Carmustine AccordPharma 300 mg powder and solvent for concentrate for infusion solution

Package leaflet: Information for the patient

Introduction

Package leaflet: information for the patient

Carmustine Accordpharma 50 mg powder and solvent for concentrate for solution for infusion

Carmustine Accordpharma 300 mg powder and solvent for concentrate for solution for infusion

Read the entire 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, consult your doctor, pharmacist, or nurse.
• If you experience any side effects, consult your doctor or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Carmustina Accordpharma 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 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
• Second-line treatment of non-Hodgkin lymphoma and Hodgkin's disease
• Tumors of the gastrointestinal tract or digestive tract
• Malignant melanoma (skin cancer)
• As conditioning treatment prior to autologous hematopoietic progenitor cell transplantation (HPC) in malignant hematological disorders (Hodgkin's disease / non-Hodgkin lymphoma)

2. What you need to know before using Carmustine Accordpharma

Do not use Carmustine Accordpharma

• 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 low levels 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 starting to use Carmustine Accordpharma.

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. Following the recommended dosage, cycles of Carmustine Accordpharma 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").

High-dose treatment with Carmustine Accordpharma (up to 600 mg/m²) is only performed in combination with subsequent stem cell transplantation. Such 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 therapy 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, you should contact your doctor immediately (see section 4).

Children and adolescents

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

Other medicines and Carmustine Accordpharma

Tell your doctor if you are taking, have recently taken, or might need to take any other medicines, including those obtained without a prescription, such as:

• 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.

Use of Carmustine Accordpharma 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 plan 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 fetus.

Therefore, this medicine should not normally be given to pregnant women. If used during pregnancy, the patient must be aware of the potential 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 treatment ends.

Male patients must use adequate contraception during treatment with carmustine and for at least 6 months after treatment ends to prevent their partners from becoming pregnant.

Male fertility may be affected by treatment with carmustine. Adequate counseling regarding fertility and family planning should be provided before starting carmustine treatment.

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 carmustine on the ability to drive and use machines is minor. You should consult your doctor before driving or operating any tools or machinery, as the alcohol content in this medicine may impair your ability to drive or operate machines.

Carmustine Accordpharma contains ethanol (alcohol)

This medicine contains 2.37 g of ethanol (alcohol) per 50 mg vial and 7.11 g of ethanol (alcohol) per 300 mg vial, equivalent to a maximum of 25.596 g per maximum dose (600 mg/m² in a 70 kg patient). The amount in the maximum dose of this medicine is equivalent to 640 ml of beer or 256 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 or breastfeeding, consult your doctor or pharmacist before taking this medicine.

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

Since this medicine is usually administered slowly over 1–2 hours, the effects of alcohol may be reduced.

3. How to use Carmustine Accordpharma

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

Recommended dose for adults

The dosage will depend on your medical condition, body size, and response to treatment. It is usually administered at least every 6 weeks. The recommended dose of carmustine as a single agent in patients who have not been previously treated is 150 to 200 mg/m² administered intravenously every 6 weeks. This may be given as a single dose or divided into daily infusions, such as 75 to 100 mg/m² on two consecutive days. The dose will also depend on whether carmustine is administered together with other anticancer medicines.

Doses will be adjusted according to your response to treatment.

The recommended dose of carmustine administered in combination with other chemotherapeutic agents prior to hematopoietic progenitor cell transplantation is 300 to 600 mg/m² administered 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, carmustine is administered intravenously via an infusion set (intravenous infusion) over a period of one to two hours, protected from light. The infusion duration should not be less than one hour to minimize 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 Accordpharma than you should

Since this medicine will be administered by a doctor or nurse, it is unlikely that you will receive an incorrect dose. However, 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 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 cell counts decrease
• Ataxia (lack of voluntary coordination of muscle movements)
• Dizziness
• Headaches
• Transient redness of the eyes, blurred vision due to retinal haemorrhage
• Hypotension (low blood pressure)
• Phlebitis (inflammation of the veins) associated with pain, swelling, redness, sensitivity
• Respiratory disorders (lung-related disorders) with breathing difficulties

This medicine may cause severe lung damage (possibly fatal). 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 leukaemias and bone marrow dysplasias (abnormal bone marrow development). Some 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, paleness, difficulty breathing, weakness, fatigue, or general decrease in energy.
• Anaemia (reduction in the number of red blood cells in the blood)
• Encephalopathy (brain disorder). This may include symptoms such as 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 (jaundice)
• Breathing problems caused by interstitial fibrosis (with lower doses)
• Kidney problems
• Gynaecomastia (enlargement of the breasts in males)

Frequency not known (cannot be estimated from available data)

• Muscle pain
• Seizures (fits), including epileptic status
• Tissue damage due to leakage at the injection site
• Any signs of infection
• Infertility
• Carmustine has been shown to have a negative effect on 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 effect, consult your doctor or nurse, even if it is a possible adverse effect 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 Accordpharma

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 “CAD” or “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 vials in the outer packaging to protect them from light.

