Carmustine Dr. Reddy's 100 mg powder and solvent for concentrate for solution for infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Carmustine Dr. Reddy's 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 questions, ask your doctor, pharmacist or nurse.
• If you get any side effects, talk to your doctor or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Carmustine Dr. Reddy's is and what it is used for

Carmustine Dr. Reddy's is a medicine that contains 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 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, meduloblastoma, astrocytoma, and ependymoma), brain metastases
• Multiple myeloma (a malignant tumor developing in the bone marrow)
• Hodgkin’s lymphoma (malignant enlargement of lymph nodes)
• Non-Hodgkin’s lymphoma (malignant enlargement of 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 capable of forming 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 starting to use Carmustine Dr. Reddy's

Do not use Carmustine Dr. Reddy's:

• if you are allergic to carmustine or to any of the other components of this medicine (listed in section 6);
• if you have suppression of blood cell formation in the bone marrow, resulting in low numbers of platelets, white blood cells (leukocytes), 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 Carmustine Dr. Reddy's.

The main adverse effect of this medicine is delayed bone marrow suppression, which may present as fatigue, skin and mucosal bleeding, infections, and fever due to blood abnormalities. Therefore, your doctor will monitor your blood counts weekly for at least 6 weeks after each dose. According to the recommended dosage, cycles of Carmustine Dr. Reddy's will not be administered more frequently 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 carmustine 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 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 blood levels of potassium, magnesium, and phosphate).

Abdominal pain (neutropenic enterocolitis) may occur as an adverse reaction related to therapy following treatment with chemotherapeutic agents.

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

Children and adolescents

Carmustine Dr. Reddy's must not be used in children and adolescents under 18 years of age.

Other medicines and Carmustine Dr. Reddy's

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.

Carmustine Dr. Reddy's 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 become pregnant, consult your doctor or pharmacist before using this medicine.

Pregnancy and fertility

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

Male patients should use adequate contraceptive methods during treatment with Carmustine Dr. Reddy's 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. A risk to newborns/infants cannot be excluded.

Driving and Use of Machinery

The influence of carmustine on the ability to drive and use machinery is none or negligible. 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 machinery.

Carmustine Dr. Reddy's contains ethanol (alcohol)

This medicine contains 2.4 g of alcohol (ethanol) per vial, equivalent to 25.92 g per maximum dose (10 % v/v). The amount of alcohol 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 addicted to alcohol, consult your doctor or pharmacist before taking this medicine.

3. How to use Carmustine Dr. Reddy's

Carmustine Dr. Reddy's 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 intervals of at least 6 weeks. The recommended dose of Carmustine Dr. Reddy's as monotherapy in previously untreated patients is 150 to 200 mg/m² administered intravenously every 6 weeks. This amount may be given as a single dose or divided into daily infusions of 75 to 100 mg/m² on two consecutive days. The dosage will also depend on whether Carmustine Dr. Reddy's is administered in combination with other anticancer medications.

Dosage will be adjusted according to the patient's response to treatment.

The recommended dose of Carmustine Dr. Reddy's when administered in combination with other chemotherapeutic agents prior to hematopoietic progenitor cell transplantation is 300–600 mg/m² by intravenous route.

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, Carmustine Dr. Reddy's is administered intravenously by infusion over a period of one to two hours, protected from light. 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 Carmustine Dr. Reddy's than you should

Since this medicine will be administered by your doctor or nurse, it is unlikely that you will receive an incorrect dose. However, if you have any doubts about the amount of medicine you have received, inform your doctor or nurse immediately.

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

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 will experience them.

Inform 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 Dr. Reddy's may cause the following adverse effects:

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

• Delayed myelosuppression (reduction in blood cells produced 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 reddening of the eyes, blurred vision due to retinal haemorrhage
• Hypotension (low blood pressure)
• Phlebitis (inflammation of the veins) associated with pain, swelling, redness, and tenderness
• Respiratory disorders (lung-related) with breathing difficulties

