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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Carmustina medac 100 mg powder and solvent for concentrate for solution for infusion

PMD

carmustine

Read all of 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, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor or nurse, even if it is not one listed in this leaflet. See section 4.

Leaflet contents

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

1. What Carmustina medac is and what it is used for

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

Carmustine is indicated in the following malignant neoplasms as monotherapy or in combination with other antineoplastic agents and/or other therapeutic measures (radiotherapy, surgery):

• Brain tumors (glioblastoma, brainstem gliomas, meduloblastoma, astrocytoma, and ependymoma), brain metastases
• Second-line treatment for non-Hodgkin's lymphoma and Hodgkin's disease
• Gastrointestinal tract tumors
• Malignant melanoma (skin cancer)
• As conditioning treatment prior to autologous hematopoietic progenitor cell transplantation (HPC) in malignant hematological disorders (Hodgkin's disease / non-Hodgkin's lymphoma).

2. What you need to know before using Carmustina medac

Do not use Carmustina medac:

• if you are allergic to carmustine or to any of the other ingredients of this medicine (listed in section 6);
• if you have bone marrow suppression resulting in reduced numbers of platelets, white blood cells (leukocytes), or red blood cells (erythrocytes), whether due to chemotherapy or other causes;
• if you have severe renal impairment;
• in children and adolescents;
• if you are breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Carmustina medac.

The main adverse effect of this medicine is delayed bone marrow suppression, which may manifest as fatigue, bleeding of the skin and mucous membranes, infections, and fever due to blood abnormalities. Therefore, your doctor will monitor your blood counts weekly for at least 6 weeks after each dose. Following the recommended dosage regimen, cycles of Carmustina medac will not be administered more frequently than every 6 weeks. 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 may cause lung injury, a chest X-ray and pulmonary function tests will be performed before starting treatment (see also section "Possible side effects").

Treatment with high doses of Carmustina medac (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 a therapy-related adverse event following treatment with chemotherapeutic agents.

Your doctor will inform you about the possibility of developing lung injury and allergic reactions, and their symptoms. If these symptoms occur, contact your doctor immediately (see section 4).

Children and adolescents

Carmustina medac must not be used in children and adolescents under 18 years of age.

Other medicines and Carmustina medac

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

• Phenytoin, used in 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.
• Melphalan, a cancer medicine.

Carmustina medac and alcohol

The amount of alcohol present in this medicine may alter the effects of other medicines.

Pregnancy, breastfeeding, and fertility

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

Pregnancy and fertility

Carmustina medac must not be used during pregnancy because it may harm the fetus. Therefore, this medicine is not normally given to pregnant women. If used during pregnancy, patients must be aware of the potential risk to the fetus. Women of childbearing potential should use effective contraceptive methods to avoid pregnancy during treatment with this medicine and for at least six months after completion of treatment.

Male patients must use adequate contraceptive methods during treatment with Carmustina medac and for at least 6 months after completion of treatment to prevent their partners from becoming pregnant.

Breastfeeding

You must not breastfeed while taking this medicine and for 7 days after treatment. Risk to newborns/infants cannot be excluded.

Driving and using machines

The influence of Carmustina medac on the ability to drive and use machines is none or negligible. However, you should consult your doctor before driving or operating tools or machinery, as the amount of alcohol contained in this medicine may affect your ability to drive or operate machines.

Carmustina medac contains ethanol (alcohol)

This medicine contains 2.4 g of alcohol (ethanol) per vial, equivalent to 25.92 g per maximum dose (10% volume). The amount in the maximum dose (600 mg/m² in a 70 kg patient) of this medicine is equivalent to 648 ml of beer or 259 ml of wine.

The amount of alcohol in this medicine may affect your ability to drive or operate machinery, as it may impair your judgment and reaction speed.

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

The amount of alcohol in this medicine may alter the effects of other medicines.

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

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

If you are alcohol-dependent, consult your doctor or pharmacist before taking this medicine.

3. How to use Carmustina medac

Carmustina medac will always be administered by a healthcare professional experienced in the use of anticancer medicines.

Adults

The dosage depends on the disease, body size, and response to treatment. It is usually administered at least every 6 weeks. The recommended dose of Carmustina medac as monotherapy in previously untreated patients is 150 to 200 mg/m² given intravenously every 6 weeks. This amount may be administered as a single dose or divided into daily infusions of 75 to 100 mg/m² on two consecutive days. The dosage regimen will also depend on whether Carmustina medac is administered together with other anticancer medicines.

