Consumer medicine information

Carmustine Juno

Carmustine

BRAND INFORMATION

Brand name

Carmustine Juno

Active ingredient

Carmustine

Schedule

What is in this leaflet

This leaflet answers some common questions about CARMUSTINE JUNO®. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CARMUSTINE JUNO against the benefits that are expected. This leaflet does not contain everything about CARMUSTINE JUNO. Your doctor has been provided with full information and can answer any questions you may have. Follow your doctor's advice even if it differs from what is in this leaflet.

Please read this leaflet carefully and keep it in a safe place so you may refer to it later.

What CARMUSTINE JUNO is used for

CARMUSTINE JUNO is used to treat malignant glioma, a type of brain cancer, and multiple myeloma, a cancer of the blood. It may also be used to treat other types of cancers called Hodgkin's Disease and Non-Hodgkin's lymphomas.

CARMUSTINE JUNO belongs to a group of medicines called cytotoxic medicines. You may also hear of these being called chemotherapy medicines. CARMUSTINE JUNO may be used in combination with other medicines to treat your cancer.

Your doctor may have prescribed CARMUSTINE JUNO for another use. Ask your doctor if you have any questions about why CARMUSTINE JUNO was prescribed for you.

This medicine is available only with a doctor's prescription.

How CARMUSTINE JUNO works

CARMUSTINE JUNO works by killing cancer cells.

The use of CARMUSTINE JUNO to treat your condition can lead to side-effects, which are discussed below.

Before you are given CARMUSTINE JUNO

When you must not be given it

You must not have CARMUSTINE JUNO if you have a history ofsevere allergic reactions to CARMUSTINE JUNO or to any of the ingredients listed at the end of this leaflet.

Do not have CARMUSTINE JUNO if you have, or have had, any of the following medical conditions, unless you have discussed it with your doctor:

kidney problems
lung disease
blood disorder with a reduced number of white blood cells
blood disorder with a low blood platelet count
blood disorder with a decreased number of red blood cells
lowered immunity due to treatment with medicines such as corticosteroids, cyclosporin or other medicines used to treat cancer

Tell your doctor if you have an infection or high temperature. Your doctor may decide to delay your treatment until the infection has gone. A mild illness, such as a cold, is not usually a reason to delay treatment.

Females: tell your doctor if you are pregnant or intend to become pregnant. Like most cytotoxic medicines, CARMUSTINE JUNO is not recommended for use during pregnancy. If there is any need to consider CARMUSTINE JUNO during your pregnancy, your doctor will discuss with you the benefits and risks of using it. CARMUSTINE JUNO may affect your developing baby if you take it during pregnancy.

Males: tell your doctor if your partner intends to become pregnant while you are using CARMUSTINE JUNO or shortly after you have stopped using CARMUSTINE JUNO.

You should use some kind of birth control while you are using CARMUSTINE JUNO and for at least 12 weeks after you stop using it. CARMUSTINE JUNO may cause birth defects if either the male or female is using it at the time of conception.

Do not breastfeed while using CARMUSTINE JUNO. It is not known whether CARMUSTINE JUNO passes into breast milk. Therefore there is a possibility that the breast-fed baby may be affected.

If you are not sure whether you should start having CARMUSTINE JUNO, talk to your doctor.

Before you are given it

Tell your doctor if you have allergies to:

any other medicines
any other substances, such as foods, preservatives or dyes

Tell your doctor if you have or have had any medical conditions, especially the following:

liver problems
kidney problems
heart problems, including a heart attack
lung problems, including asthma
blood disorder with a reduced number of red or white blood cells
If you are pregnant or intend to become pregnant.
If you are breast-feeding or intend to breast-feed.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket or health food shop. Some medicines and CARMUSTINE JUNO may interfere with each other. These medicines may be affected by CARMUSTINE JUNO, or may affect how well it works. You may need different amounts of your medicine, or you may need to have different medicines. Your doctor will advise you.

CARMUSTINE JUNO when used in combination with other medicines or radiation therapy may further depress your immune system.

Your doctor may have more information on medicines to be careful with or avoid while having CARMUSTINE JUNO.

If you have not told your doctor about any of the above, tell them before you start having CARMUSTINE JUNO.