This medicine may cause severe (possibly fatal) lung damage. Lung injury may occur 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 leukaemias and bone marrow dysplasias (abnormal bone marrow development) after prolonged use. Some symptoms include bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps caused by swollen lymph nodes in and around the neck, armpits, abdomen or groin, paleness, difficulty breathing, weakness, fatigue, or general loss of energy.
• Anaemia (reduction in the number of red blood cells in the blood)
• Encephalopathy (brain disorder). Symptoms may include muscle weakness in one area, reduced ability to make decisions or concentrate, involuntary contractions, tremors, difficulty speaking or swallowing, seizures
• Anorexia
• Constipation
• Diarrhoea
• Inflammation of the mouth and lips
• Reversible liver toxicity with high-dose treatment. This may lead to increased 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 oesophagus, yellowing of the skin and whites of the eyes.
• Respiratory problems caused by interstitial fibrosis (with lower doses)
• Kidney problems
• Gynaecomastia (enlargement of the breasts in males)

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

• Muscle pain
• Seizures, including status epilepticus
• Tissue damage due to leakage at the injection site
• Any sign of infection
• Infertility
• Carmustine has been shown to have harmful effects on fetal development.
• Electrolyte abnormalities (and disturbances in electrolyte balance, such as low blood levels of potassium, magnesium, and phosphate)

Reporting of adverse effects

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

5. Storage of Carmustine Dr. Reddy's

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

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

After reconstitution and dilution

After reconstitution, Carmustine Dr. Reddy's 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 after 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, followed by an additional 3 hours at room temperature, protected from light.

Medicines should 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 container and additional information

Composition of Carmustine Dr. Reddy's

• 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 Package

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 clear, colourless liquid supplied in a transparent glass ampoule.

One pack of Carmustine Dr. Reddys contains one vial with 100 mg of powder and one 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:

Member State	Medicinal product name
Spain	Carmustina Dr. Reddys 100 mg powder and solvent for concentrate for solution for infusion EFG
Malta	Carmustine Dr. Reddy’s 100 mg powder and solvent for concentrate for solution for infusion

Date of the most recent review of this leaflet: May 2024

Detailed information about this medicinal product is available on the website of the Spanish Agency of Medicinal Products and Medical Devices (AEMPS): http://www.aemps.gob.es/.

---

This information is intended for healthcare professionals only:

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

Carmustine Dr. Reddy's powder for concentrate for solution for infusion does not contain preservatives and is not designed as a multi-dose vial. Reconstitution and subsequent dilutions must be performed under aseptic conditions.

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

Vials of Carmustine Dr. Reddy's powder for solution for infusion must 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 an indication of carmustine decomposition, an oily film appears at the bottom of the vial. Such vials must no longer be used.

The lyophilized (dry) dosage form does not contain preservatives. 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 refrigerated sterile 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 must be thoroughly mixed. Reconstitution according to these recommendations yields a clear, colorless or pale yellow stock solution.

The 30 ml stock solution must be immediately diluted 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) must be mixed for at least 10 seconds prior to 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 an additional 3 hours protected from light.

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

pH 4.0 to 6.8 and 365–395 mOsm/kg (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 as an 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 must be administered using a PVC-free polyethylene (PE) infusion set.

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

The infusion must be administered using a PVC-free polyethylene (PE) infusion set.

Infusion of Carmustine Dr. Reddy's over shorter periods may cause intense pain and burning at the injection site. The injection site must be monitored during administration.

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

Dosage and complementary laboratory tests

Initial doses

The recommended dose of Carmustine Dr. Reddy's 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 Carmustine Dr. Reddy's is used in combination with other myelosuppressive medicinal products 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 Carmustine Dr. Reddy's must not be administered until circulating blood elements have recovered to acceptable levels (platelets above 100,000/mm³, leukocytes above 4,000/mm³), which generally occurs after six weeks. Blood counts must be monitored frequently, and repeated cycles must not be administered before six weeks 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, both in monotherapy and in combination with other myelosuppressive medicinal products. The following scheme is suggested as a guide for dose adjustment:

Nadir after previous dose	Percentage of previous dose to administer
Leukocytes/mm3	Platelets/mm3
>4,000	>100,000	100%
3,000 – 3,999	75,000 – 99,999	100%
2,000 – 2,999	25,000 – 74,999	70%
<2,000	<25,000	50%

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 medications. 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 should be adjusted accordingly.

Renal impairment

In patients with renal impairment, the dose of Carmustine Dr. Reddys should be reduced if glomerular filtration rate 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.