Leaflet: information for the user

Carmustine Medac 100 mg powder and solvent for concentrate for solution for infusion

EFG

carmustine

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

Carmustina medac is a medication that contains carmustine. Carmustine belongs to a group of anticancer medications, known as nitrosoureas, which act by slowing down the growth of cancer cells.

Carmustina is indicated for the following malignant neoplasms in monotherapy or in combination with other antineoplastic agents and/or other therapeutic measures (radiation therapy, surgery):

• Brain tumors (glioblastoma, brainstem gliomas, medulloblastoma, astrocytoma, and ependymoma), brain metastases
• Second-line treatment in non-Hodgkin lymphoma and Hodgkin disease
• Tumors of the gastrointestinal tract or digestive tract
• Malignant melanoma (skin cancer)
• As a conditioning treatment prior to autologous hematopoietic stem cell transplantation (AHCT) in malignant hematological disorders (Hodgkin disease/non-Hodgkin lymphoma).

No use Carmustina medac:

• if you are allergic to carmustine or any of the other components of this medication (listed in section 6);
• if you have bone marrow suppression and, as a result, have a reduced number of platelets, white blood cells (leucocytes), or red blood cells (erythrocytes), whether due to chemotherapy or other causes;
• if you have severe kidney failure;
• in children and adolescents;
• if you are breastfeeding.

Warnings and precautions

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

The main adverse effect of this medication is delayed bone marrow suppression, which can manifest as fatigue, skin and mucous membrane bleeding, infections, and fever as a result of blood abnormalities. Therefore, your doctor will monitor your blood counts every week for at least 6 weeks after each dose. Following the recommended dosage, Carmustina medac cycles will not be administered at a frequency greater than every 6 weeks. The dosage will be confirmed based on blood counts.

Before treatment, liver, lung, and kidney function will be evaluated, and monitored periodically during treatment.

Since the use of Carmustina medac can cause lung damage, a chest X-ray and pulmonary function tests will be performed before starting treatment (see also the section "Possible adverse effects").

High-dose Carmustina medac 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 may occur as an adverse event related to chemotherapy treatment.

Your doctor will inform you of the possibility of lung damage and allergic reactions and their symptoms. If these symptoms appear, you should contact your doctor immediately (see section 4).

Children and adolescents

Carmustina medac should not be used in children and adolescents under 18 years old.

Other medications and Carmustina medac

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

• Phenobarbital, used for epilepsy.
• Dexamethasone, used as an anti-inflammatory and immunosuppressant.
• Cimetidine, used for stomach problems such as indigestion.
• Digoxin, used if you have an abnormal heart rhythm.
• Melfalan, a cancer medication.

Carmustina medac with alcohol

The amount of alcohol present in this medication may affect the effects of other medications.

Pregnancy, breastfeeding, and fertility

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

Pregnancy and fertility

Carmustina medac should not be used during pregnancy because it may harm the fetus. Therefore, this medication should not be administered to pregnant women normally. If it is used during pregnancy, the patient should be aware of the possible risk to the fetus. Women of childbearing age are advised to use effective contraceptive methods to avoid becoming pregnant during treatment with this medication and for at least six months after completing treatment.

Male patients should use suitable contraceptive methods during treatment with Carmustina medac and for at least 6 months after completing treatment to avoid their partners becoming pregnant.

Breastfeeding

You should not breastfeed while taking this medication and for 7 days after treatment. The risk in newborns/lactants cannot be ruled out.

Driving and operating machines

The influence of Carmustina medac on the ability to drive and operate machines is negligible or insignificant. You should consult your doctor before driving or operating tools or machines, as the amount of alcohol contained in this medication may affect your ability to drive or operate machines.

Carmustina medac contains ethanol (alcohol)

This medication contains 2.4 g of alcohol (ethanol) per vial, which is equivalent to 25.92 g per maximum dose (10% volume). The amount in the maximum dose (600 mg/m2in a 70 kg patient) of this medication is equivalent to 648 ml of beer or 259 ml of wine.

The amount of alcohol in this medication may affect your ability to drive or operate machinery due to its potential to affect your judgment and reaction time.

If you have epilepsy or liver problems, consult your doctor or pharmacist before taking this medication.

The amount of alcohol in this medication may alter the effects of other medications.

Consult your doctor or pharmacist if you are taking other medications.

If you are pregnant, consult your doctor or pharmacist before taking this medication.

If you have a history of alcohol addiction, consult your doctor or pharmacist before taking this medication.

Carmustina medac will always be administered by a healthcare professional with experience in the use of cancer medications.

Adults

Dosage will depend on the disease, body size, and response to treatment. It is usually administered at least every 6 weeks. The recommended dose of Carmustina medac in monotherapy in previously untreated patients is 150 to 200 mg/m2intravenously every 6 weeks. This amount can be administered as a single dose or divided into daily infusions of 75 to 100 mg/m2, over 2 consecutive days. Dosage will also depend on whether Carmustina medac is administered with other cancer medications.

