Consumer medicine information

What is in this leaflet

This leaflet answers some common questions about CYCLONEX®. It does not contain all the available information.

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 CYCLONEX against the benefits this medicine is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What CYCLONEX is used for

CYCLONEX is used to treat certain types of cancer such as:

• malignant lymphoma, a cancer of the lymph glands
• multiple myeloma, type of blood cancer
• leukaemia, type of blood cancer
• mycosis fungoides, a cancer of the lymph glands which affects the skin
• neuroblastoma, a cancer of nerves and the adrenal glands
• ovarian cancer
• a type of cancer called retinoblastoma
• breast cancer and
• some types of lung cancers

CYCLOBLASTIN is also used to:

• treat certain types of diseases of the immune system when other treatments have not worked
• prevent the body from rejecting organ transplants.

How CYCLONEX works

CYCLONEX belongs to a group of medicines called antineoplastic medicines. You may also hear of these being called chemotherapy medicines.

In the treatment of cancer, CYCLONEX works by stopping cancer cells from growing and multiplying.

Your doctor may have prescribed CYCLONEX for another reason. Ask your doctor if you have any questions about why CYCLONEX has been prescribed for you.

CYCLONEX is not addictive.

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

Before you take CYCLONEX

When you must not take CYCLONEX

Do not use CYCLONEX if you have an allergy to:

• cyclophosphamide, the active ingredient in CYCLONEX
• any of the other ingredients in CYCLONEX listed at the end of this leaflet.

Symptoms of an allergic reaction to CYCLONEX may include:

• shortness of breath
• wheezing or difficulty breathing
• swelling of the face, lips, tongue or other parts of the body
• rash, itching or hives on the skin
• light-headedness
• back pain.

Do not use CYCLONEX if you have an infection.

Do not use CYCLONEX if you have any of the following medical conditions:

• cystitis (pain in the bladder or back, blood in urine)
• urinary infection
• difficulty passing urine
• drug or radiation induced inflammation of the urinary tract.

Do not use CYCLONEX if you have had major surgery in the last 4 to 8 days.

Do not use CYCLONEX in the first 3 months of pregnancy. If you are more than 3 months pregnant, discuss using CYCLOBLASTIN with your doctor before starting the treatment.

Do not use CYCLONEX after the expiry date (EXP) printed on the pack.

Do not use CYCLONEX if the packaging is torn or shows signs of tampering.

If you are not sure whether you should use CYCLONEX, talk to your doctor.

Before you start to take CYCLONEX

Tell your doctor if you have an allergy to:

• cyclophosphamide, the active ingredient in CYCLONEX
• any of the other ingredients in CYCLONEX listed at the end of this leaflet
• 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)
• acute porphyria (a blood disorder)
• diabetes
• leukopenia (lack of white blood cells resulting in frequent infections, fever, severe chills, sore throat or mouth ulcers)
• thrombocytopenia (low blood platelet count resulting in bleeding or bruising more easily than normal)
• problems with your adrenal glands.

Tell your doctor if you are taking insulin or other drugs for diabetes, barbiturates or you are having or have recently had corticosteroid therapy.

Tell your doctor if you have had previous chemotherapy, x-ray or radiotherapy.

Tell your doctor if you are or have been taking any other medicine for cancer.

Tell your doctor if you are pregnant or intend to become pregnant.CYCLONEX should not be used during pregnancy, particularly in the first three months of pregnancy.

If there is any need to consider giving you CYCLONEX during your pregnancy, your doctor or pharmacist will discuss with you the benefits and risks of using it.

Use a proven method of birth control, such as the contraceptive pill or a condom, while taking the medicine and for at least 12 weeks after stopping treatment.

The medicine may cause birth defects if either you or your partner is taking it.

If you become pregnant while using this medicine, tell your doctor immediately.

Following treatment with CYCLONEX you or your partner may not be able to become pregnant. Ask your doctor to discuss this with you.

Tell your doctor if you are breastfeeding or plan to breastfeed.

