Label: Information for the User

BICNU 100 mg Powder and Diluent for Solution for Infusion EFG

Carmustine

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or nurse, even if they are not listed in this label. See section 4.

Bicnu is a medication that contains carmustin. Carmustin belongs to a group of anticancer substances known as nitrosoureas, which act by slowing down the growth of cancer cells.

Bicnu is used as a palliative therapy (alleviating and preventing the suffering of patients) as a single agent or in combination therapy established with other approved anticancer substances for certain types of cancer, such as:

• Brain tumors - glioblastoma, meduloblastoma, astrocytoma, and metastatic brain tumors
• Multiple myeloma (malignant tumor in development from the bone marrow)
• Hodgkin's disease (lymphoid tumor)
• Non-Hodgkin lymphoma (lymphoid tumor)

Carmustin is also used as a conditioning treatment prior to autologous stem cell transplantation (a procedure in which a person receives hematopoietic stem cells, which produce any type of blood cell) in malignant hematological disorders of the lymphatic system such as Hodgkin's lymphoma and non-Hodgkin lymphoma

No use Bicnu

• If you are allergic to carmustine, other nitrosoureas, or any other ingredient in this medication (listed in section 6);

-Bicnu should not be administered to patients with a reduced number of platelets (thrombocytes), white blood cells (leukocytes), or red blood cells (erythrocytes), whether it is due to chemotherapy or other causes;

-if you have severe renal insufficiency;

-in children and adolescents;

-if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Bicnu.

Since the major toxicity of this medication is late bone marrow suppression, your doctor will monitor your blood count at least during the 6 weeks following the administration of the dose. At the recommended dose, Bicnu cycles will not be administered at a frequency greater than 6 weeks. The dose will be confirmed with the blood count.

Before treatment, both your liver and renal function will be checked, and both will be monitored regularly during treatment.

Due to the fact that the use of Bicnu can lead to lung damage, chest X-rays and pulmonary function tests (please see the "Possible adverse effects" section) will be performed.

High-dose carmustine treatment (up to 600 mg/m2) is only performed in combination with subsequent stem cell transplantation. These high doses may increase the frequency or severity of pulmonary, renal, hepatic, cardiac, and gastrointestinal toxicities as well as infections and electrolyte imbalances (low blood levels of potassium, magnesium, and phosphate).

Neutropenic enterocolitis can occur as an adverse event related to chemotherapy therapy.

Patients with multiple simultaneous conditions and a more precarious state of disease have a higher risk of experiencing adverse effects. This is especially important for elderly patients.

Your doctor will advise you on the possibility of lung damage that may occur due to the use of Bicnu and on allergic reactions and their symptoms. If these symptoms appear, you should consult your doctor (see section 4)

Use of Bicnu with other medications

Inform your doctor or pharmacist if you are taking, have recently taken, or may need to take other medications, including over-the-counter medications, such as:

• Phenytoin, used for epilepsy
• Cimetidine, used for stomach problems such as indigestion
• Digoxin, used if you have an abnormal heart rhythm
• Melfalan, anticancer medication

Pregnancy, breastfeeding, and fertility

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

Pregnancy and fertility

Bicnu should not be used during pregnancy as it may harm the fetus. Therefore, Bicnu should not be administered normally to pregnant women. If it is administered during pregnancy, the patient should be informed about the potential risk to the fetus. Women of childbearing age are advised to avoid becoming pregnant.

Male patients should use adequate contraceptive measures during Bicnu treatment for at least 6 months.

Breastfeeding

You should not breastfeed while taking this medication.

Driving and operating machinery

The effect of this medication on driving and operating machinery is unknown. You should consult your doctor before driving or using any tools or machinery because the amount of alcohol in this medication may reduce your ability to drive or operate machinery.

Bicnu contains propylene glycol

The propylene glycol in this medication may have the same effects as consuming alcohol and increase the likelihood of side effects.