While you are receiving CARMUSTINE JUNO

Things you must do:

Tell your doctor immediately if you become pregnant while taking CARMUSTINE JUNO.
Tell all of the doctors, dentists and pharmacists who are treating you that you are taking CARMUSTINE JUNO.
If you are about to be started on any new medicine, tell your doctor and pharmacist that you are taking CARMUSTINE JUNO.
Be sure to keep all your doctor's appointments so your progress can be checked. Your doctor may want to check your blood pressure and do some blood and other tests from time to time to check on your progress and detect any unwanted side effects.
Keep follow up appointments with your doctor. It is important to have your follow-up doses of CARMUSTINE JUNO at the appropriate times to get the best effects from your treatments. If you forget a hospital appointment immediately contact your doctor.

CARMUSTINE JUNO can lower the number of white blood cells and platelets in your blood. This means that you have an increased chance of getting an infection or bleeding. The following precautions should be taken to reduce your risk of infection or bleeding:

Avoid people who have infections. Check with your doctor immediately if you think you may be getting an infection, or if you get a fever, chills, cough, hoarse throat, lower back or side pain or find it painful or difficult to urinate.
Be careful when using a toothbrush, toothpick or dental floss. Your doctor, dentist, nurse or pharmacist may recommend other ways to clean your teeth and gums. Check with your doctor before having any dental work.
Be careful not to cut yourself when you are using sharp objects such as a razor or nail cutters.
Avoid contact sports or other situations where you may bruise or get injured.

Things you must not do:

Do not drink alcohol while taking CARMUSTINE JUNO. You may feel flushed or get headaches.

Things to be careful of:

As with other anticancer medicines, CARMUSTINE JUNO may cause nausea, dizziness or tiredness in some people. Make sure you know how you react to CARMUSTINE JUNO before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or tired. If this occurs do not drive. If you drink alcohol, dizziness or tiredness may be worse.

How CARMUSTINE JUNO is given

Your doctor will decide what dose of CARMUSTINE JUNO you will receive based in the characteristics of your cancer. The dose also depends on your condition and other factors, such as your weight, kidney function and other chemotherapy medicines you are being given. CARMUSTINE JUNO may be given alone or in combination with other drugs.

CARMUSTINE JUNO is administered as a slow infusion into your vein, over 1 to 2 hours. The infusion will be prepared and given in hospital by your doctor or nurse.

How long is CARMUSTINE JUNO given

CARMUSTINE JUNO is usually given every six weeks. This is called one cycle of chemotherapy. Your doctor will decide how many of these cycles you will need.

Several courses of CARMUSTINE JUNO therapy may be needed depending on your response to treatment.

Additional treatment may not be repeated until your blood cell numbers return to acceptable levels and any uncontrolled effects have been controlled.

Ask your doctor if you want to know more about the dose of CARMUSTINE JUNO you receive.

Overdose

As CARMUSTINE JUNO is given to you under the supervision of your doctor, it is very unlikely that you will receive too much. However, if you experience any side effects after being given CARMUSTINE JUNO, tell your doctor or nurse immediately or go to Accident and Emergency at your nearest hospital. You may need urgent medical attention.

Symptoms of a CARMUSTINE JUNO overdose include the side effects listed below in the "Side Effects" section, but are usually of a more severe nature.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are receiving CARMUSTINE JUNO.

Like all medicines, it is possible that CARMUSTINE JUNO may have unwanted side effects in some people. During treatment with CARMUSTINE JUNO you will require close medical supervision.

The more common side effects of CARMUSTINE JUNO are:

Suppression of your immune system; reduced white blood cells, reduced platelets, reduced red blood cells
Nausea, vomiting
Lung toxicity
Respiratory disorders (lung related disorders) with breathing problems

Tell your doctor or nurse immediately or if you are not currently in hospital, go to accident and emergency at your nearest hospital if you notice any of the following:

Symptoms of an allergic reaction, such as:
- shortness of breath, wheezing, difficulty breathing or a tight feeling in your chest
- swelling of the face, lips, tongue or other parts of the body
- rash, itching, hives or flushed, red skin
- dizziness or light headedness
Frequent infections, fever, severe chills, sore throat or mouth ulcers
Bleeding or bruising more easily than normal
Passing little or no urine, drowsiness, nausea, vomiting and breathlessness
Weakness, tiredness, loss of appetite, weight loss and stomach pain
Changes to vision or loss of sight
Shortness of breath, particularly with exertion, chronic dry, hacking coughing
Chest discomfort, irregular heartbeat
Loss of appetite and rapid weight loss
Pain, swelling or burning at the injection site

These are serious side effects. You may need urgent medical attention or hospitalisation.

