Patient leaflet - Carmustine 50 mg powder and solvent for concentrate for solution for infusion

1. What Carmustine is and what it is used for

Carmustine is a medicine which contains carmustine. Carmustine belongs to a group of anticancer medicines known as nitrosourea that act by slowing the growth of cancer cells.

Carmustine is used as palliative therapy (relieving and preventing the suffering of patients) as a single agent or in established combination therapy with other approved anticancer substances in certain types of cancers, like:

Brain tumours – glioblastoma, medulloblastoma, astrocytoma, and metastatic brain tumours
Multiple myeloma (malignant tumour developing from bone marrow)
Hodgkin’s disease (lymphoid tumour)
Non-Hodgkin’s lymphomas (lymphoid tumour)
Tumours of gastrointestinal tract or digestive system tract
Malignant melanoma (skin cancer).

Carmustine is also used as a conditioning therapy before transplantation of your own blood stem cells (autologous stem cell transplantation) in malignant haematological diseases of the lymphatic system (Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma).

2. What you need to know before Carmustine is given to you

Do not use Carmustine:

if you are allergic to carmustine or any of the other ingredients of this medicine (listed in section 6)
carmustine should not be used in patients who have reduced number of blood platelets (thrombocytes), white blood cells (leukocytes), or red blood cells (erythrocytes) either as a result of chemotherapy or from other causes
if you suffer from severe kidney function impairment
if the age of the patient is less than 18 years of age
if you are breast-feeding.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Carmustine.

Since the major side effect of this medicine is delayed bone marrow suppression, your doctor will monitor blood counts weekly for at least 6 weeks after a dose. At the recommended dosage, courses of carmustine would not be given more frequently than every 6 weeks. The dosage will be confirmed with the blood count.

Inform your doctor immediately if you experience any of the following symptoms:

Signs of infection (fever, persistent sore throat)
Enhanced tendency to bruising/bleeding
Unusual tiredness
Accelerated/throbbing heartbeat.
Before treatment, your liver and kidney function will be tested and observed regularly during treatment.
Gastrointestinal symptoms in the form of vomiting and nausea may occur during therapy.
Since the use of Carmustine can lead to lung damage, an X-ray of the chest region and lung function tests will be conducted before treatment is started (please also see the section “Possible side effects”).
High-dose treatment with Carmustine (up to 600 mg/m²) is only performed in combination with subsequent stem cell transplantation. Such a high dose can increase the frequency or severity of lung, kidney, liver, heart, and gastrointestinal toxicities as well as infections and disturbances in the electrolyte balance (low blood levels of potassium, magnesium, phosphate).
Stomach pain (neutropenic enterocolitis) may occur as a therapy-related adverse event during therapy with chemotherapeutic agents.
Patients who suffer from multiple conditions simultaneously and have poorer disease status are at higher risk for adverse events. This is especially important for elderly patients.
Your doctor will talk to you about the possibility of lung damage and allergic reactions and their symptoms. If such symptoms occur, you should contact your doctor immediately (see section 4).
Women of childbearing potential should use effective contraception while on treatment and for at least 6 months after treatment (please also see the section “Pregnancy, breast-feeding and fertility”). Men should take adequate precautions to ensure that your partner does not become pregnant during your treatment with carmustine and for at least 90 days after treatment.
Other medicines and Carmustine
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without prescription, such as:
- Phenytoin, used in epilepsy
- Cimetidine, used for stomach problems like indigestion
- Digoxin, used if you have abnormal heart rhythm
- Melphalan, an anticancer medicine
- Dexamethasone, used as an anti-inflammatory and immunosuppressive agent
- Methotrexate, cyclophosphamide, procarbazine, chlormethine (nitrogen mustard), fluorouracil, vinblastine, actinomycin (dactinomycin), bleomycin, doxorubicin (adriamycin) used for treatment of various types of cancers.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy and fertility

Carmustine should not be used during pregnancy because it may harm your unborn baby. Therefore, this medicine should not normally be administered to pregnant women. If used during pregnancy, the patient must be aware of the potential risk to the unborn baby. Women of childbearing potential are advised to use effective contraception to avoid becoming pregnant whilst being treated with this medicine and for at least 6 months after treatment.

Male patients should use adequate contraceptive measures during treatment with Carmustine and for at least 90 days after treatment to prevent their partners becoming pregnant. The fertility of male patients may be affected by treatment with Carmustine. You should seek adequate counselling regarding fertility/family planning before initiating treatment with Carmustine.

Breast-feeding

You must not breast-feed while taking this medicine and up to 7 days after completion of treatment. A risk to the newborn/infant cannot be excluded.

Driving and using machines

The effect of this medicine on your ability to drive and use machines is not known. You must check with your doctor before driving or operating any tools or machines because the amount of alcohol in this medicine may impair your ability to drive or use machines.