If you have not told your doctor about any of the above, tell them before you start using CYCLONEX.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including medicines that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines, procedures and CYCLONEX may interfere with each other. These include:

• radiation therapy or any other treatment which lowers your immune system
• allopurinol, a medicine used to treat gout
• hydrochlorothiazide, a medicine used to reduce excess fluid
• phenobarbitone and phenytoin, medicines used to treat epilepsy
• corticosteroids such as prednisone
• barbiturates, benzodiazepines and chloral hydrate, medicines used to help you relax or sleep
• chloramphenicol, a medicine used to treat serious bacterial infections
• sulphaphenazole, a medicine used to treat bacterial infections
• chloroquine, a medicine used to treat malaria
• imipramine, a medicine used to treat depression
• phenothiazines, medicines used to treat nausea, vomiting, psychotic disorders, depression and anxiety
• potassium iodide, a medicine used to treat fungal infections and iodine deficiency disorders
• vitamin A
• digoxin, a medicine used to treat irregular heartbeat
• medicines used in general anaesthesia
• indomethacin, a medicine used to relieve pain, swelling and other symptoms of inflammation, including arthritis
• medicines given to control diabetes
• vaccines, medicines used to prevent diseases
• anticoagulants such as warfarin used to thin out the blood
• medicines used in the treatment of cancer such as anthracyclines (doxorubicin) and busulfan.

These medicines may be affected by CYCLONEX or they may affect how well CYCLONEX works. You may need different amounts of your medicine, or you may need to take different medicines. Your doctor will advise you.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while taking CYCLONEX.

How to take CYCLONEX

When it is given

It is advisable that you take your dose in the morning.

How much to take

Your doctor will decide what dose you will receive. This depends on your condition and other factors, such as your weight, kidney function and the effect on your bone marrow of any previous treatment you may have had with x-ray or chemotherapy medicines.

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

How to take it

Take the tablets exactly as instructed by your doctor.

Always read the pharmacist’s label to check the exact dose and how often to take it.

Only take your dose on the days agreed with your doctor or pharmacist. The dose depends on the condition this medicine is being used for.

Take the tablets at about the same time of day.

Taking the tablets at the same time of day will have the best effect. It will also help you to remember when to take the medicine.

How long to take it

Your doctor will decide how long to continue your treatment with CYCLOBLASTIN.

If you forget to take it

If you forget to take a dose, ask your doctor for advice.

Do not use a double dose to make up for the dose that you missed.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 131 126) or go to accident and emergency at your nearest hospital, if you think you or anyone else may have taken too much CYCLONEX. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of a CYCLONEX overdose include the side effects listed below in the ‘Side Effects’ section but are usually of a more severe nature.

While you are taking CYCLONEX

Things you must do

Drink plenty of fluids before taking your medication and for 24 hours after you’ve taken your medication.

Empty your bladder frequently, especially for 24 hours after you’ve taken your medication.

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.

Tell all doctors, dentists and pharmacists who are treating you that you are having treatment with CYCLONEX.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are having treatment with CYCLONEX.

If you plan to have surgery that needs a general anaesthetic, it is very important you tell your doctor or dentist that you are having treatment with CYCLONEX.

If you become pregnant while you are having treatment with CYCLONEX, tell your doctor immediately.

Avoid grapefruit and grapefruit juice. Grapefruit contains a substance that can reduce the effect of CYCLONEX.

Avoid drinking alcohol while taking CYCLONEX.

CYCLONEX 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 give CYCLOBLASTIN to anyone else, even if they have the same condition as you.

Do not use CYCLONEX to treat any other complaints unless your doctor tells you to.

Avoid any contact with CYCLONEX tablets. Contact with the skin or eyes should be treated immediately by washing the affected area with water or sodium bicarbonate solution. Seek medical attention.

Things to be careful of

Be careful driving or operating machinery until you know how CYCLONEX affects you. As with other antineoplastic medicines, CYCLONEX may cause dizziness and tiredness in some people. Make sure you know how you react to CYCLONEX 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, the dizziness may be worse.

