Bicnu 100 mg powder and solvent for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

BiCNU 100 mg Powder and solvent for solution for infusion EFG

Carmustine

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, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What Bicnu is and what it is used for

Bicnu is a medicine containing carmustine. Carmustine belongs to a group of anticancer agents known as nitrosoureas, which work by slowing the growth of cancer cells.

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

• Brain tumors – glioblastoma, medulloblastoma, astrocytoma, and metastatic brain tumors
• Multiple myeloma (a malignant tumor arising in the bone marrow)
• Hodgkin’s disease (a lymphoid tumor)
• Non-Hodgkin’s lymphoma (a lymphoid tumor)

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

2. What you need to know before starting to take Bicnu

Do not use Bicnu

• if you are allergic to carmustine, to other nitrosoureas, or to any of the other ingredients of this medicine (listed in section 6);

• Bicnu must not be given to patients who have low platelet counts (thrombocytes), low white blood cell counts (leukocytes), or low red blood cell counts (erythrocytes), whether due to chemotherapy or other causes;

• if you have severe renal failure;

• in children and adolescents;

• if you are pregnant or breastfeeding.

Warnings and precautions

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

Since the main toxicity of this medicine is delayed bone marrow suppression, your doctor will monitor your blood counts for at least 6 weeks following administration of the dose. At the recommended dose, Bicnu cycles should not be administered more frequently than every 6 weeks. The dose will be confirmed based on your blood counts.

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

Because the use of Bicnu may cause lung damage, chest X-rays and pulmonary function tests will be performed (please see section "Possible side effects").

Treatment with high doses of carmustine (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).

Abdominal pain (neutropenic enterocolitis) may occur as an adverse event related to chemotherapy agents.

Patients with multiple concurrent medical conditions and a more unstable disease status are at higher risk of experiencing adverse effects. This is especially important for elderly patients.

Your doctor will advise you about the possibility of lung damage that may occur with the use of Bicnu, as well as allergic reactions and their symptoms. If such symptoms occur, you must consult your doctor (see section 4).

Use of Bicnu with other medicines

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

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

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 medicine.

Pregnancy and fertility

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

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

Breastfeeding

You must not breastfeed while taking this medicine.

Driving and use of machinery

The effect of this medicine on driving and operating machinery is unknown. You should consult your doctor before driving or operating any tools or machinery, as the alcohol content of this medicine may reduce your ability to drive or operate machinery.

Bicnu contains propylene glycol

The propylene glycol in this medicine may have effects similar to alcohol consumption and may increase the likelihood of side effects.

Do not use this medicine in children under 5 years of age.

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

3. How to use Bicnu

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

This medicine is administered intravenously.

Adults

The dose depends on your medical condition, body size, and response to treatment. It is usually given 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/m² administered intravenously every 6 weeks. This may be given either as a single dose or divided into two daily injections of 75 to 100 mg/m² on two consecutive days. The dose will also depend on whether Bicnu is administered together with other anticancer drugs.

Doses will be adjusted depending on your response to treatment.

The recommended dose of carmustine administered in combination with other chemotherapeutic agents prior to hematopoietic progenitor cell transplantation is 300–600 mg/m² intravenously.

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

Method of administration

Intravenous administration must be performed by infusion.

Bicnu is administered into 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 burning and pain at the injection site. The injection site will be monitored during administration.

The duration of treatment will be determined by the physician and may vary for each patient.

Use in elderly patients

Bicnu may be used with caution in elderly patients. Renal function will be carefully monitored.

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

If you use more Bicnu than you should

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

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

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

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

Any sudden wheezing, difficulty breathing, swelling of the eyelids, face or lips, skin rash or itching (especially if it affects the whole body), and feeling faint. These may be signs of a serious allergic reaction.