After reconstitution (reconstituted stock solution)

The physicochemical stability in use of the reconstituted stock solution has been demonstrated for 24 hours at 2–8 °C.

After dilution (solution for infusion)

Chemical and physical in-use stability of the solution after dilution for infusion has been demonstrated when diluted in sodium chloride injection or 5% glucose injection to a final concentration of 0.2 mg/ml and stored in glass or polypropylene containers for 4 hours at 20 to 25 °C, protected from light. These solutions will also remain stable for 24 hours** when stored in a refrigerator (2 to 8 °C), followed by an additional 3 hours at 20 to 25 °C, protected from light.

From a microbiological point of view, unless the method of opening, reconstitution, and dilution excludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, the times and conditions of in-use storage are the responsibility of the user.

**The 24-hour in-use storage time of the final diluted solution is the total time carmustine is in solution, including the time during which it is reconstituted using ethanol and water for injections.

The solution must be protected from light until the end of administration.

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

6. Contents of the pack and other information

Composition of Carmustine Accordpharma

The active substance is carmustine.

Carmustine Accordpharma 50 mg

A 20 ml vial of powder for concentrate for solution for infusion contains 50 mg of carmustine.

A 5 ml vial of solvent contains 3 ml of anhydrous ethanol.

Carmustine Accordpharma 300 mg

A 100 ml vial of powder for concentrate for solution for infusion contains 300 mg of carmustine.

A 10 ml vial of solvent contains 9 ml of anhydrous ethanol.

After reconstitution with the solvent and dilution in water for injections, one ml of solution contains 3.3 mg of carmustine.

The other ingredients are:

• Powder: No excipients
• Solvent: Anhydrous ethanol

Appearance of Carmustine Accordpharma and contents of the pack

Powder and solvent for concentrate for solution for infusion.

The powder consists of a pale yellow lyophilized powder or flakes in an amber glass vial closed with a rubber stopper and sealed with an aluminium cap with a polypropylene flip-off seal.

The solvent is a clear, colourless liquid supplied in a clear glass vial closed with a rubber stopper and sealed with an aluminium cap with a polypropylene flip-off seal.

Pack sizes: The pack contains 1 vial with 50 mg of powder and 1 vial with 3 ml of solvent.

The pack contains 10 vials with 50 mg of powder and 10 vials with 3 ml of solvent.

The pack contains 1 vial with 300 mg of powder and 1 vial with 9 ml of solvent.

The pack contains 10 vials with 300 mg of powder and 10 vials with 9 ml of solvent.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Accord Healthcare S.L.U.

World Trade Center. Moll de Barcelona, s/n,

Edifici Est, 6th floor. 08039, Barcelona, Spain

Manufacturer:

Accord Healthcare Polska Sp. z o.o.

ul. Lutomierska 50,

95-200 Pabianice, Poland

Accord Healthcare single member S.A.

64th Km National Road Athens, Lamia,

Schimatari, 32009, Greece

This medicinal product has been authorised in the Member States of the European Economic Area under the following names

Member State	Medicinal Product Name
Finland	Carmustine Accordpharma 50 mg Powder and solvent for concentrate for infusion solution, solution Carmustine Accordpharma 300 mg Powder and solvent for concentrate for infusion solution, solution
Austria	Carmustine Accordpharma 50 mg Powder and solvent for concentrate for infusion solution Carmustine Accordpharma 300 mg Powder and solvent for concentrate for infusion solution
Germany	Carmustine Accordpharma 50 mg Powder and solvent for concentrate for infusion solution Carmustine Accordpharma 300 mg Powder and solvent for concentrate for infusion solution
Denmark	Carmustine Accordpharma 50 mg powder and solvent to concentrate for infusion solution, solution Carmustine Accordpharma 300 mg powder and solvent to concentrate for infusion solution, solution
Norway	Carmustine Accordpharma
Sweden	Carmustine Accordpharma 50 mg powder and liquid to concentrate for infusion solution, solution Carmustine Accordpharma 300 mg powder and liquid to concentrate for infusion solution, solution
France	Carmustine Accordpharma 50 mg Powder and solvent for solution to be diluted for infusion Carmustine Accordpharma 300 mg Powder and solvent for solution to be diluted for infusion
Spain	Carmustina Accordpharma 50 mg powder and solvent for concentrate for perfusion solution Carmustina Accordpharma 300 mg powder and solvent for concentrate for perfusion solution
Italy	Carmustina Accordpharma
Portugal	Carmustina Accordpharma
Ireland	Carmustine Accordpharma 50 mg powder and solvent for concentrate for solution for infusion Carmustine Accordpharma 300 mg powder and solvent for concentrate for solution for infusion
Poland	Carmustine Accordpharma

Date of the latest review of this leaflet: October 2025

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

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This information is intended for healthcare professionals only

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

Carmustine Accordpharma is a powder and solvent for concentrate for solution for infusion that contains no preservatives and is not designed for multiple use. Reconstitution and subsequent dilutions must be carried out under aseptic conditions.

