability has been confirmed for 8 hours (including infusion time) when stored at 25°C ± 2°C after dilution with a 5% glucose injectable solution or 0.9% sodium chloride solution, and for 12 hours after dilution when the solution is stored between 2°C and 8°C, plus an additional 3 hours at 25°C ± 2°C (including infusion time). Do not freeze.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medication that you no longer need. This will help protect the environment.

Composition of Busulfan Fresenius Kabi

• The active ingredient is busulfan. One ml of the concentrate contains 6 mg of busulfan (60 mg in the vial). After dissolution: one ml of the solution contains approximately 0.5 mg of busulfan.
• The other components are dimethylacetamide and macrogol 400.

Appearance of the product and contents of the package

This medication is a concentrate for solution for infusion. When diluted, Busulfan Fresenius Kabi is a clear, colorless, and viscous solution.

Busulfan Fresenius Kabi is supplied in transparent glass vials. Each vial contains 60 mg of busulfan. Each vial is wrapped with a retractable plastic film.

Each vial contains 10 ml of concentrate.

Package size

Package containing 8 vials (8 cartons of 1 vial).

Marketing authorization holder

Fresenius Kabi Deutschland GmbH

Else-Kröner-Straße 1,

61352 Bad Homburg v.d.Höhe

Germany

Responsible manufacturer

Fresenius Kabi Deutschland GmbH

Pfingstweide 53

61169 Friedberg

Germany

For more information about this medication, please contact the marketing authorization holder.

Last review date of this leaflet: {MM/YYYY}

Other sources of information

The detailed information about this medication is available on the website of the European Medicines Agency http://www.ema.europa.eu .

This information is intended solely for healthcare professionals: PREPARATION GUIDE

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

Busulfan

Read this guide before preparing and administering Busulfan Fresenius Kabi.

1. Presentation

Busulfan Fresenius Kabi is presented as a clear, colorless, and viscous solution in transparent glass vials of type I, 10 ml.

Busulfan Fresenius Kabi must be diluted before administration.

1. RECOMMENDATIONS FOR SAFE HANDLING

Proper handling and disposal procedures for anticancer medications must be taken into account.

All transfer procedures require strict adherence to aseptic techniques; preferably, a laminar flow hood with vertical airflow should be used.

As with other cytotoxic compounds, caution should be exercised when handling or preparing the Busulfan Fresenius Kabi solution:

• It is recommended to use gloves and protective clothing.
• If the medication, Busulfan Fresenius Kabi or a solution of the same, comes into contact with the skin or mucous membranes, immediately and abundantly wash the area with water.

CALCULATION OF THE AMOUNT OF BUSULFAN FRESENIUS KABI AND DILUENT FOR THE SOLUTION

Before using the Busulfan Fresenius Kabi medication, it is necessary to dilute the product with sodium chloride 9 mg/ml (0.9%) injection solution or with 5% glucose injection solution.

The amount of diluent must be equal to 10 times the volume of Busulfan Fresenius Kabi, which ensures that the final concentration of busulfan is approximately 0.5 mg/ml.

The amount of Busulfan Fresenius Kabi and diluent for administration will be calculated as follows for a patient with a body weight of Y kg:

• Amount of Busulfan Fresenius Kabi:

Y (kg) x D (mg/kg)

= A ml of Busulfan Fresenius Kabi to dilute

6 (mg/ml)

Y: patient's body weight in kg

D: Busulfan Fresenius Kabi dose (see Technical Data Sheet section 4.2)

• Amount of diluent:

(A ml of Busulfan Fresenius Kabi) x (10) = B ml of diluent

To prepare the final infusion solution, the (A) ml of Busulfan Fresenius Kabi are added to the (B) ml of diluent (sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution).

PREPARATION OF THE INFUSION SOLUTION

Busulfan Fresenius Kabi must be prepared by healthcare professionals using sterile transfer techniques.

• A syringe that is not made of polycarbonate, equipped with a needle, must be used:

• The diluted solution must be mixed carefully by several inversions.

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

The diluted solution of Busulfan Fresenius Kabi is a clear, colorless solution.

INSTRUCTIONS FOR USE

Before and after each infusion, the circuit of catheterization must be washed with 5 ml of sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

The residual medication must not be infused through the administration system, as the rapid injection of Busulfan Fresenius Kabi has not been studied and is not recommended.

The total dose of Busulfan Fresenius Kabi prescribed must be administered within a period of 2 or 3 hours, depending on the conditioning regimen.

Small volumes should be administered over 2 hours using an electronic syringe pump. In this case, it is recommended to use a perfusion device with a minimum dead space (e.g., 0.3-0.6 ml). Purgation with the medication solution before infusion of Busulfan Fresenius Kabi and subsequent washing with sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

Busulfan Fresenius Kabi must not be infused concomitantly with another intravenous solution.

Due to incompatibility, components of infusion that contain polycarbonate must not be used with busulfan.

Medication for single use only. Only transparent, particle-free solutions must be used.

CONSERVATION CONDITIONS

Sealed vials:

Store in the refrigerator (2°C-8°C).

Diluted solution:

It has been confirmed that the chemical and physical stability during use after dilution with 5% glucose injection solution or sodium chloride 9 mg/ml (0.9%) injection solution is 8 hours (including infusion time) at 25°C ±2°C or 12 hours after dilution if the solution is stored between 2°C-8°C plus 3 additional hours at 25°C ±2°C (including infusion time).

From a microbiological point of view, the product must be used immediately after dilution. If not used immediately, the times and conditions of conservation during use are the responsibility of the user and are normally not longer than those mentioned above, although the dilution has taken place in controlled and validated aseptic conditions.

Do not freeze the diluted solution.

1. PROCEDURE FOR ADEQUATE DISPOSAL

The disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations regarding the disposal of cytotoxic medications.