Busulfan Accord 6 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

Busulfan Accord 6 mg/ml concentrate for solution for infusion EFG

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 or pharmacist.
• If you experience any adverse reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet.

Contents of the leaflet

1. What Busulfan Accord is and what it is used for
2. What you need to know 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 Busulfan Accord is and what it is 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 prior to transplantation.

Busulfan Accord is used in adults, newborns, children and adolescents as a preparative treatment prior to transplant.

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

In newborns, children and adolescents, Busulfan Accord is used in combination with cyclophosphamide or melphalan.

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

2. What you need to know before starting to use Busulfan Accord

Do not use Busulfan Accord:

• 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 Accord 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 Accord may increase the risk of developing another malignant tumor 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 taking any other medicines.

After a hematopoietic cell transplant (HCT), high-dose treatment with Busulfan Accord in combination with other medicines may lead to the formation of blood clots in small blood vessels.

Use of Busulfan Accord with other medicines

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. Especially 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.

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), as this may increase the occurrence of adverse effects.

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

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you might be pregnant, or plan to become pregnant, consult your doctor before receiving treatment with Busulfan Accord. Women must not be pregnant during treatment with Busulfan Accord or for 6 months after treatment ends.

Women must stop breastfeeding before starting treatment with Busulfan Accord.

Effective contraceptive methods should be used when either partner is being treated with Busulfan Accord.

You may be unable to conceive a child (infertility) after treatment with busulfan. If you wish to have children, you should consult your doctor before treatment. Busulfan Accord may cause symptoms of menopause and, in prepubescent girls, may prevent the onset of puberty.

Men treated with Busulfan Accord are advised not to father children during treatment and for 6 months after treatment ends.

3. How to use Busulfan Accord

Dosage and administration:

The dose of Busulfan Accord will be calculated based on your body weight.

In adults:

Busulfan in combination with cyclophosphamide:

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

Busulfan in combination with fludarabine:

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

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

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

• Each infusion lasts 2 hours.
• Busulfan Accord will be administered every 6 hours for 4 consecutive days prior to transplantation.

Medications prior to administration of Busulfan:

Before receiving Busulfan Accord, 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 with the medicine to prepare you for transplant engraftment), infections, liver disorders such as hepatic vein obstruction, 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):

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 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, chest burning, anal discomfort, fluid in the abdomen. Hepatic: enlarged liver, jaundice, obstruction of a liver vein. Skin: rash, itching, hair loss. Musculoskeletal: back pain, muscle and jaw 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 enzymes and weight gain.

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

Nervous system: confusion, nervous system disorders. Nutrition: low sodium levels in blood. 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 disorder.

Uncommon (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 blood. Gastrointestinal: bleeding from the stomach and/or intestine.

Frequency not known (cannot be estimated from available data)

Sex gland dysfunction.

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

Increased blood pressure in the blood vessels of the lungs (pulmonary hypertension).

Menopausal symptoms and female infertility.

Brain abscesses. Skin inflammation, systemic infection.

Liver disorders.

Increased blood lactate dehydrogenase.

Increased blood uric acid and urea.

Incomplete tooth development.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is an 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 Accord

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 carton following EXP.

Closed vial:

Store in a refrigerator (2 °C - 8 °C).

After dilution:

Chemical and physical in-use stability has been demonstrated after dilution with 5% glucose solution or 9 mg/mL (0.9%) sodium chloride solution for:

• 4 hours (including infusion time) after dilution when stored at 20 °C – 25 °C.
• 15 hours after dilution when stored at 2 °C – 8 °C, followed by an additional 3 hours at 20 °C – 25 °C (including infusion time).

Do not freeze.

From a microbiological standpoint, the product should be used immediately after dilution. If not used immediately, the conditions of storage during use and the duration prior to 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 and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Busulfan Accord

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

Nature and contents of the container

Busulfan Accord is a concentrate for solution for infusion supplied in clear glass vials. Each vial contains 10 ml of concentrate containing 60 mg of busulfan.

