CARMUSTINE Dr. Reddy's 100 mg Powder and Solvent for Concentrate for Infusion Solution

Introduction

Package Leaflet: Information for the User

Carmustine Dr. Reddys 100 mg powder and solvent for concentrate for solution for infusion EFG

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, talk to your doctor or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Carmustine Dr. Reddys and what is it used for

Carmustine Dr. Reddys is a medicine that contains carmustine. Carmustine belongs to a group of anticancer medicines, known as nitrosoureas, which work by slowing down the growth of cancer cells.

Carmustine is indicated in adults for 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, medulloblastoma, astrocytoma, and ependymoma), brain metastases
• Multple myeloma (a malignant tumor that develops in the bone marrow)
• Hodgkin's lymphoma (malignant thickening of the lymph nodes)
• Non-Hodgkin's lymphoma (malignant thickening of the lymph nodes)
• Gastrointestinal tract tumors
• Malignant melanoma (skin cancer)

Carmustine is also used as a conditioning treatment prior to autologous stem cell transplantation (a procedure in which a person receives blood stem cells that form any type of blood cell) for malignant diseases of the lymphatic system (Hodgkin's lymphoma and non-Hodgkin's lymphoma).

2. What you need to know before you use Carmustine Dr. Reddys

Do not use Carmustine Dr. Reddys:

• if you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 6);
• if you have bone marrow suppression and, therefore, have a reduced number of platelets, white blood cells (leukocytes), or red blood cells (erythrocytes), either as a result of chemotherapy or for other reasons;
• if you have severe kidney failure;
• in children and adolescents;
• if you are breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Carmustine Dr. Reddys.

The main side effect of this medicine is delayed bone marrow suppression, which can manifest as fatigue, bleeding from the skin and mucous membranes, infections, and fever as a result of changes in the blood. Therefore, your doctor will check your blood counts every week for at least 6 weeks after each dose. Following the recommended dosage, Carmustine Dr. Reddys cycles will not be administered more frequently 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 lung function tests will be performed before starting treatment (see also the 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 levels of potassium, magnesium, and phosphate in the blood).

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

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

Carmustine Dr. Reddys should not be used in children and adolescents under 18 years of age.

Other medicines and Carmustine Dr. Reddys

Tell your doctor or pharmacist if you are taking, have recently taken, or might 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, an anticancer medicine.

Carmustine Dr. Reddys with 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 have a baby, ask your doctor or pharmacist for advice before using this medicine.

Pregnancy and fertility

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 are advised to use effective contraceptive methods to avoid becoming pregnant during treatment with this medicine and for at least six months after the end of treatment.

Male patients should use adequate contraceptive methods during treatment with Carmustine Dr. Reddys and for at least 6 months after the end of treatment to avoid getting their partners pregnant.

Breastfeeding

Do not breastfeed while you are taking this medicine and for 7 days after treatment. The risk to newborns/infants cannot be excluded.

Driving and using machines

Carmustine has no or negligible influence on the ability to drive and use machines. You should talk to your doctor before driving or using tools or machines, as the amount of alcohol contained in this medicine may affect your ability to drive or use machines.

Carmustine Dr. Reddys 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% v/v). 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 use machinery, as it may affect your judgment and reaction speed.

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

The amount of alcohol in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.

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

If you have an alcohol addiction, talk to your doctor or pharmacist before taking this medicine.

3. How to use Carmustine Dr. Reddys

Carmustine Dr. Reddys will always be administered by a healthcare professional with experience 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 Carmustine Dr. Reddys as monotherapy in previously untreated patients is 150 to 200 mg/m2 by intravenous infusion every 6 weeks. This dose may be administered as a single dose or divided into daily infusions of 75 to 100 mg/m2 over two consecutive days. The dosage will also depend on whether Carmustine Dr. Reddys is administered with other anticancer medicines.

The doses will be adjusted according to your response to treatment.

The recommended dose of Carmustine Dr. Reddys administered in combination with other chemotherapeutic agents before stem cell transplantation is 300-600 mg/m2 by intravenous infusion.