If storage recommendations are followed, degradation of the unopened vial can be prevented until the expiry date indicated on the packaging.

The lyophilized product contains no preservatives and is intended for single use only. The lyophilized powder may appear as a fine powder; however, handling may cause it to appear as a heavier, clumped lyophilisate compared to a standard powder due to mechanical instability of the freeze-dried cake. The presence of an oily film may indicate melting of the drug. Such products must not be used due to the risk of exposure to temperatures exceeding 30°C. This medicinal product must not be used any further. When in doubt about whether the product has been adequately cooled, inspect each vial in the box immediately. For verification, hold the vial under bright light.

Reconstitution and dilution of the powder for concentrate for solution for infusion

Dissolve the carmustine (powder) with the required amount of sterile refrigerated ethanol solvent supplied in the primary container (brown glass vial). Carmustine must be completely dissolved in ethanol before adding sterile water for injection. Then, aseptically add the required amount of sterile water for injection to the alcoholic solution. The resulting stock solution must be thoroughly mixed.

Vial with powder	Vial with solvent (ethanol)	Volume of solvent required (ethanol)	Volume of water for injections required	Concentration of stock solution
50 mg	3 ml	1.5 ml	13.5 ml	3.3 mg/ml
300 mg	9 ml	9 ml	81 ml	3.3 mg/ml

Each ml of the reconstituted stock solution contains 3.3 mg of carmustine in 10% ethanol. Reconstitution as recommended results in a clear, colorless to yellowish stock solution, practically free from visible particles, which must be immediately diluted to the required volume with sodium chloride 9 mg/ml (0.9%) or 5% glucose injectable solution to obtain a final concentration of 0.2 mg/ml. The diluted solution (i.e., the ready-to-use solution) must be mixed for at least 10 seconds prior to administration. The ready-to-use solution should be administered over 1 to 2 hours.

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

pH: 3.2 to 7.0 when diluted in sodium chloride 9 mg/ml (0.9%) or 5% glucose injection solution.

Osmolality: 340 to 400 mOsmol/l (diluted in 50 mg/ml [5%] glucose or 9 mg/ml [0.9%] sodium chloride injection solution).

Method of administration

For intravenous use after reconstitution and dilution.

The reconstituted and diluted solution (i.e., the ready-to-use solution) must be administered intravenously via an intravenous infusion set over a period of one to two hours. The infusion must be administered using a polyethylene (PE) infusion set without PVC. During administration, a glass or polypropylene container must be used. Additionally, the ready-to-use solution must be protected from light (e.g., by wrapping aluminum foil around the container of the ready-to-use solution) and preferably maintained at temperatures below 20–25 °C, as carmustine degrades more rapidly at higher temperatures.

Shorter infusion periods of carmustine may cause intense pain and burning at the injection site. The infused area must be monitored during administration.

Guidelines for safe handling and disposal of antineoplastic agents must be followed.

Dosage and laboratory monitoring

Initial doses

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

When carmustine is used in combination with other myelosuppressive drugs 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 repeated cycle of carmustine must not be administered until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm³, leukocytes above 4,000/mm³), which usually occurs at six weeks. Blood counts should be monitored frequently, and cycles must not be repeated before six weeks due to delayed hematological toxicity.

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

Table 1

Nadir following previous dose	Percentage of previous dose to be given, %
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 following the initial dose does not fall within the same row for both leukocytes and platelets (e.g., leukocytes > 4000 and platelets < 25,000), the value associated with the lower percentage of the previous dose should be used (e.g., platelets < 25,000, then a maximum of 50% of the previous dose should be administered).

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

Preparative regimen prior to HSCT

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

Special populations

Pediatric population

Carmustine is contraindicated in children and adolescents under 18 years of age.

Elderly patients

In general, dose selection for elderly patients should be cautious, usually starting at the lower end of the dosing range, reflecting the higher frequency of impaired hepatic, renal, or cardiac function, as well as concomitant diseases or therapy with other medications. Since elderly patients are more likely to have reduced renal function, care should be taken in dose selection, and glomerular filtration rate should be monitored and dosage adjusted accordingly.

Renal impairment

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

Compatibility/Incompatibility with containers

The intravenous solution is unstable in polyvinyl chloride (PVC) containers. All plastic materials coming into contact with the carmustine infusion solution (e.g., infusion sets, etc.) must be PVC-free polyethylene plastic; otherwise, glassware should be used.