Prospect: information for the user

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

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• If you experience adverse effects, consult your doctor or nurse, even if they are not listed in this prospect. See section 4.

Content of the prospect

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

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

Do not use Carmustina Glenmark

Warnings and precautions

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

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

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

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

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

It may cause stomach pain (neutropenic enterocolitis) as an adverse event related to chemotherapy therapy.

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).

Be especially careful when using Carmustina Glenmark

The benefit-risk balance of carmustine should be carefully weighed, as with other antitumor agents.

Carmustina may have a detrimental effect on genetic material. Male patients treated with carmustine will be advised to use effective contraceptive methods during treatment and for at least 6 months after completing treatment, as well as to request information on sperm preservation before treatment due to the possibility of permanent infertility (irreversible) caused by carmustine treatment.

Women should not become pregnant during carmustine treatment.

Carmustina should not be administered to patients with reduced platelet counts (thrombocytopenia), white blood cell counts (leucopenia), or red blood cell counts (anemia), either due to chemotherapy treatment or for other reasons.

In patients whose bone marrow reserve is depleted due to disease or previous treatments, an increase in adverse reactions such as reduced white blood cell and platelet counts (leucopenia or thrombocytopenia) can be expected.

The injection site should be closely monitored during perfusion due to the risk of extravasation (loss of perfusion solution from the vein to the surrounding tissues).

Your doctor will discuss the possibility of allergic reactions and their symptoms with you. You should contact your doctor immediately if these symptoms appear (see section “Possible side effects”).

Patients with severe underlying diseases and advanced stages of the disease have a higher risk of experiencing adverse effects. This is especially important in elderly patients.

Special instructions before starting treatment

Patients should be warned of the symptoms of reduced white blood cell counts (fever with granulocytopenia) or reduced platelet counts (skin petechiae and other bleeding with thrombocytopenia). You should see your doctor if these effects occur.

Prior to starting carmustine treatment, patients should be warned of possible gastrointestinal disturbances such as nausea or vomiting.

Patients should be warned of possible lung damage and allergic reactions and their symptoms. You should see your doctor if these effects occur.

Children and adolescents

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

Other medicines and Carmustina Glenmark

Inform your doctor if you are taking, have taken recently, or may need to take any other medicine, including those purchased without a prescription, such as:

• Phenytoin, 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.
• Melphalan, a cancer medicine.

It may be expected that there will be an increase in adverse reactions such as reduced platelet or white blood cell counts (thrombocytopenia and leucopenia) when combined with other myelosuppressive medicines (medicines that suppress the formation of blood cells in the bone marrow) such as vincristine, methotrexate, cyclophosphamide, procarbazine, chlorambucil (nitrogen mustard), fluorouracil, vinblastine, actinomycin (dactinomycin), bleomycin, doxorubicin (adriamycin).

The myelosuppressive effect of carmustine may be increased by cimetidine (medicine used for excessive stomach acid production).

It may be expected that there will be cross-resistance in concurrent treatment with other alkylating agents (cytostatic agents) such as chlorambucil and cyclophosphamide.

Use of Carmustina Glenmark with alcohol

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

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 medicine.

Pregnancy

Carmustine may cause genetic damage and harm the developing embryo/fetus.

Carmustine should not be used during pregnancy because it may harm the fetus.

Therefore, this medicine should not be administered to pregnant women. If it is used during pregnancy, the patient should be aware of the possible risk to the fetus. Women of childbearing age should use effective contraceptive methods to avoid becoming pregnant during treatment with this medicine and for at least 6 months after completing treatment.

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

Breastfeeding

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

Fertility

Carmustine may have a detrimental effect on genetic material. Male patients treated with carmustine should request information on sperm preservation before treatment due to the possibility of permanent infertility (irreversible) caused by carmustine treatment.

Driving and operating machinery

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

Carmustina Glenmark contains ethanol (alcohol)

This medicine 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 of this medicine (600 mg/m2in a 70 kg patient) 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 affect your judgment and reaction time.

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 or breastfeeding, consult your doctor or pharmacist before taking this medicine.

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

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

Adults

The 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 in monotherapy in previously untreated patients is 150 to 200 mg/m² by intravenous route every 6 weeks. This amount can be administered as a single dose or divided into daily infusions, 75 to 100 mg/m², over 2 consecutive days. The dosage will also depend on whether carmustina is administered with other cancer medications.

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

The recommended dose of carmustina administered in combination with other anticancer substances before hematopoietic stem cell transplantation is 300 to 600 mg/m² by intravenous route.

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 is administered intravenously through a drip (intravenous) over a period of 1 to 2 hours protected from light. The duration of the infusion should not be less than 1 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 your doctor and may vary for each patient.

If You Use More Carmustina Glenmark 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 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 feeling like you are going to faint. These may be signs of a severe allergic reaction.

Carmustine may cause the following side effects:

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

• Respiratory disorders (lung-related problems) with difficulty breathing;

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

Common(may affect up to 1 in 10 people)

• Acute leukemias and bone marrow dysplasias (abnormal development of the bone marrow). 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)
  • Cerebral encephalopathy (brain disorder). It may include symptoms of muscle weakness in a particular area, decreased ability to make decisions or concentration, involuntary contractions, tremors, difficulty speaking or swallowing, seizures;
  • 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)
  • Redness of the skin
  • Reactions at the injection site

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

Unknown frequency(cannot be estimated from available data)

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on 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).