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

Method of administration

After reconstitution and dilution, Carmustine Dr. Reddys is administered intravenously by infusion, 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 your doctor and may vary for each patient.

If you use more Carmustine Dr. Reddys than you should

Since it will be your doctor or nurse who administers this medicine to you, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any doubts about the amount of medicine you have received.

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount ingested.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell 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 whole body) and feeling of fainting. These may be signs of a severe allergic reaction.

Carmustine Dr. Reddys may cause the following side effects:

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

• Delayed bone marrow suppression (decrease in blood cells in the bone marrow) which can increase the risk of infections if white blood cells are reduced
• Ataxia (lack of voluntary muscle coordination)
• Dizziness
• Headaches
• Transient eye redness, 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 may cause severe lung damage (possibly fatal). Lung damage may occur years after treatment. Tell 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, skin inflammation (dermatitis)
• Accidental contact with the skin may cause transient hyperpigmentation (darkening of a skin or nail area)

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 of the symptoms are gum bleeding, bone pain, fever, frequent infections, frequent or severe nosebleeds, swelling caused by lymph node swelling in and around the neck, armpits, abdomen, or groin, paleness, 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 of muscle weakness in one area, decreased ability to make decisions or concentrate, involuntary contractions, tremors, difficulty speaking or swallowing, seizures;
• Anorexia
• Constipation
• Diarrhea
• Mouth and lip inflammation
• Reversible liver toxicity with high-dose treatment. This may cause an increase in liver enzymes and bilirubin (detected by blood tests)
• Alopecia (hair loss)
• Redness of the skin
• Reactions at the injection site

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

• Venous occlusive disease (progressive blockage of small veins) in the liver, which may include symptoms of: fluid accumulation in the abdomen, liver enlargement, severe bleeding from the esophagus, yellowing of the skin and the whites of the eyes.
• Respiratory problems caused by interstitial fibrosis (with lower doses)
• Kidney problems
• Gynecomastia (breast growth in males)

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

• Muscle pain
• Seizures (crises), including status epilepticus
• Tissue damage due to leakage at the injection site
• Any sign of infection
• Infertility
• Carmustine has been shown to have a negative effect on fetal development.
• Electrolyte imbalances (and alterations of electrolyte balance (low levels of potassium, magnesium, and phosphate in the blood))

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Information System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Carmustine Dr. Reddys

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 which is stated on the label and carton after EXP. The expiry date is the last day of the month stated.

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

After reconstitution and dilution

After reconstitution, Carmustine Dr. Reddys is stable for 3 hours when stored in a glass container and protected from light.

The ready-to-use solution should be administered within 3 hours of reconstitution and dilution of the product and should be protected from light until the end of administration.

The ready-to-use infusion solution is stable at room temperature, protected from light for 3 hours, in the refrigerator (2°C - 8°C) for 24 hours, and then at room temperature for 3 hours more, protected from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Carmustine Dr. Reddys

• The active substance 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 Package Contents

Carmustina Dr. Reddys is a powder and solvent for concentrate for solution for infusion.

The powder is a white or almost white powder supplied in a brown glass vial.

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

A package of Carmustina Dr. Reddys contains a vial with 100 mg of powder and an ampoule with 3 ml of solvent.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Reddy Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona

(Spain)

Manufacturer

betapharm Arzneimittel GmbH

Kobelweg 95

86156 Augsburg

Germany

or

Pharmadox Healthcare Ltd., KW20A Kordin

Industrial Park, Paola PLA 3000, Malta

or

Rual Laboratories S.R.L., Building H, 1st

Floor, Sector 3, Splaiul Unirii 313, Bucharest,

030138, Romania

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

Date of Last Revision of this Leaflet:May 2024

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

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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 of the medicinal product, overdose or monitoring measures and laboratory tests based on the current summary of product characteristics.

The powder of Carmustina Dr. Reddys for concentrate for solution for infusion does not contain preservatives and is not designed as a multi-dose vial. Reconstitution and subsequent dilutions should be performed under aseptic conditions.