Other side effects not listed above may also occur in some patients. Tell your doctor if you notice anything else that is making you feel unwell.

Product Description

CARMUSTINE JUNO is a pale yellow powder. Each CARMUSTINE JUNO 100mg amber vial comes with a clear vial containing the ethanol required for the preparation of the infusion.

Active ingredient: carmustine

Other ingredient: ethanol (required for preparation of the infusion)

Storage

CARMUSTINE JUNO will be stored in the pharmacy or on the hospital ward. The unopened vials of the dry powder will be stored under refrigeration.

Registration Numbers

CARMUSTINE JUNO - Each carton contains a vial containing 100 mg carmustine and a clear glass vial containing 3 mL ethanol - AUST R 319034.

Where to get further information

Your doctor is the best person to answer any further questions you may have about CARMUSTINE JUNO. Anything your doctor tells you about CARMUSTINE JUNO should be followed even if it is different from what is in this leaflet.

This leaflet was prepared in November 2020.

Published by MIMS May 2021

BRAND INFORMATION

Brand name

Carmustine Juno

Active ingredient

Carmustine

Schedule

1 Name of Medicine

Carmustine.

2 Qualitative and Quantitative Composition

Each carton includes a vial containing 100 mg carmustine and a vial containing 3 mL ethanol absolute sterile diluent.

3 Pharmaceutical Form

Carmustine 100 mg/vial is lyophilized pale yellow flakes or congealed mass or powder in an amber glass vial. Sterile ethanol absolute is a clear, colourless liquid in a clear glass vial.

4 Clinical Particulars

4.1 Therapeutic Indications

Carmustine Juno is indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in the following:
1. Malignant glioma.
2. Multiple myeloma - in combination with prednisone.
3. Hodgkin's disease - as secondary therapy in combination with other approved drugs in patients who relapse while being treated with primary therapy, or who fail to respond to primary therapy.
4. Non-Hodgkin's lymphomas - as secondary therapy in combination with other approved drugs for patients who relapse while being treated with primary therapy or who fail to respond to primary therapy.

4.2 Dose and Method of Administration

Carmustine Juno is administered by slow intravenous infusion. Carmustine Juno should not be given by rapid intravenous injection.
The recommended dose of Carmustine Juno as a single agent in previously untreated patients is 200 mg/m² intravenously every 6 weeks. This may be given as a single dose or divided into daily injections such as 100 mg/m² on successive days. When Carmustine Juno is used in combination with other myelosuppressive drugs or in patients in whom bone marrow reserve is depleted, the doses should be adjusted accordingly.
A repeat course of Carmustine Juno should not be given until circulating blood elements have returned to acceptable levels (platelets above 100,000/mm³; leucocytes above 4,000/mm³); this usually occurs within 6 weeks. Blood counts should be monitored frequently and repeat courses should not be given before 6 weeks because of delayed toxicity.
In view of the cumulative dose-related toxicity which occurs with Carmustine Juno the total dose administered should not exceed 1500 mg/m², unless the expected benefits outweigh the high risk of toxicity, especially pulmonary (see Section 4.8 Adverse Effects (Undesirable Effects)).
Doses subsequent to the initial dose should be adjusted according to the haematologic response of the patient to the preceding dose. The schedule in Table 1 is suggested as a guide to dosage adjustment:

Preparation of intravenous solutions.

To facilitate reconstitution, allow Carmustine Juno and the supplied sterile diluent (absolute ethanol) to come to controlled room temperature (15° to 30°C) before mixing. Dissolve Carmustine Juno completely with 3 mL of the supplied sterile diluent and then aseptically add 27 mL of sterile water for injection to the alcohol solution. Each mL of the resulting solution will contain 3.3 mg of carmustine in 10 percent ethanol having pH of 5.6 to 6.0 (solution in the ethanol must be complete before sterile water for injection is added). Accidental contact of reconstituted Carmustine Juno with the skin has caused transient hyperpigmentation of the affected areas. If Carmustine Juno lyophilized material or solution contact the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water.
Reconstitution as recommended results in a clear, colourless to light yellow solution which may be further diluted with either 0.9% sodium chloride solution for injection or 5% glucose solution for injection. The reconstituted solution should be used intravenously only and should be administered by IV drip over a 1 to 2 hour period. Injection of Carmustine Juno over shorter periods of time may produce intense pain and burning at the site of injection.
Use only glass containers for preparation and administration.