Possible side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are being treated with CYCLONEX. Like other medicines that treat cancer, CYCLONEX may have unwanted side effects, some of which may be serious. You may need medical treatment if you get some of the side effects.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:

• runny or blocked nose; sneezing, facial pressure or pain (rhinitis)
• headache
• dizziness, nausea, vomiting
• loss of appetite (anorexia)
• stomach pain or discomfort
• diarrhoea or constipation
• irregular or no menstrual periods
• unusual hair loss or thinning; hair becoming coarse
• darkening of skin; dry skin
• nail changes; darkening of the fingernails
• skin rash
• sudden reddening of the face and neck
• red, itchy rash on the back of the hands, palms and or feet
• recurrent, short periods of blurred vision.

Tell your doctor or nurse as soon as possible if you notice any of the following:

• mouth ulcers
• sore mouth
• yellowing of the skin and/or eyes (jaundice)
• changes to breathing
• gout - painful swollen joints
• painful urination; increased frequency of urination
• sudden weight change; build-up of fluid around the stomach.

These may be serious side effects. You may need medical attention.

Tell your doctor or nurse immediately, or go to Accident and Emergency at your nearest hospital, if any of the following happen:

• sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing (anaphylactic reaction);
• symptoms of bone marrow suppression (a disease of the blood where red and white blood cell numbers are reduced). These include tiredness, headaches, dizziness, being short of breath when exercising, looking pale, frequent infections, fever, severe chills, sore throat or mouth ulcers, bleeding or bruising more easily than normal, nose bleeds.
• diarrhoea with red blood and mucus, pain and fever (haemorrhagic colitis)
• severe diarrhoea
• blood in the urine
• lower abdominal pain
• chest pain
• altered heartbeat
• fits
• dizziness.

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

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

Do not be alarmed by this list of possible side effects. You may not experience any of them.

The benefits and side effects of CYCLONEX may take some time to occur. Therefore, even after you have finished your CYCLONEX treatment you should tell your doctor immediately if you notice any of the side effects listed in this section.

After treatment with CYCLONEX

Storage

Keep your medicine in its original packaging until it is time to take it.

If you take your medicine out of its original packaging it may not keep well.

Keep tablets in a cool dry place where the temperature will stay below 25°C and protected from light.

Do not store CYCLONEX tablets or any other medicines in a bathroom or near a sink.

Do not leave it in the car or on windowsills. Heat and dampness can destroy some medicines.

Keep CYCLONEX tablets where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Product description

What it looks like

CYCLONEX 50 mg film coated tablets are brown to pinkish and have a round convex shape.

The tablets are supplied in Al/Al blister packs, containing 50 tablets.

Ingredients

Each tablet contains 50 mg of cyclophosphamide, as the active ingredient.

The tablets also contain the following inactive ingredients:

• cellulose-microcrystalline
• lactose monohydrate
• croscarmellose sodium
• magnesium stearate
• colouring agent Opadry Pink.

This medicine is gluten-free and sucrose free.

Australian Registration Number

CYCLONEX 50 mg tablets can be identified by the Australian Register Number on the carton label: AUST R 297901

Sponsor

Supplied in Australia by:

Zenex Pharmaceuticals Pty Ltd
Level 6, 141 Flinders Lane
Melbourne, Victoria 3000
Australia

For medical enquiries call 1800 931 986.

This leaflet was revised in May 2020.

® Registered Trademark

Published by MIMS July 2020

1 Name of Medicine

Cyclophosphamide.

2 Qualitative and Quantitative Composition

Each tablet contains cyclophosphamide monohydrate equivalent to 50 mg cyclophosphamide.
The tablets contain the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, magnesium stearate and Opadry complete film coating system 21F240000 Pink (ARTG PI no: 111547).

Excipients with known effect.

3 Pharmaceutical Form

Cyclophosphamide tablets 50 mg.

4 Clinical Particulars

4.1 Therapeutic Indications

The proper use of cyclophosphamide requires accurate diagnosis, careful assessment of the anatomic extent of the disease, knowledge of the type and effects of any previous therapy and continued evaluation of the patient's general and haematological status. It is essential that adequate clinical and laboratory facilities be available for proper monitoring of patients during treatment with cyclophosphamide. The clinical course of the disease should be recorded in objective terms before treatment is begun and thereafter at regular intervals. Careful management of patients receiving cyclophosphamide will help achieve maximum benefit with minimum risk.

