Busulfan Accord

Package Leaflet: Information for the Patient

Busulfan Accord, 6 mg/ml, Concentrate for Solution for Infusion

Busulfan

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

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

Table of Contents of the Package Leaflet

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

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

Busulfan Accord contains the active substance busulfan, which belongs to a group of medicines called alkylating agents. Busulfan Accord destroys the original bone marrow before transplantation. Busulfan Accord is used in adults, newborns, children, and adolescents for treatment beforetransplantation.In adults, Busulfan Accord is used in combination with cyclophosphamide and fludarabine. In newborns, children, and adolescents, Busulfan Accord is used in combination with cyclophosphamide or melphalan. The medicine is administered before receiving a bone marrow or hematopoietic stem cell transplant.

2. Important information before using Busulfan Accord

When not to use Busulfan Accord

Warnings and precautions

Busulfan Accord is a strong cytotoxic medicine that causes a significant decrease in the number of blood cells. At the recommended dose, this is a desired effect. Therefore, the patient is under close observation. There is a possibility that the use of Busulfan Accord may increase the risk of developing another type of cancer in the future. Inform your doctor:

There have been cases of blood clots in small blood vessels after hematopoietic stem cell transplantation (HCT) after using high doses of Busulfan Accord in combination with other medicines.

Busulfan Accord and other medicines

Tell your doctor about all medicines you are currently taking or have recently taken, as well as medicines you plan to take, including those available without a prescription. In particular, inform your doctor or pharmacist if you are taking deferasirox (a medicine used to remove excess iron from the body). Busulfan Accord may interact with other medicines. Be careful when using itraconazole and metronidazole (used for certain types of infections) or ketobemidone (used for pain relief), as this may increase the risk of side effects. Be careful when using paracetamol within 72 hours before or at the same time as Busulfan Accord administration.

Pregnancy, breastfeeding, and fertility

In pregnancy and during breastfeeding, or if you think you may be pregnant, consult your doctor before using Busulfan Accord. Women must not become pregnant while using Busulfan Accord and for up to 6 months after its completion. Women must stop breastfeeding before starting Busulfan Accord treatment. If either partner is being treated with Busulfan Accord, appropriate contraceptive measures should be used. After Busulfan Accord therapy, it may not be possible to become pregnant (infertility). If the patient is considering having children, discuss this with your doctor before starting treatment. Busulfan Accord may also cause symptoms of menopause, and in girls before puberty, it may inhibit development. Men treated with Busulfan Accord are advised not to plan fatherhood during treatment and for up to 6 months after its completion.

3. How to use Busulfan Accord

Dose and administration

The dose of Busulfan Accord is calculated based on the patient's body weight. Adults Busulfan Accord in combination with cyclophosphamide

• The recommended dose of Busulfan Accord is 0.8 mg/kg body weight.
• Each infusion lasts 2 hours.
• Busulfan Accord is administered every 6 hours for 4 consecutive days before transplantation.

Busulfan Accord in combination with fludarabine

• The recommended dose of Busulfan Accord is 3.2 mg/kg body weight.
• Each infusion lasts 3 hours.
• Busulfan Accord is administered once a day for 2 or 3 consecutive days before transplantation.

Newborns, children, and adolescents (from 0 to 17 years old) The recommended dose of Busulfan Accord in combination with cyclophosphamide or melphalan is calculated based on body weight and ranges from 0.8 to 1.2 mg/kg body weight.

• Each infusion lasts 2 hours.
• Busulfan Accord is administered every 6 hours for 4 consecutive days before transplantation.

Medicines given before using Busulfan Accord

Before administering Busulfan Accord, the patient receives:

• anti-seizure medicines to prevent seizures (phenytoin or benzodiazepines) and
• anti-emetic medicines to prevent vomiting.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Severe side effects

The most severe side effects after using busulfan or transplantation may include: decreased number of circulating blood cells (intended effect of the medicine for transplantation preparation), infection, liver disorders, including blockage of liver veins, graft-versus-host disease (the transplant attacks the patient's body), and pulmonary complications. Your doctor will regularly check your blood morphology and liver enzyme test results to detect and treat these complications.

