Prospecto: information for the user

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

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

• Keep this prospect, as you may have 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.

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

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

Carmustin 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 lymphoma and non-Hodgkin lymphoma).

No use Carmustina Dr. Reddys:

Advertencias y precauciones

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

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 due to 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 Dr. Reddys cycles will not be administered at a frequency greater than every 6 weeks. The dosage will be confirmed with a blood count.

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

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

High-dose carmustine (up to 600 mg/m2) treatment 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 imbalance (low blood levels of potassium, magnesium, and phosphate).

Neutropenic enterocolitis (abdominal pain) may occur as a treatment-related adverse reaction after 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).

Niños y adolescentes

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

Otros medicamentos y Carmustina Dr. Reddys

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.

Carmustina Dr. Reddys con alcohol

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

Embarazo, lactancia y fertilidad

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

Embarazo y fertilidad

Carmustine should not be used during pregnancy because it may harm the fetus. Therefore, this medication should not be administered to pregnant women normally. If 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 medication and for at least six months after completing treatment.

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

Lactancia

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

Conducción y uso de máquinas

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

Carmustina Dr. Reddys contiene etanol (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 use 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 Dr. Reddys 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 dosage of Carmustina Dr. Reddys 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 two consecutive days. Dosage will also depend on whether Carmustina Dr. Reddys is administered with other cancer medications.

Doses will be adjusted based on your response to treatment.

The recommended dosage of Carmustina Dr. Reddys administered in combination with other chemotherapeutic agents before a hematopoietic stem cell transplant is 300-600 mg/m² by intravenous route.

Regular 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 Dr. Reddys is administered intravenously through a drip (intravenous), protected from light, over a period of one to two hours. The duration of the infusion should not be less than one 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 Take More Carmustina Dr. Reddys 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.

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 medication and the amount ingested.

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. They may be signs of a severe allergic reaction.

Carmustine Dr. Reddy's 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 coordination of muscle movements)
• Dizziness
• Headaches
• Transient conjunctival redness, blurred vision due to retinal hemorrhage
• Hypotension (low blood pressure)
• Phlebitis (inflammation of 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 or fatigue

• Severe nausea and vomiting
• When used on the skin, inflammation of the skin (dermatitis)
• Accidental contact with the skin may cause transient hyperpigmentation (darkening of a skin area or nails)

Frequent(may affect up to 1 in 10 people)

• Leukemias and bone marrow dysplasias (abnormal development of 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 red blood cells in the blood)
• Cerebral encephalopathy (brain disorder). It may include symptoms ofmuscle weaknessin a region, decreased ability to make decisions orconcentration,involuntary contractions, tremors, difficultyspeakingorswallowing,seizures;
• Anorexia
• Constipation
• Dyspepsia
• Diarrhea
• Oral 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)
• Skin rubefaction
• Reactions at the injection site

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

• Thrombophlebitis (obstruction of small veins in the liver). It may include symptoms of: fluid accumulation in the abdomen, enlarged spleen, severe esophageal bleeding, 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)

Unknown frequency(cannot be estimated from available data)

• Muscle pain
• Seizures (crisis), including status epilepticus
• Tissue damage due to leakage 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 effect, consult your doctor or pharmacist, even if it is not listed in this leaflet. 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.

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

After reconstitution and dilution

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

The ready-to-use solution must be administered within 3 hours following reconstitution and dilution of the product and must 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 an additional 3 hours, protected from light.

Medications 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. This will help protect the environment.

Composition of Carmustine Dr. Reddys

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.

Appearance of the product and contents of the pack

Carmustine 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 transparent, colourless liquid supplied in a transparent glass ampoule.

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

Holder of the marketing authorisation and responsible for manufacturing

Holder of the marketing authorisation

Reddy Pharma Iberia, S.A.

Avda. Josep Tarradellas nº 38

08029 Barcelona

(Spain)

Responsible for manufacturing

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 authorised in the Member States of the European Economic Area with the following names:

Date of the last review of this leaflet:May 2024

The detailed information on this medicinal product 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 solely for healthcare professionals:

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

The powder for concentrate for solution for infusion of Carmustine Dr. Reddys 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 expiry date indicated on the packaging.

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

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

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 should be dissolved completely in ethanol before adding sterile water for injection preparations. Subsequently, add sterile water for injection preparations in a manner that is sterile, 27 ml to the alcoholic solution. The 30 ml mother solution should be mixed well. The reconstitution, following the recommendations, results in a transparent, colourless or yellowish mother solution.

The 30 ml mother solution should 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) should be mixed for at least 10 seconds before administration.

The ready-to-use solution for infusion is stable at room temperature protected from light for 3 hours, in the refrigerator (between 2 °C and 8 °C) for 24 hours and, subsequently, 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 injection solution 50 mg/ml [5%]), and

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

Administration form

The reconstituted and diluted solution (i.e. the ready-to-use solution) should be administered by intravenous infusion via a PE infusion set without PVC over a period of one to two hours; the administration should be completed within three hours after reconstitution/dilution of the medicinal product. The infusion should be administered with a PE infusion set without PVC.

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

The infusion should be administered with a PE infusion set without PVC.

The infusion of Carmustine Dr. Reddys 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 Dr. Reddys in monotherapy in previously untreated patients is 150 to 200 mg/m2by intravenous infusion every 6 weeks. This amount can be administered in a single dose or divided into daily infusions of 75 to 100 mg/m2over two consecutive days.

Carmustine Dr. Reddys should be used in combination with other myelosuppressive medicinal products or in patients in whom the bone marrow reserve is exhausted, the doses should be adjusted according to the patient's haematological profile, as shown below.

Monitoring and subsequent doses

No new cycle of Carmustine Dr. Reddys should be administered until the circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm3, leucocytes 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 haematological toxicity.

Subsequent doses after the initial dose should be adjusted according to the patient's haematological response to the previous dose, both in monotherapy and in combination with other myelosuppressive medicinal products. The following scheme is suggested as a guide for adjusting the dose:

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

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

Pre-conditioning treatment prior to TCHP

In patients with malignant haematological disorders, carmustine is administered in combination with other chemotherapy agents in a dose of 300-600 mg/m2by intravenous infusion before TCHP.

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 deterioration of hepatic, renal or cardiac function, and concomitant diseases or treatment with other medicinal products. Since elderly patients are more likely to have a decrease in 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 Dr. Reddys 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 set, etc.) must be made of polyethylene without PVC; otherwise, glass containers should be used.