Antineoplastic properties.

Stage I.

Stage II.

Stage III.

Stage IV.

Immunosuppressive properties.

4.2 Dose and Method of Administration

Antineoplastic therapy.

Induction therapy.

Maintenance therapy.

Immunosuppressive therapy.

Impaired renal function.

4.3 Contraindications

Cyclophosphamide is contraindicated in:
Patients who have demonstrated a previous hypersensitivity to it.
The presence of active infections, which may lead to fatal complications as a result of immunosuppression induced by the cytotoxic treatment.
Patients with evidence of cystitis, acute systemic or urinary infection, urinary outflow obstruction, drug or radiation induced haemorrhagic cystitis.
Patients with severely depressed bone marrow function, particularly in patients who have been pre-treated with cytotoxic agents and/or radiotherapy.
The first trimester of pregnancy.
Cyclophosphamide therapy should not be commenced for 4 to 8 days after major surgery.

4.4 Special Warnings and Precautions for Use

Although toxic effects are likely to be related (in frequency and severity) to dose and/or frequency of drug administration, toxicity can occur at all doses. Patients should be fully informed by the attending physician of the risk of toxicity before undergoing cyclophosphamide treatment.
Routine baseline assessment should include a complete blood cell count and hepatic and renal function tests.
The following protective recommendations are given due to the toxic nature of this substance:
personnel should be trained in good technique for handling;
pregnant staff should be excluded from working with this drug;
all items used for administration or cleaning, including gloves, should be placed in high risk, waste disposal bags for high temperature incineration;
accidental contact with the skin or eyes should be treated immediately by copious lavage with water or sodium bicarbonate solution; medical attention should be sought.
Cyclophosphamide should be given cautiously to patients with any of the following conditions:
1. Leucopoenia.
2. Thrombocytopenia.
3. Tumour cell infiltration of bone marrow.
4. Previous X-ray therapy or radiotherapy.
5. Previous therapy with other cytotoxic agents.
6. Impaired hepatic function.
7. Impaired renal function.
Cyclophosphamide should be used with caution in compromised or elderly patients. Patients prone to infection, such as those with a weakened immune system and those with diabetes mellitus, should be closely observed.
Before starting treatment, it is necessary to exclude or correct any obstructions of the efferent urinary tract, cystitis, infections and electrolyte imbalances.
It is ordinarily advisable to inform patients in advance of possible alopecia, a frequent complication of cyclophosphamide therapy. Regrowth of hair can be expected, although occasionally the new hair may be of different colour or texture. The skin and fingernails may become darker during therapy. Nonspecific dermatitis has been reported to occur with cyclophosphamide.

Monitoring.

Mutagenic potential.

Oncogenic potential and secondary neoplasia.

Adrenalectomised patients.

Haemorrhagic cystitis.

Secondary infection.

Haematopoietic system.

Heart disorders.

Secondary tumours.

Hyperuricaemia.

General.

Use in hepatic impairment.

Use in renal impairment.