After reconstitution and dilution

After reconstitution, Carmustina Glenmark is stable for 3 hours, when it is stored 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.

Medications should not be thrown down the drains or in the 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 Glenmark

• The active ingredient is carmustine.

Each vial of powder for concentrate for solution for infusion contains 100 mg of carmustine.

After reconstitution and dilution, one milliliter of solution contains 3.3 mg of carmustine.

• The other ingredients are:
• Powder: does not contain excipients
• Solvent: anhydrous ethanol

Appearance of the product and contents of the package

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

The powder is yellowish flakes or a solidified mass that is supplied in a type I amber glass vial of 30 ml closed with a 20 mm rubber stopper and sealed with a 20 mm aluminum cap with a polypropylene disc.

The solvent is a transparent, colorless, mobile, volatile liquid supplied in a type I transparent tubular glass vial of 5 ml closed with a 20 mm rubber stopper and sealed with a 20 mm aluminum cap with a polypropylene disc.

The package contains 1 vial with 100 mg of powder and 1 vial with 3 ml of solvent.

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

Pharmadox Healthcare Ltd

KW20A Kordin Industrial Park

Paola, PLA3000

Malta

You can request more information about this medication by contacting the local representative of the holder of the marketing authorization:

Viso Farmacéutica S.L.U.

c/ Retama 7, 7ª planta

28045 Madrid

This medication has been authorized in the member states of the European Economic Area with the following names:

GermanyCarmustin Glenmark 100 mg Powder and Solvent for the Preparation of a Concentrate for an Infusion Solution

SpainCarmustina Glenmark 100 mg powder and solvent for concentrate for solution for infusion EFG

Revision date of this leaflet:November 2024.

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es).

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This information is intended only for healthcare professionals:

This information is a brief description of the preparation and/or handling, incompatibilities, dosage of the medication, overdose or measures of vigilance and complementary laboratory explorations based on the current technical file.

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

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

The lyophilized product does not contain preservatives and is only suitable for single use. The lyophilized product may have the appearance of a fine powder, but handling may make it appear as a heavier and more lumpy lyophilized product instead of a powder due to the mechanical instability of the lyophilized agglomerate. The presence of an oily film may be an indication of the fusion of the medication.

These products are not valid for use due to the risk of temperature deviations greater than 30 °C. This medication 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 (amber glass vial). Carmustine should be completely dissolved in ethanol before adding sterile water for injectable preparations. Then, add sterile water for injectable preparations in an aseptic manner to the alcoholic solution. The resulting solution mother of 30 ml should be mixed well. Reconstitution, following the recommendations, results in a transparent, colorless to yellowish solution mother.

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

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

pH 4.0 to 5.0 and 385-397 mOsmol/l (if diluted in a 5% glucose injectable solution [50 mg/ml]) and pH 4.0 to 6.8 and 370-378 mOsmol/l (if diluted in a 0.9% sodium chloride injectable solution [9 mg/ml]).

Administration form

The reconstituted and diluted solution (i.e., the ready-to-use solution) should be administered intravenously via infusion over a period of one to two hours; administration should be completed within three hours after reconstitution/dilution of the medication. The infusion should be administered with a PE tubing without PVC. During administration of the medication, the container should be of suitable glass. In addition, the ready-to-use solutions should 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 should be administered with a PE tubing without PVC.

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

Proper handling and disposal of antineoplastics should be followed.

Dosage and complementary laboratory explorations

Initial doses

The recommended dose of carmustine 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/m2over two consecutive days.

When carmustine is used in combination with other myelosuppressive medications or in patients in whom the bone marrow reserve is exhausted, doses should be adjusted based on the patient's hematological profile, as shown below.

Vigilance and subsequent doses

No new cycle of carmustine 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 should be monitored frequently, and no repeated cycles should be administered before six weeks due to delayed hematological toxicity.

Subsequent doses after the initial dose should be adjusted based on the patient's hematological response to the previous dose, both in monotherapy and in combination with other myelosuppressive medications. 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 is not in the same row (e.g., leukocytes >4,000 and platelets <25,000), the value corresponding to the lowest percentage of the previous dose should be used (e.g., if the platelet value is <25,000, a maximum of 50% of the previous dose should be administered).

There are no limits for the duration of treatment with carmustine. 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

Carmustine is administered in combination with other chemotherapeutic agents in patients with malignant hematological diseases before TCHP at a dose of 300 mg/m2to 600 mg/m2intravenously.

Special populations

Pediatric population

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

Geriatric population

Generally, 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 deterioration of hepatic, renal, or cardiac function, and of concomitant diseases or treatment with other medications. Since elderly patients are more likely to have a decrease in renal function, care should be taken when selecting the dose, and renal filtration should be monitored and the dose reduced accordingly.

Renal insufficiency

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

Compatibility/Incompatibility with containers

The intravenous solution is unstable in PVC chloride containers. All plastics that come into contact with the carmustine infusion solution (e.g., infusion equipment, etc.) should be made of polypropylene, or else glass containers should be used.