Busulfan Glenmark 6 mg/ml concentrate for infusion solution EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• If you get any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of this leaflet

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

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

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

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

In adults, busulfan is used in combination with cyclophosphamide.

In newborns, children, and adolescents, busulfan 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 Glenmark

Do not use Busulfan Glenmark

• 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

Talk to your doctor or pharmacist before starting to use Busulfan Glenmark.

Busulfan is a potent cytotoxic medicine that causes a significant decrease in blood cells. At the recommended dose, this is the desired effect. For this reason, close monitoring is required. The use of busulfan 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 taking any other medicines.

Blood clots may form in small blood vessels after haematopoietic cell transplantation (HCT) when high doses of your treatment are used in combination with other medicines.

Other medicines and Busulfan Glenmark

Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines, including medicines obtained without a prescription. Busulfan 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 these may increase the occurrence of adverse effects.

The use of paracetamol during the 72 hours before or during administration of busulfan 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 or pharmacist before using this medicine.

Women must not be pregnant during treatment with busulfan or within 6 months after treatment has ended. Women must stop breastfeeding before starting treatment with Busulfan Glenmark. Effective contraceptive methods must be used when either partner is receiving treatment with busulfan. You may be unable to conceive (infertility) after treatment with busulfan. If you wish to have children, you should consult your doctor before treatment. Busulfan may cause symptoms of menopause and in prepubescent girls may prevent the onset of puberty.

Men treated with busulfan are advised not to father children during treatment and for at least 6 months after treatment has ended.

3. How to use Busulfan Glenmark

Dosage and administration:

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

In adults:

Busulfan Glenmark in combination with cyclophosphamide:

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

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

The recommended dose of Busulfan 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 will be administered every 6 hours for 4 consecutive days prior to transplantation.

Medications prior to administration of Busulfan Glenmark:

Before receiving Busulfan, 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 may cause adverse effects, although not everyone experiences 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), 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 possible adverse effects 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 mucous membrane of the mouth, vomiting, abdominal pain, diarrhea, constipation, heartburn, anal discomfort, fluid in the abdomen. Hepatic: enlargement of the 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 production, 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 mucous membranes. 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 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 the 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 clouding).

Menopausal symptoms and female infertility.

Brain abscesses. Skin inflammation, systemic infection.

Liver disorders.

Increased lactate dehydrogenase levels in blood.

Increased blood uric acid and urea levels.

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: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Busulfan Glenmark

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

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

Closed vial:

Store in a refrigerator (between 2°C and 8°C). Keep the vial in the outer packaging to protect it from light.

Reconstituted solution:

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

• 8 hours (including infusion time) after dilution when stored at 20°C ± 5°C,

or

• 12 hours after dilution when stored between 2°C and 8°C, followed by 3 hours at 20°C ± 5°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 packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Busulfan Glenmark

• The active substance is busulfan. One ml of concentrate contains 6 mg of busulfan (60 mg in the 10 ml vial). After dilution: 1 ml of solution contains approximately 0.5 mg of busulfan.
• The other excipients are dimethylacetamide and macrogol 400.

Appearance of the product and contents of the container

Busulfan Glenmark is a clear, colourless solution.

10 ml of concentrate for infusion solution are supplied in clear type I glass vials with a chlorobutyl rubber stopper coated with Flurotec, sealed with an orange flip-off aluminium cap.

Each carton contains 1 vial or a multiple pack of 8 vials.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:

Glenmark Arzneimittel GmbH
Industriestr. 31
82194 Gröbenzell
Germany

Manufacturer:

apis labor GmbH
Resslstraße 9
9065 Ebenthal in Kärnten
Austria

Further information about this medicinal product can be requested from the local representative of the Marketing Authorisation Holder:

Glenmark Farmacéutica, S.L.U.
C/ Retama 7, 7th floor
28045 Madrid
Spain

This medicinal product is authorised in the European Economic Area member states under the following names:

Denmark: Busulfan Zentiva 6 mg/ml concentrate for solution for infusion
France: BUSULFAN KOANAA 6 mg/ml solution to be diluted for infusion
Germany: Busulfan Koanaa 6 mg/ml concentrate for preparation of infusion solution
Italy: Busulfan Koanaa
Spain: Busulfano Glenmark 6 mg/ml concentrate for solution for infusion EFG
Sweden: Busulfan Zentiva

Date of the most recent review of this leaflet: September 2025

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios) http://www.aemps.gob.es

This information is intended for healthcare professionals only:

PREPARATION GUIDE

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

Read this guide before preparing and administering Busulfan Glenmark.

1. PRESENTATION

Busulfan Glenmark is supplied as a clear, colourless solution in 10 ml clear type I glass vials. Busulfan Glenmark must be diluted before administration.

2. RECOMMENDATIONS FOR SAFE HANDLING

Appropriate procedures for handling and disposal of cytotoxic anticancer drugs must be followed. All transfer procedures must strictly comply with 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 Glenmark solution:

• It is recommended to wear gloves and protective clothing.
• If the product (Busulfan Glenmark or a diluted 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 and diluent for the solution:

Busulfan must be diluted prior to use with sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

The volume of diluent should be 10 times the volume of Busulfan, ensuring a final busulfan concentration of approximately 0.5 mg/ml.

The required amounts of Busulfan and diluent for administration are calculated as follows:

For a patient with a body weight of Y kg:

• Amount of Busulfan Glenmark:

Y: patient's body weight (in kg)

D: dose of Busulfan Glenmark (see section 4.2)

• Diluent amount

(A ml of Busulfan Glenmark) x (10) = B ml of diluent

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

Preparation of the infusion solution

The preparation of Busulfan Glenmark must be carried out by healthcare professionals using aseptic transfer techniques.

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

• The calculated volume of Busulfan Glenmark must be withdrawn from the vial.

• The contents of the syringe must be transferred into an intravenous bag (or syringe) already containing the calculated amount of selected diluent. Busulfan Glenmark must always be added to the diluent, and not the reverse. Busulfan Glenmark must not be introduced into an intravenous bag that does not contain sodium chloride 9 mg/ml (0.9%) injection or 5% glucose injection.

• The diluted solution must be carefully mixed by gentle inversion.

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

Diluted busulfan is a clear, colorless 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 or 5% glucose solution.

Any residual medication must not be infused through the administration system, as rapid infusion of Busulfan Glenmark has not been studied and is not recommended.

The total prescribed dose of Busulfan Glenmark must be administered over a period of two or three hours, depending on the conditioning regimen.

Small volumes may 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 Glenmark and flush afterward with sodium chloride 9 mg/ml (0.9%) injection or 5% glucose injection.

No other intravenous solution should be administered concomitantly with this infusion. Polycarbonate syringes must not be used with Busulfan.

Single-use product. Only clear solutions free from particles should be used.

Storage conditions

Unopened vial:

Store in a refrigerator (between 2°C and 8°C). Keep the vial in the outer packaging to protect it from light.

Diluted solution:

Chemical and physical stability during use after dilution in 5% glucose injection or sodium chloride 9 mg/ml (0.9%) has been demonstrated:

• For 8 hours (including infusion time) after dilution when stored at 20°C ± 5°C,

or

• For 12 hours after dilution when stored between 2°C and 8°C, followed by 3 hours at 20°C ± 5°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 all materials that have come into contact with it must be carried out in accordance with local regulations for cytotoxic medicinal products.