Other side effects may include:

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

Blood:decreased number of circulating blood cells (red and white) and platelets. Infections. Nervous system:insomnia, anxiety, dizziness, and depression. Nutrition:loss of appetite, decreased magnesium, calcium, potassium, phosphate, and albumin levels in the blood, and increased blood sugar levels. Heart:rapid heart rate, increased or decreased blood pressure, vasodilation (increased diameter of blood vessels), and thrombosis. Respiratory:shortness of breath, nasal discharge (rhinitis), sore throat, cough, hiccups, nosebleeds, abnormal breath sounds. Gastrointestinal:nausea, oral mucositis, vomiting, abdominal pain, diarrhea, constipation, heartburn, discomfort in the anal area, ascites. Liver:liver enlargement, jaundice. Skin:rash, itching, hair loss. Musculoskeletal:back pain, muscle and joint pain. Kidney:increased creatinine excretion, discomfort when urinating, decreased urine output, and hematuria. General:fever, headache, weakness, chills, pain, allergic reaction, swelling, generalized pain or inflammation at the injection site, chest pain, mucositis.

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

Nervous system:confusion, neurological disorders. Nutrition:low sodium levels in the blood. Heart:changes and arrhythmias, pericardial effusion or pericarditis, decreased cardiac output. Respiratory:increased respiratory rate, respiratory failure, pulmonary hemorrhage, asthma, atelectasis, pleural effusion. Gastrointestinal:esophagitis, intestinal paralysis, bloody vomiting. Skin:skin discoloration, skin redness, skin peeling. Kidney:increased nitrogen compounds in the blood, moderate kidney failure, kidney disorders.

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

Nervous system:hallucinations, nervousness, delusions, agitation, brain disorders, cerebral hemorrhage, and seizures. Heart:femoral artery thrombosis, extrasystoles, bradycardia, capillary leak syndrome (small blood vessels). Respiratory:decreased oxygen levels in the blood. Gastrointestinal:gastrointestinal bleeding.

Frequency not known (cannot be estimated from the available data):

Endocrine disorders. Lens disorders, including cataracts and corneal clouding. Increased blood pressure in the pulmonary blood vessels (pulmonary hypertension). Menopausal symptoms and infertility in women. Brain abscess, skin infection, generalized infection. Liver disorders. Increased lactate dehydrogenase activity in the blood. Increased uric acid and urea levels in the blood. Incomplete tooth development.

Reporting side effects

If you experience any side effects, including those not listed in the package leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, 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, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Busulfan Accord

Store the medicine out of sight and reach of children. Do not use this medicine after the expiry date stated on the vial label and carton after EXP. Unopened vials:Store in a refrigerator (2°C - 8°C). Do not freeze the solution after dilution. Diluted solution:Chemical and physical stability after dilution with glucose 5% or sodium chloride 0.9% solution for injection has been demonstrated for 4 hours (including infusion time) at 20°C - 25°C or 15 hours after dilution when stored at 2°C - 8°C, followed by 3 hours at 20°C - 25°C (including infusion time). From a microbiological point of view, the product should be used immediately. If not used immediately, the storage times and conditions before use are the responsibility of the user. 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 pack and other information

What Busulfan Accord contains

• The active substance is busulfan. One ml of concentrate contains 6 mg of busulfan (60 mg in a vial). After dilution, one ml of solution contains 0.5 mg of busulfan.
• The other ingredients are dimethylacetamide and macrogol 400.

What Busulfan Accord looks like and contents of the pack

Busulfan Accord is a concentrate for solution for infusion, which is available in colorless glass vials: each vial contains 60 mg of busulfan. Busulfan Accord is a clear, colorless solution without visible particles, available in packs containing 1 vial or 8 vials of 10 ml concentrate for solution for infusion. Not all pack sizes may be marketed.

Marketing authorization holder:

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

Manufacturer/Importer:

Accord Healthcare Polska Sp.z o.o., ul. Lutomierska 50, 95-200 Pabianice, Poland

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

Date of last revision of the package leaflet: June 2025

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The following information is intended for healthcare professionals only.