Bicnu may cause the following adverse effects:

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

• Delayed myelosuppression (reduction in blood cells in the bone marrow);
• Ataxia (lack of voluntary coordination of muscle movements);
• Dizziness;
• Headache;
• Transient eye redness, blurred vision, retinal bleeding;
• Hypotension (low blood pressure) in high-dose therapies;
• Phlebitis (inflammation of the veins);
• Respiratory disorders (pulmonary disorders) with breathing difficulties;
• Severe nausea and vomiting; starting 2–4 hours after administration and lasting up to 4–6 hours;
• When used on the skin, skin inflammation (dermatitis);
• Accidental skin contact may cause transient hyperpigmentation (darkening of an area of skin or nails)

Common (may affect 1 in 10 people)

• Acute leukemia and bone marrow dysplasias (abnormal bone marrow development) after long-term use; symptoms may include: bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps due to swollen lymph nodes in and around the neck, forearm, abdomen, or groin, pale skin, difficulty breathing, weakness, fatigue, or general lack of energy;
• Anaemia (reduction in the number of red blood cells in the blood);
• Encephalopathy (brain disorder) in high-dose therapies;
• Loss of appetite (anorexia);
• Constipation;
• Diarrhoea;
• Inflammation of the mouth and lips;
• Reversible liver toxicity in high-dose therapies, up to 60 days after administration. This may manifest as increased 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 therapies; small veins in the liver become blocked. Possible symptoms include: fluid accumulation in the abdomen, spleen enlargement, severe bleeding from the esophagus, yellowing of the skin, and white part of the eyes;
• Respiratory problems due to a type of lung disease involving scarring of tissue from interstitial fibrosis (with lower doses);
• Kidney toxicity;
• Gynaecomastia (breast enlargement 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 (frequency cannot be estimated from available data)

• Allergic reactions;
• Muscle pain;
• Secondary tumours (cancers caused by radiation or chemotherapy);
• Seizures (fits), including "status epilepticus";
• Tissue damage due to leakage at the injection site;
• Infertility;
• Impaired embryonic/fetal development in pregnant women;
• Any signs of infection;
• Rapid heartbeat, chest pain;
• Electrolyte imbalances (low levels of potassium, magnesium, phosphate in the blood);
• Abdominal pain (neutropenic enterocolitis)

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can 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 Bicnu

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

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

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

The unopened powder vial must be stored in the refrigerator (2°C–8°C).

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

The reconstituted solution diluted up to 500 ml with 0.9% Sodium Chloride for Injection or 5% Dextrose for Injection in glass or polypropylene containers results in a solution that must be used within 4 hours at 25°C ± 2°C and should be protected from light. These solutions are also stable for up to 48 hours when refrigerated (2°C–8°C) and protected from light.

An indication of decomposition is the appearance of an oily film at the bottom of the vial. If this occurs, this medicine must not be used. When you are uncertain whether the product has been adequately refrigerated, inspect each and every vial in the pack immediately. For inspection, hold the vial up to a bright light. Carmustine may appear with small amounts of dry flakes or dry rigid mass.

Medicines must not be disposed of via wastewater or household waste. If you are unsure how to dispose of medicines or packaging that you no longer need, ask your pharmacist. This will help protect the environment.

6. Contents of the pack and other information

Contents of Bicnu

The active substance is carmustine.

One 30 ml vial contains 100 mg of carmustine and one 5 ml vial contains 3 ml of sterile solvent (propylene glycol).

Other ingredients

Powder: No excipients

Solvent: propylene glycol

Nature of the product and contents of the container

Powder and solvent for solution for infusion

Yellowish powder for reconstitution.

Appearance of the solution: colourless to pale yellow.

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

Solvent: glass type I vial (5 ml) sealed with a grey bromobutyl rubber stopper and an aluminium seal with a polypropylene cap.

Marketing Authorisation Holder

Laboratorios Tillomed Spain, S.L.U.

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

28016 Madrid

Spain

Manufacturer responsible [1]

SGS Pharma Magyarorszag Kft.

Derkovits Gyula Utca 53,

Budapest XIX, 1193,

Hungary

Tillomed Malta Limited,

Malta Life Sciences Park,

LS2.01.06 Industrial Estate,

San Gwann, SGN 3000, Malta

[1] Only the site actually performing the release will be indicated on the marketed product.

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

Zentiva Spain S.L.

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

28224 Pozuelo de Alarcón, Madrid

Spain

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

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

Date of the most recent revision of this leaflet: November 2024.

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) http://www.aemps.gob.es/