Carmustine contains ethanol (alcohol)

This medicine contains 2.4 g of alcohol (ethanol) per vial for the 50 mg strength and 7.1 g of alcohol (ethanol) per vial for the 300 mg strength, which is equivalent to 25.92 g per maximal dose (10 vol %). The amount in maximal dose (600 mg/m²in 70 kg patient) of this medicine is equivalent to 648 ml beer or 259 ml wine.

The amount of alcohol in this medicine can affect your ability to drive or use machines. This is because it may affect your judgement and how fast you react.

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 or breast-feeding, talk to your doctor or pharmacist before taking this medicine.

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

3. How to use Carmustine

Carmustine will always be given to you by a healthcare professional with experience in the use of anticancer medicines.

Recommended dose for adults

Dosage is based on your medical condition, body size and response to treatment. It is usually given at least every 6 weeks. The recommended dose of Carmustine as a single agent in previously untreated patients is 150 to 200 mg/m²intravenously every 6 weeks. This may be given as a single dose or divided into daily infusions such as 75 to 100 mg/m²on two successive days. Dosage will also depend on whether Carmustine is given with other anti-cancer medicines.

Doses will be adjusted according to how you respond to the treatment.

The recommended dose of Carmustine given in combination with other anticancer substances before autologous stem cell transplantation is 300 – 600 mg/m²intravenously.

Your blood count will be monitored frequently to avoid toxicity in your bone marrow and the dose adjusted if necessary.

Route of administration

Following reconstitution and dilution Carmustine is given into a vein by a drip (intravenously) over a one to two hour period protected from light. The duration of infusion should not be less than one hour to avoid burning and pain at the injected area. The injected area will be monitored during the administration.

The duration of the treatment is determined by the doctor and may vary for each patient.

Use in children and adolescents (age <18 years)

Carmustine cannot be used in children and adolescents due to high risk of lung toxicity.

Use in elderly

Carmustine can be used with caution in elderly patients. The kidney function will be carefully monitored.

If you use more Carmustine than you should

As a doctor or nurse will be giving you this medicine, it is unlikely that you will receive an incorrect dose. Tell your doctor or nurse if you have any concern about the amount of medicine that you received.

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 notice any of the following:

Any sudden wheeziness, difficulty in breathing, swelling of the eyelids, face or lips, rash or itching (especially affecting your whole body), and feeling 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):

Delayed myelosuppression (decrease in blood cells in bone marrow) which can increase the chance of infections if white blood cells are decreased
Ataxia (lack of voluntary coordination of muscle movements)
Dizziness
Headache

70 mm

10 6760 1 6026539 Carmustine 50 mg, 300 mg

10 6760 1 6026539

Carmustine

50 mg, 300 mg

(6026539) Date: 07/10/2023, (R) 10_01_2024, 16_01_2024

When Carmustine is used in combination with other myelosuppressive medicinal products or in patients in whom bone marrow reserve is depleted, the doses should be adjusted according to the haematologic profile of the patient as shown below .

Monitoring and subsequent doses

A repeat course of Carmustine should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/ mm³, leukocytes above 4,000/ mm³), and this is usually in six weeks. Blood counts should be monitored frequently and repeat courses should not be given before six weeks because of delayed haematologic toxicity.

Doses subsequent to the initial dose should be adjusted according to the haematologic response of the patient to the preceding dose, in both monotherapy as well as in combination therapy with other myelosuppressive medicinal products. The following schedule is suggested as a guide to dosage adjustment:

Table 1

In cases where the nadir after initial dose does not fall in the same row for leucocytes and platelets (e.g. leucocytes >4,000 and platelets <25,000) the value given the lowest percentage of prior dose should be used (e.g. platelets <25,000 then a maximum of 50% of prior dose should be given).

Conditioning treatment prior to SCT

Carmustine is given in combination with other chemotherapeutic agents in patients with malignant haematological diseases before SCT at a dose of 300 - 600 mg/m²intravenously.

Special populations

Patients with impaired renal function

In patients with impaired renal function the dose of Carmustine should be reduced depending on the glomerular filtration rate.

Elderly

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dose range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or therapy with other medicinal products.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored and the dose reduced according to this.

Paediatric population

Carmustine is contraindicated in children and adolescents aged <18 years due to the high risk of pulmonary toxicity.

Compatibility/Incompatibility with containers

The intravenous solution is unstable in polyvinyl chloride containers. All plastic coming into contact with the carmustine solution for infusion (e.g. infusion set etc.) should be PVC free polyethylene plastic, otherwise glass ware should be used.