PREPARATION INSTRUCTIONS

Busulfan Accord, 6 mg/ml, Concentrate for Solution for Infusion

Read these instructions before preparing and administering Busulfan Accord.

1. DESCRIPTION

Busulfan Accord is available as a clear, colorless solution in clear glass vials (Type I) of 10 ml. Busulfan Accord must be diluted before administration.

2. RECOMMENDATIONS FOR SAFE HANDLING

Follow the procedures for the safe handling of cytotoxic medicines. All transfer procedures require strict adherence to aseptic techniques, preferably using a vertical laminar flow hood. As with other cytotoxic compounds, caution should be exercised when handling and using the busulfan solution:

• wear gloves and protective clothing,
• in case of contact with busulfan concentrate or diluted solution on the skin or mucous membranes, immediately rinse the area thoroughly with water.

Calculation of the amount of Busulfan Accord to be diluted and the amount of diluent The medicine must be diluted before administration using sodium chloride 0.9% solution for injection or glucose 5% solution for injection. The amount of diluent must be 10 times the volume of Busulfan Accord, so that the final concentration of busulfan is approximately 0.5 mg/ml. The amount of Busulfan Accord and diluent should be calculated as follows: For a patient with a body weight of Y kg:

• Amount of Busulfan Accord:

Y (kg) x D (mg/kg) = A ml of Busulfan Accord to be diluted 6 (mg/ml) Y: patient's body weight in kg D: busulfan dose (see SmPC, section 4.2)

• Amount of diluent:

(A ml of Busulfan Accord) x (10) = B ml of diluent To prepare the final infusion solution, add (A) ml of Busulfan Accord to (B) ml of diluent (sodium chloride 0.9% solution for injection or glucose 5% solution for injection).

Preparation of the infusion solution Busulfan Accord must be prepared by healthcare professionals using sterile equipment.

• Using a non-polymeric syringe with a needle:
• draw up the calculated volume of Busulfan Accord from the vial;
• inject the contents of the syringe into an infusion bag (or syringe) that already contains the calculated volume of the chosen diluent. Busulfan Accord should always be added to the diluent, and not the diluent to the medicine. Busulfan Accord must not be injected into an infusion bag that does not contain sodium chloride 0.9% solution for injection or glucose 5% solution for injection.
• The diluted solution should be carefully mixed by inverting several times.

After dilution, 1 ml of the infusion solution contains 0.5 mg of busulfan. After dilution, Busulfan Accord is a clear, colorless solution. Instructions for useBefore and after each infusion, the implanted venous catheter should be flushed with approximately 5 ml of sodium chloride 0.9% solution for injection or glucose 5% solution for injection. The medicine remaining in the lines must not be flushed, as rapid infusion of busulfan has not been studied and is not recommended. The entire prescribed dose of Busulfan Accord should be administered over 2 or 3 hours, depending on the conditioning regimen. Small volumes can be administered over 2 hours using an electric syringe. In this case, use infusion sets with a minimum priming volume before use (i.e., 0.3-0.6 ml), filled with the medicine solution before starting the infusion of Busulfan Accord, and then flushed with sodium chloride 0.9% solution for injection or glucose 5% solution for injection. Busulfan Accord must not be administered simultaneously with another intravenous solution. Polyethylene syringes must not be used to administer Busulfan Accord. For single use only. Use only a clear solution without turbidity. Storage Unopened vials:Store in a refrigerator (2°C - 8°C). Diluted solution:Chemical and physical stability after dilution with glucose 5% or sodium chloride 0.9% solution for injection has been demonstrated for 4 hours (including infusion time) at 20°C - 25°C or 15 hours after dilution when stored at 2°C - 8°C, followed by 3 hours at 20°C - 25°C (including infusion time). From a microbiological point of view, the diluted solution should be used immediately.

3. PROCEDURE FOR PROPER DISPOSAL OF UNUSED MEDICINE

Unused product or waste materials should be disposed of in accordance with local regulations for cytotoxic medicines.