Doses will be adjusted based on your response to treatment.

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

Frequent blood counts will be monitored to prevent bone marrow toxicity, and the dose will be adjusted as necessary.

Route of administration

After reconstitution and dilution, Carmustina medac is administered intravenously through a drip, protected from light, over a period of 1 to 2 hours. The duration of the infusion should not be less than 1 hour to prevent burning 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.

If you use more Carmustina medac than you should

Since your doctor or nurse will administer 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 have received.

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

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

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

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

Carmustine Medac 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) that may increase the risk of infections if white blood cells decrease
• Ataxia (lack of voluntary movement coordination)
• Dizziness
• Headaches
• Transient conjunctival redness, blurred vision due to retinal hemorrhage
• Hypotension (low blood pressure)
• Phlebitis (inflammation of the veins) associated withpain, swelling, redness, sensitivity
• Respiratory disorders (related to the lungs) with respiratory problems This medicine may cause a severe lung injury (possibly fatal). Lung injury may appear years after treatment. Inform your doctor immediately if you experience any of the following symptoms: difficulty breathing, persistent cough, chest pain, persistent weakness/fatigue
• Severe nausea and vomiting
• When used on the skin, inflammation of the skin (dermatitis)
• Accidental skin contact may cause transient hyperpigmentation (darkening of a skin area or nails)

Common(may affect up to 1 in 10 people)

• Acute leukemias and bone marrow dysplasias (abnormal development of the bone marrow) after prolonged use. Some symptoms include gum bleeding, bone pain, fever, frequent infections, frequent or severe nosebleeds, swollen lymph nodes in and around the neck, armpits, abdomen, or groin, pallor, difficulty breathing, weakness, fatigue, or general decrease in energy.
• Anemia (decrease in the number of red blood cells in the blood)
• Encephalopathy (brain disorder). It may include symptoms ofmuscle weaknessin an area, decreased ability to make decisions orconcentration, involuntary contractions, tremors, difficulty speaking or swallowing, convulsions;
• Anorexia
• Constipation
• Dyspepsia
• Inflammation of the mouth and lips
• Reversible liver toxicity with high-dose treatment. This may cause an increase in liver enzymes and bilirubin (detected by blood analysis)
• Alopecia (hair loss)
• Rubefaction of the skin
• Reactions at the injection site

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

• Thrombophlebitis (progressive obstruction of veins) in which very small (microscopic) veins in the liver are blocked. It may include symptoms of: fluid accumulation in the abdomen, enlarged spleen, severe bleeding from the esophagus, yellow discoloration of the skin and white of the eyes.
• Respiratory problems caused by interstitial fibrosis (with lower doses)
• Renal problems
• Gynecomastia (breast growth in males)

Frequency not known(cannot be estimated from available data)

• Muscle pain
• Convulsions (seizures), including status epilepticus
• Tissue damage due to leaks at the injection site
• Any sign of infection
• Infertility
• Carmustine has been shown to negatively affect fetal development.
• Electrolyte anomalies (and alterations in electrolyte balance (low levels of potassium, magnesium, and phosphate in the blood))

Reporting of side effects

If you experience any type of side effects, consult your doctor, pharmacist, or nurse, even if it's side effects that don't appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute toproviding more information about the safety of this medicine.

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

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

Conserve and transport refrigerated (between 2°C and 8°C).

Conserve the vial and ampoule in the outer packaging to protect them from light.

After reconstitution and dilution

After reconstituting Carmustina medac, it is stable for 3 hours when conserved in a glass container and protected from light.

The solution must be administered within the three hours following reconstitution and dilution of the product. The solution must remain protected from light until the end of administration.

Medicines should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of Carmustine medac

• The active ingredient is carmustine.
• Each vial of powder for concentrate for solution for infusion contains 100 mg of carmustine.
• After reconstitution and dilution, 1 ml of solution contains 3.3 mg of carmustine.
• Excipients:
• Powder: does not contain excipients.
• Solvent: anhydrous ethanol.

Appearance of the product and contents of the package

Carmustine medac is a powder and solvent for concentrate for solution for infusion.

The powder is a white to light yellow powder supplied in a brown glass vial.

The solvent is a transparent, colorless liquid supplied in a transparent glass ampoule.

A package of Carmustine medac contains a vial with 100 mg of powder and an ampoule with 3 ml of solvent.

Holder of the marketing authorization and responsible for manufacturing

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Phone: +49 4103 8006-0

Fax: +49 4103 8006-100

Email: [email protected]

Last review date of this leaflet: 08/2024

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.

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This information is intended solely for healthcare professionals:

This information is a brief description of the preparation and/or handling, incompatibilities, dosage, overdose or monitoring and laboratory investigations based on the current technical dossier.

The powder for concentrate for solution for infusion of Carmustine medac does not contain preservatives and is not designed as a multi-dose vial. Reconstitution and subsequent dilutions must be performed in aseptic conditions.