Important note.

Product is for single use in one patient only. Discard any residue.

4.3 Contraindications

Should not be given to individuals who have demonstrated a previous hypersensitivity to it.
Should not be given to individuals with decreased circulating platelets, leucocytes, or erythrocytes either from previous chemotherapy or other causes.

4.4 Special Warnings and Precautions for Use

Bone marrow suppression, notably thrombocytopenia and leucopenia, which may contribute to bleeding and overwhelming infections in an already compromised patient, is the most common and severe of the toxic effects of carmustine.
Carmustine has been administered directly into the carotid artery; this procedure is investigational and has been associated with ocular toxicity.
Pulmonary toxicity from carmustine appears to be dose related. Patients receiving greater than 1400 mg/m² cumulative dose are at significantly higher risk than those receiving less.
Delayed pulmonary toxicity can occur years after treatment, and can result in death, particularly in patients treated in childhood (see Section 4.8 Adverse Effects (Undesirable Effects)).

Identified precautions.

Carmustine should be administered preferably by individuals experienced in antineoplastic therapy.
It is recommended that liver and renal function tests be monitored.
Patients with pre-existing lung disease are at greater risk of developing carmustine-associated pulmonary toxicity. Thoracic irradiation and other drugs affecting the pulmonary function have also been implicated as predisposing to development of pulmonary toxicity during treatment with carmustine.
Baseline pulmonary function studies should be conducted along with frequent pulmonary function tests during treatment. Patients with a baseline below 70 percent of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DL_CO) are particularly at risk.
Since delayed bone marrow toxicity is the major toxicity, complete blood counts should be monitored frequently for at least 6 weeks after a dose. Repeat doses of carmustine should not be given more frequently than every 6 weeks.
The bone marrow toxicity of carmustine is cumulative, and therefore dosage adjustment must be considered on the basis of nadir blood counts from prior dose (see Section 4.2 Dose and Method of Administration, Table 1).
Injection site reactions may occur during the administration of carmustine (see Section 4.8 Adverse Effects (Undesirable Effects)). Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during drug administration. A specific treatment for extravasation reactions is unknown at this time.

Use in the elderly.

No data available.

Paediatric use.

Safety and effectiveness in children have not been established. Same monitoring and dose modification principles apply as for adults (see Section 4.8 Adverse Effects (Undesirable Effects)).

Effects on laboratory tests.

None known.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Carmustine may need to be used with caution in combination chemotherapy (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Carmustine affects fertility in male rats at doses somewhat higher than the human dose.
(Category D)
Safe use in pregnancy has not been established. Therefore, the benefit to the mother versus the risk of toxicity to the mother and the fetus must be carefully weighed.
Carmustine is embryotoxic and teratogenic in rats and embryotoxic in rabbits at dose levels equivalent to human dose.

Instructions to be given to patient.

Patients should be advised to use adequate contraceptive measures during treatment with carmustine.
It is not known whether carmustine is excreted in human milk nor whether it has a harmful effect on the newborn. Therefore, administration is not recommended for nursing mothers unless alternative methods of feeding the infant are established.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions reported have been grouped by frequency according to the following criteria.
Very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10,000 and < 1/1000; very rare < 1/10,000.

Haematological.

Very common: Myelosuppression (delayed; usually occurs 4 to 6 weeks after drug administration and is dose related). Platelet nadirs occur at 4 to 5 weeks; leucocyte nadirs occur at 5 to 6 weeks post-therapy. Thrombocytopenia is generally more severe than leucopenia (both may be dose limiting); anaemia.
Common: Cumulative myelosuppression after repeated doses (manifested by more depressed indices or longer duration of suppression).
Rare: Acute leukaemia and bone marrow dysplasias following long-term therapy; thrombosis.

Gastrointestinal.

Very common: Nausea: vomiting (occurs within 2 hours, usually lasts 4-6 hours and is dose dependant).

Hepatic.

Uncommon: Elevated transaminases, alkaline phosphatase and bilirubin.
Rare: Fatal hepatic toxicity (cumulative doses over 1200-1500 mg/m²) has occurred.

Renal.

Uncommon: Decrease in kidney size; progressive azotaemia; renal failure.

Pulmonary.

