Leaflet: information for the user

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

Read this 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, consult your doctor or pharmacist..
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isBusulfan Glenmarkand what it is used for

2. What you need to know before starting to useBusulfan Glenmark

3. How to useBusulfan Glenmark

4. Possible side effects

5. Storage ofBusulfan Glenmark

6. Contents of the pack and additional information

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

Busulfano is used in adults, newborns, children, and adolescents aspre-transplant treatment.

In adults, Busulfano is used in combination with cyclophosphamide.

In newborns, children, and adolescents, Busulfano 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.

No use Busulfano Glenmark

• if you are allergic to Busulfano or any of the other ingredients in 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 Busulfano.

Busulfano 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 control should be performed. There is a possibility that the use of Busulfano may increase the risk of developing another malignant tumor in the future.

You must inform your doctor:

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

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

Other Medications and Busulfano Glenmark

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

You should exercise special caution 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 medication 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 prior to or during the administration of Busulfano should be done with caution.

Pregnancy,Lactation,Fertility

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Women should not be pregnant during treatment with Busulfano or in the 6 months following its completion. Women should discontinue breastfeeding before starting treatment with Busulfano Glenmark. Effective contraceptive methods should be used when one of the partners is being treated with Busulfano. It may be possible that you cannot become pregnant (infertility) after treatment with Busulfano. If you wish to have children, you should consult with your doctor before treatment. Busulfano may produce menopausal symptoms and in preadolescent girls may prevent the onset of puberty.

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

Dose and administration:

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

In adults:

Busulfano Glenmark in combination with cyclophosphamide:

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

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

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

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

Medications prior to Busulfano Glenmark administration:

Before receiving Busulfano, you will be treated with:

• anticonvulsant medications to prevent seizures (phenytoin or benzodiazepines) and
• antiemetic medications to prevent vomiting.

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

Severe side effects

The most severe side effects associated with treatment with Busulfano 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. 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:increased heart rate, increased or decreased blood pressure, vasodilation (widening of blood vessels), 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:enlargement of the liver, jaundice, bile duct obstruction.Skin:eruption, itching, hair loss.Musculoskeletal and skeletal: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, 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, vomiting blood.Skin:skin color disorders, skin redness, skin peeling.Renal:increased nitrogenous components in the blood fluid, 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 in the blood.Gastrointestinal:bleeding from the stomach and/or intestine.

Unknown frequency (cannot be estimated from available data)

Sexual gland dysfunction.

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

Menopause symptoms and female infertility.

Cerebral abscesses. Generalized 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 type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears onthepackageafter CAD. The expiration date is the last day of the month indicated.

Sealed vial:

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

Diluted solution:

The chemical and physical stability during use after dilution in the glucose 5% injectable 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 of storage at 20 °C ± 5 °C (including infusion time).

Do not freeze

Medicines should not be disposed of through drains or in the trash. Ask your pharmacisthow to disposeofthepackaging and of themedicines that you no longerneed.This will help protect the environment.

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 otherexcipientsare dimethylacetamide and macrogol 400

Appearance of the product and contents of the package

Busulfan Glenmark is a transparent 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 fluoroate covered with a sealed aluminum flip-off cap of orange color.

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

Only some package sizes may be marketed.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Glenmark Arzneimittel GmbH

Industriestr. 31

82194 Gröbenzell

Germany

Responsible for manufacturing

apis labor GmbH

Resslstraße 9

9065 Ebenthal in Kärnten

Austria

This medicinal product is authorized in the member states of the European Economic Area with the following names:

DanishBusulfan Zentiva6 mg/ml concentrate for infusion solution

FrenchBUSULFAN KOANAA 6 mg/ml solution to be diluted for infusion

GermanBusulfan Koanaa 6 mg/ml Concentrate for the preparation of an infusion solution

ItalianBusulfan Koanaa

SpanishBusulfano Glenmark 6 mg/ml concentrate for infusion solution EFG.

SwedishBusulfan Zentiva

Last revision date of thisleaflet: August 2022

The detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Medical Devices http://www.aemps.gob.es

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This information is intended solely for healthcare professionals:

PREPARATION GUIDE

Busulfan Glenmark 6 mg/ml concentrate for infusion solution EFG

Read this guide before preparation and administration of Busulfan Glenmark.

1. Presentation

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

1. RECOMMENDATIONS FOR SAFE HANDLING

Proper handling and disposal procedures for anticancer drugs 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 Glenmark solution:

• It is recommended to use gloves and protective clothing.
• If the product (Busulfan Glenmark or a solution of the same diluted) 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%) injection solution or with 5% glucose injection solution.

The amount of diluent must be 10 times the volume of Busulfan, which ensures 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, the (A) ml of Busulfan Glenmark 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

The preparation of Busulfan Glenmark must be performed by healthcare professionals using sterile transfer techniques.

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

• Extract the calculated volume of Busulfan Glenmark from the vial.
• Introduce the contents of the syringe into an intravenous bag (or syringe) that already contains the calculated amount of diluent. Always add Busulfan Glenmark to the diluent, not the other way around. Do not introduce Busulfan Glenmark into an intravenous bag that does not contain sodium chloride 9 mg/ml (0.9%) injection solution or 5% glucose injection solution.

• Mix the diluted solution carefully by inversion agitation.

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

Busulfan diluted is a transparent and colorless solution.

Instructions for use

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

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

The total dose of Busulfan Glenmark prescribed should be administered within a period of 2 or 3 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 a perfusion device with a minimum dead space (e.g. 0.3-0.6 ml). Purgate with the medication solution before infusion of Busulfan Glenmark and wash afterwards with sodium chloride 9 mg/ml (0.9%) injection solution or glucose (5%).

No other intravenous solution should be administered concomitantly with this infusion. Do not use polycarbonate syringes with Busulfan.

Single-use product. Only usable solutions that are transparent and free of particles.

Storage conditions

Sealed vial:

Store in refrigerator (between 2°C and 8°C), store 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 sodium chloride 9 mg/ml (0.9%) injection solution has been demonstrated

• During 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

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations for cytotoxic drugs.