Busulfan Accord is a clear, colourless solution free from visible particles, available in pack sizes containing either 1 vial or 8 vials of 10 ml concentrate for solution for infusion.

Some pack sizes may not be marketed.

When diluted, Busulfan Accord yields a clear, colourless solution.

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Spain

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska, 50, 95-200

Pabianice,

Poland

or

Accord Healthcare Single Member S.A.,

64th Km National Road Athens,

Lamia, Schimatari, 32009,

Greece

This medicinal product is authorised in the EEA Member States under the following names:

Member State	Name
Austria	Busulfan Accord 6 mg/ml concentrate for solution for infusion
Czech Republic	Busulfan Accord 6 mg/ml concentrate for infusion solution
Germany	Busulfan Accord 6 mg/ml concentrate for solution for infusion
Spain	Busulfan Accord 6 mg/ml concentrate for infusion solution
France	BUSULFAN ACCORD 6 mg/mL solution to be diluted for infusion
Hungary	Busulfan Accord 6 mg/ml concentrate for infusion solution
Italy	Busulfan Accord
Poland	Busulfan Accord
Portugal	Bussulfan Accord 6 mg/ml concentrate for infusion solution
Romania	Busulfan Accord 6 mg/ml concentrate for perfusion solution
United Kingdom	Busulfan 6 mg/ml concentrate for solution for infusion

Date of the most recent review of this summary: July 2025

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicinal Products and Medical Devices (AEMPS): http://www.aemps.es/

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This information is intended for healthcare professionals only:

PREPARATION GUIDE

BusulfanAccord 6 mg/ml concentrate for solution for infusion

Busulfan

Read this guide before preparing and administering Busulfan.

1. PRESENTATION

Busulfan Accord is presented as a clear, colourless solution in 10 ml colourless glass type I vials.

Busulfan Accord must be diluted prior to administration.

2. RECOMMENDATIONS FOR SAFE HANDLING

Appropriate procedures for handling and disposal of anticancer 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 must be exercised when handling or preparing busulfan solution:

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

Calculation of the amount of Busulfan Accord and diluent required for the solution

Before using Busulfan Accord, the product must be diluted with either 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 Busulfan Accord, ensuring a final busulfan concentration of approximately 0.5 mg/ml.

The required amounts of Busulfan Accord and diluent for administration are 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 dilute
6 (mg/ml)

Y: patient's body weight in kg

D: busulfan dose (see Summary of Product Characteristics, section 4.2.)

• Diluent volume:

(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 9 mg/ml (0.9%) injection solution or 5% glucose injection solution).

Preparation of the infusion solution

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

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

• withdraw the calculated volume of Busulfan Accord from the vial.

• transfer the contents of the syringe into an infusion bag (or syringe) already containing the calculated volume of the selected diluent. Busulfan Accord must always be added to the diluent, and not the reverse. Do not add Busulfan Accord to an infusion bag that does not contain sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

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

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

After dilution, Busulfan Accord is a clear, colourless solution.

Instructions for use

Before and after each infusion, flush the catheter line with approximately 5 ml of sodium chloride 9 mg/ml (0.9%) 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 Accord must 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 Accord, and flush afterwards with sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

Do not administer any other intravenous solution concomitantly with this infusion.

Polycarbonate syringes must not be used with Busulfan Accord.

Single-use product. 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 for 4 hours (including infusion time) after dilution with 5% glucose or sodium chloride 9 mg/ml (0.9%) solution when stored at 20°C–25°C, or for 15 hours after dilution when stored at 2°C–8°C followed by 3 additional hours at 20°C–25°C (including infusion time).

From a microbiological standpoint, the diluted solution should be used immediately.

1. PROCEDURE FOR PROPER DISPOSAL

Disposal of unused medication and of 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.