BUSULFAN GLENMARK 6 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Leaflet: information for the user

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

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

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

Contents of the leaflet

1. What is Busulfan Glenmark and what is it used for
2. What you need to know before starting to use Busulfan Glenmark
3. How to use Busulfan Glenmark
4. Possible side effects
5. Storage of Busulfan Glenmark
6. Package contents and additional information

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

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

Busulfan is used in adults, newborns, children, and adolescents as pre-treatment for transplantation.

In adults, Busulfan is used in combination with cyclophosphamide.

In newborns, children, and adolescents, Busulfan 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.

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

Do not use Busulfan Glenmark

• if you are allergic to Busulfan or any of the other components of this medication (listed in section 6).
• if you are pregnant or think you may be pregnant.

Warnings and precautions

Consult your doctor or pharmacist before starting to use Busulfan.

Busulfan is a potent cytotoxic medication that causes a significant decrease in blood cells. At the recommended dose, this is the desired effect. For this reason, strict monitoring is required. It is possible that the use of Busulfan may increase the risk of developing another malignant tumor in the future.

You should inform your doctor:

• if you have a liver, kidney, heart, or lung problem,
• if you have a history of seizures,
• if you are taking other medications.

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

Other medications and Busulfan Glenmark

Tell your doctor or pharmacist if you are using, have recently used, or may need to use any other medication, including over-the-counter medications. Busulfan may interact with other medications.

You should be especially careful if you are using itraconazole and metronidazole (used to treat certain types of infections) or cetobemidone (used to treat pain), or deferasirox (a medication used to remove excess iron from the body), as it may increase the occurrence of side effects.

The use of paracetamol during the 72 hours prior to or during the administration of Busulfan 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 or pharmacist before using this medication.

Women should not be pregnant during treatment with Busulfan or in the 6 months following its completion. Women should stop breastfeeding before starting treatment with Busulfan Glenmark. Effective contraceptive methods should be used when one partner is being treated with Busulfan. It is possible that you may not be able to become pregnant (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 may prevent the onset of puberty in pre-adolescent girls.

Men treated with Busulfan are advised not to father children during and up to 6 months after completing treatment.

3. How to use Busulfan Glenmark

Dose 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 before the transplant.

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

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

• Each infusion lasts 2 hours.
• Busulfan will be administered every 6 hours for 4 consecutive days before the transplant.

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 side effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Severe side effects

The most severe side effects associated with treatment with Busulfan or the transplant procedure may include a decrease in the count of circulating blood cells (an effect intended with the medication to prepare you for the transplant), infections, liver disorders such as obstruction of a liver vein, graft-versus-host disease (the graft reacts against your body), and pulmonary complications. Your doctor will regularly monitor your blood counts and liver enzymes to detect and treat these effects.

Other side effects may include:

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

Blood:decrease in the number of circulating blood cells (red and white) 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:increased heart rate, increased or decreased blood pressure, vasodilation (increase in blood vessel caliber), 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 mouth mucosa, vomiting, abdominal pain, diarrhea, constipation, chest burning, anal discomfort, and fluid in the abdomen. Hepatic:increased liver size, jaundice, and obstruction of a liver vein. Skin:rash, itching, and hair loss. Musculoskeletal and bone:back pain, muscle and joint pain. Renal:increased creatinine elimination, urinary discomfort, and 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, and mucosal inflammation. Additional tests:elevated liver enzyme levels 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:changes and abnormalities in heart rhythm, fluid retention or inflammation around the heart, and decreased ejection fraction. Respiratory:increased respiratory rate, respiratory failure, alveolar hemorrhage, asthma, collapse of small areas of the lung, and fluid around the lung. Gastrointestinal:esophageal mucosa inflammation, intestinal paralysis, and vomiting blood. Skin:skin color disorders, skin redness, and skin peeling. Renal:increased nitrogenous components in the blood, moderate renal failure, and renal disorder.

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

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

Frequency not known (cannot be estimated from available data)

Sexual gland dysfunction.

Eye disorders, including cataract and blurred vision.

Menopausal symptoms and female infertility.

Brain abscesses. Skin inflammation, generalized infection.

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 side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Busulfan Glenmark

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the packaging after CAD. The expiration date is the last day of the month indicated.