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

The vials of Carmustina Dr. Reddys powder for solution for infusion should be transported and stored between 2 °C and 8 °C (see also section 6.4). Storage of carmustine at temperatures above 27 °C leads to liquefaction of the substance, as carmustine has a low melting point. As a sign of carmustine degradation, an oily film appears at the bottom of the vial. Such vials can no longer be used.

The lyophilized (dry) dosage form does not contain preservatives. The containers are not intended for repeated withdrawals.

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 sterile refrigerated ethanol solvent supplied in the primary packaging (brown glass vial). Carmustine should be completely dissolved in ethanol before adding sterile water for injectable preparations. Then, add 27 ml of sterile water for injectable preparations to the alcohol solution in a sterile manner. The 30 ml parent solution should be mixed well. Reconstitution, following the recommendations, results in a clear, colorless or pale yellow parent solution.

The 30 ml parent solution should be diluted immediately by adding 30 ml of parent solution to 500 ml of glucose 50 mg/ml (5%) injectable solution or to 500 ml of sodium chloride 9 mg/ml (0.9%) injectable solution 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.

The ready-to-use infusion solution is stable at room temperature, protected from light, for 3 hours, in the refrigerator (between 2 °C and 8 °C) for 24 hours, and then at room temperature for another 3 hours, protected from light.

pH 4.0 to 6.0 and 355-375 mOsm/kg (if diluted in glucose 50 mg/ml [5%] injectable solution), and

pH 4.0 to 6.8 and 365-395 mOsm/kg (if diluted in sodium chloride 9 mg/ml [0.9%] injectable solution)

Method of Administration

The reconstituted and diluted solution (i.e., the ready-to-use solution) should be administered intravenously by drip infusion over a period of one to two hours; administration should be completed within 3 hours of reconstitution/dilution of the medicinal product. The infusion should be administered with a PVC-free PE infusion set.

During administration of the medicinal product, the container should be made of suitable glass. Additionally, the ready-to-use solutions should be protected from light (e.g., by wrapping the ready-to-use solution container with aluminum foil) and stored preferably at temperatures below 20-22 °C, as carmustine degrades more rapidly at higher temperatures.

The infusion should be administered with a PVC-free PE infusion set.

Infusion of Carmustina Dr. Reddys over shorter periods may produce intense pain and burning at the injection site. The injection site should be monitored during administration.

The guidelines for the correct handling and disposal of antineoplastics should be followed.

Dosage and Laboratory Tests

Initial Doses

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

When Carmustina Dr. Reddys is used in combination with other myelosuppressive agents or in patients in whom the bone marrow reserve is depleted, the doses should be adjusted based on the patient's hematologic profile, as shown below.

Monitoring and Subsequent Doses

A new cycle of Carmustina Dr. Reddys should not be administered until the circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm3, leukocytes above 4,000/mm3), and this usually occurs in six weeks. Blood counts should be monitored frequently, and repeat cycles should not be administered before six weeks due to delayed hematologic toxicity.

Subsequent doses to the initial dose should be adjusted based on the patient's hematologic response to the previous dose, both as monotherapy and in combination with other myelosuppressive agents. The following scheme is suggested as a guide for dose adjustment:

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 lower 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 to the treatment period with carmustine. In case the tumor remains incurable or severe or intolerable adverse reactions appear, treatment with carmustine should be discontinued.

Pre-TCHP Conditioning Treatment

In patients with malignant hematological disorders, before TCHP, carmustine is administered in combination with other chemotherapeutic agents at a dose of 300-600 mg/m2 intravenously.

Special Populations

Pediatric Population

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

Elderly Patients

In general, the dose for an elderly patient should be selected with caution, usually starting at the lower end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. Since elderly patients are more likely to have decreased renal function, dose selection should be cautious, and glomerular filtration should be monitored, and the dose reduced based on this.

Renal Impairment

In patients with renal impairment, the dose of Carmustina Dr. Reddys should be reduced if glomerular filtration is decreased.

Compatibility/Incompatibility with Containers

The intravenous solution is unstable in polyvinyl chloride containers. All plastics that come into contact with the carmustine infusion solution (e.g., infusion set, etc.) should be PVC-free PE; otherwise, glass containers should be used.