Doses will be adjusted according to your response to treatment.

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

Blood counts will be monitored frequently to avoid bone marrow toxicity, and the dose will be adjusted if necessary.

Route of administration

After reconstitution and dilution, Carmustina medac is administered intravenously by infusion (intravenous drip), protected from light, over a period of one to two hours. The infusion duration 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.

If you use more Carmustina medac than you should

Since the 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 have received.

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

4. Possible adverse effects

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

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

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

Carmustine medac 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), which may increase the risk of infections if white blood cells are reduced
• Ataxia (lack of voluntary coordination of muscle movements)
• Dizziness
• Headaches
• Transient redness of the eyes, blurred vision due to retinal hemorrhage
• Hypotension (low blood pressure)
• Phlebitis (inflammation of the veins) associated with pain, swelling, redness, sensitivity
• Respiratory disorders (related to the lungs) with breathing problems. This medicine can cause severe (possibly fatal) lung damage. Lung damage 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/tiredness
• Severe nausea and vomiting
• 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 up to 1 in 10 people)

• Acute leukemias and myelodysplasias (abnormal bone marrow development) following prolonged use. Some of the symptoms include bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps caused by swelling of lymph nodes in and around the neck, armpits, abdomen or groin, pallor, difficulty breathing, weakness, fatigue, or general decrease in energy.
• Anemia (reduction in the number of red blood cells in the blood)
• Encephalopathy (brain disorder). This may include symptoms such as muscle weakness in an area, reduced ability to make decisions or concentrate, involuntary contractions, tremors, difficulty speaking or swallowing, seizures
• Anorexia
• Constipation
• Diarrhea
• Inflammation of the mouth and lips
• Reversible hepatic toxicity with high-dose treatment. This may cause an increase in liver enzymes and bilirubin (detected by blood tests)
• Alopecia (hair loss)
• Skin flushing
• Reactions at the injection site

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

• Veno-occlusive disease (progressive blockage of veins), in which very small (microscopic) veins in the liver become blocked. Symptoms may include fluid accumulation in the abdomen, enlargement of the spleen, severe bleeding from the esophagus, yellowing of the skin and whites of the eyes.
• Breathing problems caused by interstitial fibrosis (with lower doses)
• Kidney problems
• Gynecomastia (enlargement of the breasts in males)

Frequency not known (cannot be estimated from available data)

• Muscle pain
• Seizures, including status epilepticus
• Tissue damage due to leakage at the injection site
• Any signs of infection
• Infertility
• It has been shown that carmustine negatively affects fetal development.
• Electrolyte abnormalities (and disturbances in electrolyte balance) (low blood levels of potassium, magnesium, and phosphate)

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Carmustina medac

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

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 the carton following EXP. The expiry date refers to the last day of the month indicated.

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

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

After reconstitution and dilution

After reconstitution, Carmustina medac is stable for 3 hours when stored in a glass container and protected from light.

The solution must be administered within 3 hours of reconstitution and dilution of the product. The solution must remain protected from light until the end of administration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Carmustina medac

• The active substance is carmustine.
• Each vial of powder for concentrate for solution for infusion contains 100 mg of carmustine.
• After reconstitution and dilution, one ml of solution contains 3.3 mg of carmustine.
• Excipients:
• Powder: contains no excipients.
• Solvent: anhydrous ethanol.

Appearance of the product and contents of the pack

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

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

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

One pack of Carmustina medac contains one vial with 100 mg of powder and one ampoule with 3 ml of solvent.

Marketing Authorization Holder and Manufacturer

medac

Gesellschaft für klinische Spezialpräparate mbH

Theaterstr. 6

22880 Wedel

Germany

Telephone: +49 4103 8006-0

Fax: +49 4103 8006-100

e-mail: [email protected]

Date of the most recent review of this summary: 08/2024

Other sources of information

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

This information is intended for healthcare professionals only:

This information is a brief description of the preparation and/or handling, incompatibilities, dosage, overdose, or monitoring measures and additional laboratory tests based on the current summary of product characteristics.

The powder for concentrate for solution for infusion of Carmustina medac contains no preservatives and is not intended for multi-dose use. Reconstitution and subsequent dilutions must be carried out under aseptic conditions.