Closed vial:

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

Diluted solution:

The chemical and physical stability during use after dilution in 5% glucose injection solution or 9 mg/ml (0.9%) sodium chloride 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 of storage at 20°C ± 5°C (including infusion time).

Do not freeze

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Container Contents and Additional Information

Composition of Busulfan Glenmark

• The active ingredient 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

Product Appearance and Container Contents

Busulfan Glenmark is a clear and colorless solution.

10 ml of concentrate for solution for infusion are presented in transparent type I glass vials with a rubber stopper coated with chlorobutyl fluorotec covered with an orange flip-off aluminum cap.

Each box contains 1 vial or multiple packaging of 8 vials.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Glenmark Arzneimittel GmbH

Industriestr. 31

82194 Gröbenzell

Germany

Manufacturer:

apis labor GmbH

Resslstraße 9

9065 Ebenthal in Kärnten

Austria

You can request more information about this medicine by contacting the local representative of the Marketing Authorization Holder:

Glenmark Farmacéutica, S.L.U.

C/ Retama 7, 7th floor

28045 Madrid

Spain

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

Denmark Busulfan Zentiva 6 mg/ml concentrate for infusion solution

France BUSULFAN KOANAA 6 mg/ml solution for infusion

Germany Busulfan Koanaa 6 mg/ml concentrate for solution for infusion

Italy Busulfan Koanaa

Spain Busulfano Glenmark 6 mg/ml concentrate for solution for infusion EFG.

Sweden Busulfan Zentiva

Date of the last revision of thisleaflet:August 2022

Detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products http://www.aemps.gob.es

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This information is intended only for healthcare professionals:

PREPARATION GUIDE

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

Read this guide before preparing and administering Busulfano Glenmark.

1. Presentation

Busulfano Glenmark is presented as a clear and colorless solution in 10 ml transparent type I glass vials. Busulfano Glenmark must be diluted before administration.

1. Recommendations for Safe Handling

Adequate handling and disposal procedures for anticancer medicines should be taken into account. All transfer procedures require strict adherence to aseptic techniques; preferably, a safety cabinet with vertical laminar flow should be used.

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

• It is recommended to use gloves and protective clothing.
• If the product (Busulfano Glenmark or a diluted solution) comes into contact with the skin or mucous membranes, wash the area immediately and abundantly with water.

Calculation of the amount of Busulfan and diluent for the solution:

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

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

The amount of busulfan and diluent for administration will be 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)

• Amount of diluent

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

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

Preparation of the infusion solution

The preparation of Busulfano Glenmark should be performed by healthcare professionals using sterile transfer techniques.

• A non-policarbonate syringe with a needle should be used:

• The calculated volume of Busulfan Glenmark should be withdrawn from the vial.
• The contents of the syringe should be introduced into an intravenous bag (or syringe) that already contains the calculated amount of the chosen diluent. Busulfan Glenmark should always be added to the diluent, not the other way around. Busulfan Glenmark should not be introduced into an intravenous bag that does not contain sodium chloride 9 mg/ml (0.9%) injectable solution or 5% glucose injectable solution.

• The diluted solution should be carefully mixed by inversion.

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

Diluted Busulfan is a clear and colorless solution.

Instructions for use

Before and after each infusion, the catheterization circuit should be flushed with approximately 5 ml of sodium chloride 9 mg/ml (0.9%) injectable solution or glucose (5%) solution.

Residual medicine should not be administered through the administration system, as rapid infusion of Busulfano Glenmark has not been studied and is not recommended.

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

Small volumes can be administered over 2 hours using an electronic syringe pump. In this case, it is recommended to use an infusion device with a minimum dead space (e.g., 0.3-0.6 ml). Purge with the medicine solution before infusing Busulfano Glenmark and flush afterwards with sodium chloride 9 mg/ml (0.9%) injectable solution or glucose (5%) injectable solution.

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

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

Storage Conditions

Closed 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:

The chemical and physical stability during use after dilution in 5% glucose injectable solution or sodium chloride 9 mg/ml (0.9%) injectable solution 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 of storage at 20 °C ± 5 °C (including infusion time).

From a microbiological point of view, the diluted solution should be used immediately.

1. PROCEDURE FOR PROPER DISPOSAL

Disposal of unused medicine and all materials that have come into contact with it should be carried out in accordance with local regulations for cytotoxic medicines.