Following the recommended storage conditions, it is possible to avoid the degradation of the unopened vial until the expiry date indicated on the package.

The lyophilized product does not contain preservatives and is only suitable for single use. The lyophilized product may appear as a fine powder, but handling may make it appear as a more dense and lumpy lyophilized product instead of a powder due to the mechanical instability of the lyophilized powder for suspension. The presence of an oily film may be an indication of the fusion of the drug. These products are not valid for use due to the risk of deviations from the temperature of more than 30 °C. This medicinal product should no longer be used. If there are doubts about whether the product is properly refrigerated, each vial in the package should be inspected immediately. For verification, hold the vial in a bright light.

Reconstitution and dilution of the powder for concentrate for solution for infusion:

Dissolve the 100 mg of carmustine powder for concentrate for solution for infusion with 3 ml of the anhydrous ethanol solvent supplied in the primary packaging (brown glass vial). Carmustine must be dissolved completely in ethanol before adding sterile water for injection preparations. Then, add sterile water for injection preparations in a manner that is sterile, 27 ml to the alcohol solution. The 30 ml mother solution must be mixed well. Reconstitution, following the recommendations, results in a transparent, colorless, or light yellow mother solution.

The 30 ml mother solution must be diluted immediately by adding 30 ml of mother solution to 500 ml of glucose injection solution 50 mg/ml (5%) or to 500 ml of sodium chloride injection solution 9 mg/ml (0.9%) in glass containers. The diluted solution of 530 ml (i.e., the ready-to-use solution) must be mixed for at least 10 seconds before administration.

pH and osmolarity of the ready-to-use infusion solutions are:

pH of 4.0 to 5.0 and 385-397 mOsm/l (if diluted in glucose 50 mg/ml [5%] an injection solution) and

pH of 4.0 to 6.8 and 370-378 mOsm/l (if diluted in sodium chloride 9 mg/ml [0.9%] an injection solution).

Administration form

The reconstituted and diluted solution (i.e., the ready-to-use solution) must be administered intravenously by infusion over a period of one to two hours; administration must be completed within three hours after reconstitution/dilution of the medicinal product. The infusion must be administered with a PE tubing set without PVC. During administration of the medicinal product, the container must be made of suitable glass. In addition, the ready-to-use solutions must be protected from light (e.g., by wrapping the container of the ready-to-use solution with aluminum foil) and preferably stored at temperatures below 20-22 °C, as carmustine degrades more rapidly at higher temperatures.

The infusion must be administered with a PE tubing set without PVC.

The infusion of Carmustine medac for shorter periods may cause intense pain and burning at the injection site. The injection site must be monitored during administration.

Proper handling and disposal of antineoplastics must be followed.

Dosage and laboratory investigations

Initial doses

The recommended dose of Carmustine medac in monotherapy in previously untreated patients is 150 to 200 mg/m2intravenously every 6 weeks. This amount may be administered as a single dose or divided into daily infusions of 75 to 100 mg/m2over two consecutive days.

Carmustine medac may be used in combination with other myelosuppressive drugs or in patients in whom the bone marrow reserve is exhausted. Doses must be adjusted based on the patient's hematological profile, as shown below.

Monitoring and subsequent doses

No new cycle of Carmustine medac should be administered until the circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm3, leukocytes above 4,000/mm3), and this occurs, in general, in six weeks. Blood counts must be monitored frequently, and repeated cycles should not be administered before six weeks due to delayed hematologic toxicity.

Subsequent doses after the initial dose must be adjusted based on the patient's hematological response to the previous dose, both in monotherapy and in combination with other myelosuppressive drugs. The following scheme is suggested as a guide for adjusting the dose:

In cases where the nadir of leukocytes and platelets after the initial dose does not fall in the same row (e.g., leukocytes > 4,000 and platelets <25

No limits are set for the duration of application of carmustine treatment. If the tumor remains incurable or if severe or intolerable adverse reactions occur, treatment with carmustine should be discontinued.

Pre-transplant conditioning treatment with TCHP

In patients with malignant hematological disorders, carmustine is administered in combination with other chemotherapy agents before TCHP in a dose of 300-600 mg/m2intravenously.

Special populations

Pediatric population

Carmustine should not be used in children under 18 years of age due to safety reasons.

Geriatric population

In general, the dose for an elderly patient should be selected with caution, usually starting with the lower end of the dose range, which reflects the higher frequency of hepatic, renal, or cardiac dysfunction, and concomitant diseases or treatment with other medications. Since elderly patients are more likely to have decreased renal function, care should be taken when selecting the dose, and glomerular filtration should be monitored and the dose reduced accordingly.

Renal insufficiency

In patients with renal insufficiency, the dose of Carmustine medac should be reduced if glomerular filtration is decreased.

Compatibility/incompatibility with containers

The intravenous solution is unstable in PVC containers. All plastics that come into contact with the carmustine infusion solution (e.g., infusion equipment, etc.) must be made of polyethylene without PVC; otherwise, glass containers must be used.