Do not use this medication in children under 5 years old.

Use this medication only if recommended by a doctor. Your doctor may perform additional checks while you are taking this medication

Bicnu will always be administered by healthcare professionals with experience in the use of anticancer agents.

This medication is administered intravenously.

Adults

The dose depends on your medical condition, body size, and response to treatment. It is usually administered at least every 6 weeks. The recommended dose of Bicnu as a single agent in patients who have not been previously treated is 150 to 200 mg/m2intravenously every 6 weeks. This can be administered as a single dose or divided into two daily injections of 75 to 100 mg/m2over two consecutive days. The dose will also depend on whether Bicnu is administered with other anticancer drugs.

The doses will be adjusted based on your response to treatment.

The recommended dose of carmustine administered in combination with other chemotherapy agents before a hematopoietic stem cell transplant is 300- 600 mg/m2intravenously.

Your blood count will be monitored frequently to prevent bone marrow toxicity and adjust the dose if necessary.

Administration method

Intravenous administration should be carried out through infusion.

Bicnu is administered through a vein via a drip over a period of one to two hours. The infusion time should not be less than one hour to avoid burns and pain at the injection site. The injection site will be monitored during administration.

The duration of treatment will be determined by your doctor and may vary for each patient.

Use in elderly patients

Bicnu can be used with caution in elderly patients. Renal function will be closely monitored.

In elderly patients, the incidence of oral mucositis (inflammation of the mucous membranes in the mouth) is higher when a high dose of carmustine is administered.

If you take more Bicnu than you should

Since it will be the doctor or nurse who administers this medication, it is unlikely that you will receive an incorrect dose. Inform your doctor or nurse if you have any doubts about the amount of medication you are receiving.

If you have any other questions about the use of this medication, consult your doctor, pharmacist, or nurse.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Poison Control Service. Phone 91 562 04 20, indicating the medication and the amount ingested.

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

Inform your doctor or nurse immediately if you experience any of the following symptoms:

Sudden shortness of breath, difficulty breathing, swelling of the eyelids, face, or lips, skin rash or itching (especially if it affects the entire body), and a feeling of fainting. These may be signs of a severe allergic reaction.

Bicnu may cause the following side effects:

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

• Late myelosuppression (decrease in blood cells in the bone marrow);
• Ataxia (lack of voluntary movement coordination);
• Dizziness;
• Headache
• Transient conjunctival redness, blurred vision, retinal hemorrhage;
• Hypotension (low blood pressure) in high-dose therapy;
• Phlebitis (inflammation of the veins);
• Respiratory disorders (pulmonary disorders) with breathing problems;
• Severe nausea and vomiting; starting 2-4 hours after administration and lasting up to 4-6 hours;
• Cutaneous inflammation (dermatitis) when used on the skin;
• A transient hyperpigmentation (darkening of a skin area or nails) after accidental skin contact

Common(may affect 1 in 10 people)

• Acute leukemia and bone marrow dysplasias (abnormal development of the bone marrow) after long-term use; Possible symptoms include: bleeding gums, bone pain, fever, frequent infections, frequent or severe nasal bleeding, swollen lymph nodes in and around the neck, forearm, abdomen, or groin, pale skin, difficulty breathing, weakness, fatigue, or general lack of energy;
• Anemia (decrease in the number of red blood cells in the blood);
• Encephalopathy (brain disorder) in high-dose therapy;
• Loss of appetite (anorexia);
• Constipation;
• Dyspepsia;
• Inflammation of the mouth and lips;
• Reversible hepatotoxicity in high-dose therapy, up to 60 days after administration. This may manifest as an increase in liver enzymes and bilirubin.
• Alopecia (hair loss);
• Skin redness;
• Reactions at the injection site

Rare(may affect up to 1 in 1,000 people)