Use in the elderly.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Cyclophosphamide is often used in combination with other cytotoxic drugs or immunosuppressant agents having similar pharmacological effects. Under these circumstances additive toxicity may be expected and dose adjustment may be required, especially with regard to bone marrow depression/fostering of infection, gastrointestinal, kidney and heart toxicity.
Mesna (sodium 2-mercaptoethanesulfonate) is a synthetic sulfhydryl compound that can chemically interact with urotoxic metabolites of cyclophosphamide (e.g. acrolein) thought to be principally responsible for drug-induced haematuria and haemorrhagic cystitis. The concomitant administration of mesna not only contributes to the detoxification from these metabolites but also exerts uroprotective activity.
Simultaneous treatment with cyclophosphamide and allopurinol or hydrochlorothiazide increases the risk for bone marrow depression. This is probably due to decreased clearance of active metabolites of cyclophosphamide.
The rate of metabolism and the leucopoenia activity of cyclophosphamide are reportedly increased by chronic administration of high doses of phenobarbitone.
The concomitant administration of corticosteroids, such as prednisone, may also inhibit the activation of cyclophosphamide; this effect has however been reported as temporary since after long-term treatment the rate of activation has been increased.
Barbiturates and other drugs which induce liver microsomal enzymes, such as phenytoin, benzodiazepines and chloral hydrate may result in an increased pharmacological effect and increased toxicity of cyclophosphamide because of increased conversion of the drug to active (alkylating) metabolites.
Conversely, the concurrent use of inhibitors of microsomal enzyme activity in the liver, such as chloramphenicol, sulphaphenazole, chloroquine, imipramine, phenothiazines, potassium iodide and vitamin A may decrease the effects of cyclophosphamide.
Possible interaction between cyclophosphamide and digoxin yielding to cardiac arrhythmias has been reported during combination chemotherapy in a patient with atrial fibrillation previously well controlled with digoxin.
Cyclophosphamide may potentiate anthracycline-induced cardiotoxicity. An increased cardiotoxic effect may occur after radiotherapy of the cardiac region.
Cyclophosphamide treatment, which causes a marked and persistent inhibition of cholinesterase activity, potentiates the effect of succinylcholine chloride. If a patient has been treated with cyclophosphamide within ten days of planned general anaesthesia, the anaesthesiologist should be alerted.
Cyclophosphamide leads to a potentiation of the action of suxamethonium and may lead to prolonged apnoea.
In one report, a patient with multiple myeloma treated with low dose intravenous cyclophosphamide developed acute life-threatening hyponatraemia after receiving concurrent oral indomethacin.
Cyclophosphamide also interacts with anticoagulants and insulin. When other oral hypoglycaemic agents are given with cyclophosphamide, the reduction in blood sugar levels may be potentiated.
Due to its immunosuppressive activity, patients may have a diminished response to any vaccination; administration of activated vaccines may be accompanied by a vaccine-induced infection.
In general, patients receiving cyclophosphamide should refrain from drinking alcohol.
Grapefruit contains a compound that may impair the activation of cyclophosphamide, thereby reducing efficacy. Patients should avoid grapefruit and grapefruit juice.
Laboratory values which can be altered by cyclophosphamide in addition to those mentioned above are the skin tests for Candida, mumps, Trichophyton and tuberculin (which may give false-negative results) and the Papanicolaou test (which may give false-positive results).

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

4.7 Effects on Ability to Drive and Use Machines

Due to the possibility of side effects that might result in circulatory deficiencies e.g. nausea and vomiting, the physician should determine the individual patient's ability to drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

General.

Haematopoietic.

Gastrointestinal.

Genitourinary.

Hepatic.

Dermatological.

Respiratory.

Cardiac toxicity.

Secondary neoplasia.

Metabolic.

Reproductive system.

Wound healing.

Inappropriate water retention.

Reporting suspected adverse effects.

4.9 Overdose

The most serious consequence of overdosage are myelosuppression (particularly granulocytopenia), and haemorrhagic cystitis. Bleeding, possibly severe, may occur from the bladder and gastrointestinal tract.
Profound myelosuppression may require such measures as blood transfusions, antibiotic therapy, colony stimulating factors (G-CSF, GM-CSF) and reverse barrier nursing. Consider administration of activated charcoal in the event of a potentially toxic ingestion. Activated charcoal is most effective when administered within 1-hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected. In all cases, forced alkaline diuresis with copious fluid intake, using diuretics if necessary, should be employed. Patients should be observed for signs of water overload and monitored for electrolyte disturbances. Haemodialysis may be of benefit when traditional measures are ineffective.
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.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Protein binding.

Distribution.

Metabolism.

Half life.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinogenicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

See Section 2 Qualitative and Quantitative Composition.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Store below 25°C, protect from light.

6.5 Nature and Contents of Container

The tablets are supplied in PA/Al/PVC/Al blister packs, containing 50 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.

CAS number.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription Only Medicine.

Summary Table of Changes