If the recommended storage conditions are observed, degradation of the unopened vial can be avoided until the expiry date indicated on the packaging.

The lyophilized product contains no preservatives and is suitable for single use only. The lyophilisate may appear as a fine powder, but handling may cause it to appear as a heavier, clumped lyophilisate rather than a free-flowing powder due to the mechanical instability of the lyophilized suspension. The presence of an oily film may indicate melting of the medicinal product. These products are not suitable for use due to the risk of temperature deviations exceeding 30 °C. Such medicinal products must not be used. If there is any doubt about whether the product has been properly refrigerated, each vial in the pack should be inspected immediately. For inspection, hold the vial up to 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 sterile, refrigerated ethanol solvent supplied in the primary packaging (brown glass vial). Carmustine must be completely dissolved in ethanol before adding sterile water for injection. Then, aseptically add 27 ml of sterile water for injection to the alcoholic solution. The resulting 30 ml stock solution should be mixed thoroughly. When reconstituted according to recommendations, a clear, colorless or light yellow solution is obtained.

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

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

pH 4.0 to 5.0 and 385–397 mOsm/l (when diluted in 50 mg/ml [5 %] glucose injection solution), and

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

Method of administration

The reconstituted and diluted solution (i.e., the ready-to-use solution) must be administered intravenously by intravenous infusion over a period of one to two hours; administration must be completed within 3 hours of reconstitution/dilution of the medicinal product. The infusion should be administered using a PVC-free polyethylene (PE) infusion set. During administration, the container must be made of suitable glass. Additionally, ready-to-use solutions must be protected from light (e.g., by wrapping the container in aluminum foil) and preferably stored at temperatures below 20–22 °C, as carmustine degrades more rapidly at higher temperatures.

The infusion of Carmustina medac should be administered using a PVC-free PE infusion set.

Shorter infusion periods of Carmustina medac may cause severe pain and burning at the injection site. The injection site should be monitored during administration.

Standard guidelines for the safe handling and disposal of antineoplastic agents must be followed.

Dosage and additional laboratory tests

Initial doses

The recommended dose of Carmustina medac as monotherapy in previously untreated patients is 150 to 200 mg/m² administered intravenously every 6 weeks. This dose may be given as a single dose or divided into daily infusions of 75 to 100 mg/m² on two consecutive days.

When Carmustina medac is used in combination with other myelosuppressive agents or in patients with depleted bone marrow reserve, doses should be adjusted according to the patient's hematological profile, as shown below.

Monitoring and subsequent doses

A new cycle of Carmustina medac must not be administered until circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm³, white blood cells above 4,000/mm³), which typically occurs after six weeks. Blood counts should be monitored frequently, and repeated cycles must not be administered earlier than six weeks apart due to delayed hematological toxicity.

Subsequent doses following the initial dose should be adjusted based on the patient's hematological response to the previous dose, whether used as monotherapy or in combination with other myelosuppressive agents. The following scheme is recommended as a guide for dose adjustment:

In cases where the nadir of leukocytes and platelets after the initial dose does not fall within the same row (e.g., leukocytes > 4,000 and platelets < 25,000), the value corresponding to the lower percentage of the previous dose should be used (e.g., if the platelet count is < 25,000, a maximum of 50% of the previous dose should be administered).

There are no limits regarding the duration of carmustine treatment. If the tumor remains incurable or if severe or intolerable adverse reactions occur, carmustine treatment should be discontinued.

Conditioning treatment prior to HSCT

In patients with malignant hematological disorders, carmustine is administered intravenously in combination with other chemotherapeutic agents at a dose of 300–600 mg/m² prior to HSCT.

Special populations

Pediatric population

Carmustine must not be used in children under 18 years of age for safety reasons.

Elderly patients

In general, dose selection for elderly patients should be cautious, usually starting at the lower end of the dosing range, reflecting the greater frequency of impaired hepatic, renal, or cardiac function, concomitant diseases, or treatment with other medicinal products. Since elderly patients are more likely to have decreased renal function, care should be taken when selecting the dose, glomerular filtration should be monitored, and the dose adjusted accordingly.

Renal impairment

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

Compatibility/incompatibility with containers

The intravenous solution is unstable in polyvinyl chloride (PVC) containers. All plastics coming into contact with the carmustine infusion solution (e.g., infusion sets, etc.) must be made of non-PVC polyethylene; otherwise, glass containers should be used.