Common: Pulmonary infiltrates and/or fibrosis (high cumulative dose greater than 1400 mg/m²). This toxicity has occurred from 9 days to 43 months after treatment.
In a long-term study of 17 patients who survived childhood brain tumors, very delayed onset pulmonary toxicity occurring up to 15 years after treatment with carmustine has been reported. These children ranged between 2 and 16 years of age when treated with carmustine at doses of 800 mg/m² or above. All received cranial irradiation and most received spinal radiotherapy. Chest X-rays and CT scans have demonstrated upper zone fibrotic changes primarily. All children exhibited reduced pulmonary function and the toxicity was shown to be progressive, resulting in death in approximately 50% of cases. Severity was related to age at treatment with five children treated at age less than 5 years having died of pulmonary fibrosis.
Uncommon: Pulmonary fibrosis (low cumulative dose).
Pulmonary toxicity is also manifested as pneumonitis and interstitial lung disease in postmarketing experience.

Ophthalmic.

Rare: Neuroretinitis; suffusion of conjunctiva (from rapid IV infusion).

Skin and appendages.

Uncommon: Facial flushing; burning at site of injection; hyperpigmentation from accidental skin contact, extravasation*.

Cardiovascular.

Uncommon: Hypotension; tachycardia; chest pain.

Hypersensitivity.

Uncommon: Allergic reactions.

Neurological.

Uncommon: Headache.
* Complications reported for extravasation included local soft tissue toxicity, swelling, pain, erythema, burning sensation, and skin necrosis.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

No information is available relating to carmustine poisoning in humans. Treatment will be mainly supportive. Haematological and gastrointestinal toxic effects are expected to be the principal manifestations of carmustine overdosage.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Carmustine alkylates DNA and RNA and has been shown to inhibit several enzymes by carbamoylation of amino acids in proteins. Carmustine is not cross resistant with other alkylators.
It is thought that the antineoplastic and toxic activities of carmustine may be due to metabolites.

Clinical trials.

No information available.

5.2 Pharmacokinetic Properties

Distribution.

Intravenously administered carmustine is rapidly degraded, with no intact drug detectable after 15 minutes. However, in studies with ¹⁴C labelled drug prolonged levels of the isotope were observed in the plasma and tissue, probably representing radioactive fragments of the parent compound.
Because of the high lipid solubility and the relative lack of ionization at a physiological pH, carmustine crosses the blood brain barrier quite effectively. Levels of radioactivity in the CSF are 50% or greater than those measured in plasma.

Excretion.

Approximately 60 to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory carbon dioxide. The fate of the remainder is undetermined.

5.3 Preclinical Safety Data

Genotoxicity.

No information available.

Carcinogenicity.

Carmustine is carcinogenic in rats and mice, producing a marked increase in tumour incidence in doses approximately those employed clinically.
Nitrosourea therapy does have carcinogenic potential. The occurrence of acute leukaemia and bone marrow dysplasias have been reported in patients following nitrosourea therapy.

6 Pharmaceutical Particulars

6.1 List of Excipients

Not applicable.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Product should be shipped and stored at 2°C to 8°C. (Refrigerate. Do not freeze).

Important note.

Carmustine has a low melting point (approximately 30.5°C-32.0°C). Exposure of the drug to this temperature or above will cause the drug to liquefy and appear as an oil film in the bottom of the vials. This is a sign of decomposition and vials should be discarded.
The stability of reconstituted solutions has not been demonstrated and their use should be commenced immediately after preparation.

6.5 Nature and Contents of Container

Each package includes a vial containing 100 mg carmustine and a vial containing 3 mL sterile diluent.
Carmustine 100 mg/vial powder for injection is presented in a 30 mL amber colour glass vial stoppered with grey rubber stoppers and sealed with a green flip-off aluminium seal.
Sterile ethanol absolute diluent for injection is supplied in a 3 mL clear glass vial stoppered with grey rubber stoppers and sealed with a green flip-off aluminium seal.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Carmustine is one of the nitrosoureas. The chemical name is 1,3-bis(2-chloroethyl)-1-nitrosourea.
Carmustine is a pale yellow powder with a molecular weight of 214.06. It is highly soluble in alcohol and poorly soluble in water. It is also highly soluble in lipids. One gram of carmustine is soluble in approximately 250 mL of 0.9% saline solution or 80 mL of propylene glycol.

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