Transient redness in the eye, blurred vision, retinal bleeding, inflammation of the iris and optic nerve
Hypotension (fall in blood pressure) with high-dose therapy
Phlebitis (inflammation of the veins) associated with pain, swelling, redness, tenderness
Respiratory disorders (lung related disorders) with breathing problems. This medicine may cause severe (possibly fatal) lung damage. Lung damage may occur years after treatment. Tell your doctor immediately if you experience any of the following symptoms: shortness of breath, persistent cough, chest pain, persistent weakness/tiredness
Severe nausea and vomiting; beginning within 2-4 hours of administration and lasting for 4-6 hours
When used on the skin, inflammation of the skin (dermatitis)
Accidental contact with skin 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 development of the bone marrow) following long term use. Symptoms may include bleeding gums, bone pain, fever, frequent infections, frequent or severe nosebleeds, lumps caused by swollen lymph nodes in and around the neck, underarm, abdomen or groin, pale skin, shortness of breath, weakness, fatigue or a general lack of energy
Anaemia (decrease in the amount of red blood cells in the blood)
Encephalopathy (disorder of brain) in high-dose therapy. Symptoms may include muscle weakness in one area, poor decision-making or concentration, involuntary twitching, trembling, difficulty speaking or swallowing, seizures
Loss of appetite (anorexia)
Constipation
Diarrhoea
Inflammation of the mouth and lips
Reversible liver toxicity in high-dose therapy, delayed up to 60 days after administration. This can result in increased liver enzymes and bilirubin (detected by blood tests)
Alopecia (loss of hair)
Flushing of the skin
Reactions on the injection site.

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

Veno-occlusive disease (progressive blockage of the veins) in high-dose therapy, where very small (microscopic) veins in the liver become blocked. Symptoms may include: fluid accumulation in the abdomen, enlargement of spleen, severe bleeding of the oesophagus, yellowing of skin and whites of the eyes
Breathing problems due to a type of lung disease in which lung tissue is scarred (interstitial fibrosis) (with lower doses). Symptoms may include dry cough, shortness of breath, fatigue, weight loss
Kidney problems
Gynecomastia (breast growth in males)
Inflammation of the optic nerve and adjacent retina in the eye
Bleeding in the gastrointestinal tract.

Very rare (may affect up to 1 in 10,000 people):

Inflammatory process that causes a blood clot to form and block one or more veins, usually in the legs. The affected vein might be near the surface of your skin or deep within a muscle (thrombophlebitis).

Not known (frequency cannot be estimated from the available data):

Allergic reactions
Muscular pain
Secondary tumours (cancers caused by radiation or chemotherapy)
Seizures (fits) including status epilepticus
Tissue damage due to leakage in injection area
Infertility
Impairment of embryo/foetus development in pregnant women
Any signs of infection
Fast heartbeat, chest pain
Disturbances in electrolyte balance (low blood levels of potassium, magnesium, phosphate)
Abdominal pain (neutropenic enterocolitis)
Decrease in renal volume, progressive accumulation of certain metabolic products in the blood (azotaemia) and kidney failure were observed after high cumulative doses and after long-term treatment with carmustine and other nitrosoureas. Renal damage was also observed after lower total doses.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Carmustine

This medicine will be stored by your doctor or health care 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 refers to the last day of that month.

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

Keep the vials in the outer carton in order to protect from light.

After reconstitution (reconstituted stock solution)

Chemical and physical in-use stability of reconstituted stock solution has been demonstrated for 24 hours at 2 to 8°C.

After dilution (solution after dilution for infusion)

Chemical and physical in-use stability of solution after dilution for infusion in sodium chloride solution for injection or 5% glucose solution for injection at final concentration of 0.2 mg/ml and stored in a glass or polypropylene container has been demonstrated for 6 hours at 20 to 25°C, protected from light. These solutions will also remain stable for 24 hours in cold storage (2 to 8 °C) and a further 4 hours at 20 to 25 °C, protected from light.

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

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Carmustine contains

The active substance is carmustine.

Carmustine 50 mg

One 20 ml vial of powder for concentrate for solution for infusion contains 50 mg carmustine. One 5 ml vial of solvent contains 3 ml of ethanol anhydrous.

Once the solution is reconstituted with the solvent provided and further diluted with sterile water, one ml of solution will contain 3.3 mg of carmustine.

Carmustine 300 mg

One 100 ml vial of powder for concentrate for solution for infusion contains 300 mg carmustine. One 10 ml vial of solvent contains 9 ml of ethanol anhydrous.

Once the solution is reconstituted with the solvent provided and further diluted with sterile water, one ml of solution will contain 3.3 mg of carmustine.

The other ingredients are:

Powder: No excipients.
Solvent: Ethanol anhydrous.

What Carmustine looks like and contents of the pack

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

The powder is pale yellow dry flakes or dry congealed mass is in a type I amber glass vial sealed with rubber stopper and aluminium seal having polypropylene cap.

The solvent is a clear colourless liquid in a type I clear glass vial sealed with rubber stopper and aluminium seal having polypropylene cap.

Pack sizes: Pack contains 1 vial of 50 mg powder and 1 vial of 3 ml solvent Pack contains 1 vial of 300 mg powder and 1 vial of 9 ml solvent

Marketing Authorisation Holder and Manufacturer

Accord Healthcare Limited

Sage House, 319 Pinner Road

North Harrow, Middlesex

HA14HF

United Kingdom

This leaflet was last revised in January 2024

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