• Veno-occlusive disease (progressive blockage of veins) in high-dose therapy; Possible symptoms include: accumulation of fluid in the abdomen, enlargement of the spleen, severe bleeding from the esophagus, yellow discoloration of the skin, and white skin around the eyes;
• Respiratory problems due to a type of lung disease with fibrosis interstitial (with lower doses);
• Renal toxicity;
• Gynecomastia (breast growth in men);
• Inflammation of the optic nerve and adjacent retina in the eye;
• Bleeding from the intestinal tract

Very rare(may affect up to 1 in 10,000 people)

• Inflammation of the venous wall with associated thrombosis (thrombophlebitis)

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

• Allergic reactions;
• Muscle pain;
• Secondary tumors (cancers caused by radiation or chemotherapy);
• Seizures (attacks) including "status epilepticus";
• Tissue damage due to leakage at the injection site;
• Infertility;
• Embryonic/fetal developmental insufficiency in pregnant women;
• Any sign of infection;
• Fast heart rate, chest pain.
• Alterations in electrolyte balance (low levels of potassium, magnesium, phosphate in the blood);
• Abdominal pain (neutropenic enterocolitis)

Reporting of 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 leaflet. You can also report them directly through the Spanish 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.

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

Do not use this medication after the expiration date that appears on the label and on the packaging after “CAD.” The expiration date refers to the last day of that month.

This medication will be stored by your doctor or healthcare professional.

The unopened vial of powder medication should be stored in a refrigerator (2°-8°C).

After reconstitution according to recommendations, the carmustine injectable is stable for 480 hours in refrigeration (2°C -8°C) and 24 hours at room temperature (25°C ±2°C) in a glass container. Examine the reconstituted vials for crystal formation before use. If crystals are observed, they can be redissolved by warming the vial to room temperature with agitation.

Diluted to 500 ml with sodium chloride 0.9% for injection or with Dextrose 5% for injection, in glass or polypropylene containers, results in a solution that must be used within 4 hours at 25°C ± 2°C and must be protected from light. These solutions are also stable for 48 hours in a refrigerator (2°C-8° C) protected from light.

A sign of degradation is the appearance of an oil film at the bottom of the vial. If this occurs, this medication should not be used further. When you are unsure about whether the product is cooled adequately, you should immediately inspect all vials in the box. For verification, hold the vial in a clear light. Carmustine appears with small amounts of dry scales or rigid dry mass.

Medications should not be thrown down the drains or in the trash. If in doubt, ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Contents of Bicnu

The active principle is carmustine.

A 30 ml vial contains 100 mg of carmustine and a 5 ml vial contains 3 ml of sterilized solvent (propylene glycol).

Remaining excipients

Powder: No excipients

Solvent: propylene glycol

Appearance of the product and contents of the packaging

Powder and solvent for perfusion solution

Powder for reconstitution: yellowish powder.

Appearance of the solution: colorless to light yellow.

Powder: amber type I glass vial (30 ml) sealed with a dark gray bromobutyl rubber stopper and an aluminum seal with a polypropylene cap.

Solvent: Type I glass vial (5 ml) sealed with a dark gray bromobutyl rubber stopper and an aluminum seal with a polypropylene cap.

Marketing Authorization Holder

Laboratorios Tillomed Spain, S.L.U.

C/ Cardenal Marcelo Spínola 8, 1st floor-door F

28016 Madrid

Spain

Responsible for manufacturing1

MIAS Pharma Limited

Suite 2, Stafford House, Strand Road

Portmarnock, Co. Dublin

Ireland

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

[1]Only the center that actually performs the release will be indicated in the marketed product.

For further information about this medicine, please contact the local representative of the marketing authorization holder:

Zentiva Spain S.L.

Avenida de Europa, 19, Building 3, 1st floor.

28224 Pozuelo de Alarcón, Madrid

Spain

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

Spain: Bicnu 100 mg Powder and solvent for perfusion solution EFG

Last review date of this leaflet: November 2024.

For detailed and updated information about this medicine, please visit the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/