SUMMARY CMI

Mitocin

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why have I been given Mitocin?

Mitocin contains the active ingredient mitomycin. Mitocin is used to treat advanced cancers. Mitocin is used to prevent recurrent bladder cancer. For more information, see Section 1. Why have I been given Mitocin? in the full CMI.

2. What should I know before I am given Mitocin?

Do not receive Mitocin if you have ever had an allergic reaction to mitomycin or any of the ingredients listed at the end of the CMI. Do not receive Mitocin if you have an acute infection, low white or red blood cell counts or platelet counts, any condition or any blood disorder which causes you to bleed very easily, or you are breastfeeding. Do not receive Mitocin in the bladder if you have a perforated bladder.

Talk to your doctor if you have any other medical conditions, take any other medicines, you are pregnant or plan to become pregnant or are breastfeeding, you are a woman of childbearing potential or a man capable of fathering children, or you are elderly.

For more information, see Section 2. What should I know before I am given Mitocin? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Mitocin and affect how it works. See Section 3. What if I am taking other medicines? in the full CMI.

4. How Mitocin is given?

• Mitocin is given to you in hospital.as an injection into your vein or directly into the bladder. It will always be given by a doctor or a nurse.
• The amount (dose) you will be given depends on a variety of factors including your size, the type of cancer and any other chemotherapy you are receiving. Your doctor will work out the right dose for you and how often you should be given Mitocin.

More information can be found in Section 4. How Mitocin is given? in the full CMI.

5. What should I know while being given Mitocin?

For more information, see Section 5. What should I know while being given Mitocin? in the full CMI.

6. Are there any side effects?

Common side effects include, nausea, vomiting, rash, cough, difficulty breathing, shortness of breath. Serious side effects include allergic reactions with symptoms such as, swelling of the face, tongue or other parts of the body, problems with breathing, coughing, dizziness, flushing and sweating. Other serious side effects include problems with bleeding such as, bruising easily and bleeding longer than usual; fever, confusion, fast heartbeat, and rapid breathing associated with infection.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

FULL CMI

Mitocin

Active ingredient: mitomycin

Consumer Medicine Information (CMI)

This leaflet provides important information about using Mitocin. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Mitocin.

Where to find information in this leaflet:

1. Why have I been given Mitocin?
2. What should I know before I am given Mitocin?
3. What if I am taking other medicines?
4. How Mitocin is given?
5. What should I know while being given Mitocin?
6. Are there any side effects?
7. Product details

1. Why have I been given Mitocin?

Mitocin contains the active ingredient mitomycin.

Mitomycin is an anticancer agent.

Mitocin is used to treat cancer of the stomach, pancreas, colon, lung (non-small cell), breast, cervix, head and neck, liver and bladder. It works by stopping cancer cells from growing.

2. What should I know before I am given Mitocin?

Warnings

Do not receive Mitocin if:

• you are allergic to mitomycin, or any of the ingredients listed at the end of this leaflet.
• Always check the ingredients to make sure you can use this medicine.

Do not receive Mitocin intravenously if:

• you are breastfeeding.
• you have low red or white blood cell counts.
• you have low platelet counts.
• you have an acute infection.
• you have any condition or any blood disorder which causes you to bleed very easily.

Do not receive Mitocin in the bladder (intravesically) if:

• you have perforation (hole) of the bladder.

Check with your doctor if you:

• have any other medical conditions including those listed below:
  - you have ever had an allergic reaction to any medicine, or other substances such as food, preservatives or dyes.
  - you have ever had a condition which caused you to bleed very easily.
  - you have an infection now or had one recently.
  - you have a problem with your kidneys.
  - you have a problem with your liver.
  - you have a problem with your lungs.
  - your general state of health is poor.
  - you have inflammation of the bladder, and you are receiving Mitocin in the bladder.
  - you are undergoing radiotherapy.
• take any medicines for any other condition.

Before you start treatment, your doctor may arrange kidney, liver, lung, and blood tests. Be sure to keep your appointments.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed. Mitocin should not be used during breastfeeding. Breast-feeding must be discontinued before you start to use Mitocin.

3. What if I am taking other medicines?

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

Check with your doctor if you are not sure about what medicines, vitamins or supplements you are taking and if these affects or are affected by Mitocin.

4. How Mitocin is given?

Mitocin is given to you in hospital. It will always be given to you by a doctor or by a nurse.

How much is given

• The amount (dose) you will be given is worked out by your doctor. It is based on a variety of factors including, your size, the type of cancer, and any other chemotherapy you are receiving. The dose worked out for you may be different to the dose for another patient.

How it is given

• Mitocin is mixed with an intravenous fluid and given as an infusion (drip) into a vein. It may be given as a single dose, or divided into 10 daily doses given each day for five days then after 2 treatment-free days, given for another 5 five days. This may all be repeated at intervals of 6 to 8 weeks.
• Mitocin may also be given directly into the bladder via a small tube and retained in the bladder for as long as possible, until you urinate.

If you are given too much Mitocin

Mitocin will be given to you under the supervision of a doctor so it is unlikely that you will receive too much.

If you think that you have been given too much Mitocin, you may need urgent medical attention.

You should immediately:

• phone the Poisons Information Centre
  (by calling 13 11 26), or
• contact your doctor, or
• go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while being given Mitocin?

Things you should do

• Be sure to keep all your doctor's appointments so your progress can be checked
  You will require blood tests to see how Mitocin is affecting your blood, particularly your white blood cell and platelet counts, or if it is affecting any organs such as your kidneys. If the numbers of white cells or platelets in your blood are significantly reduced, your doctor may reduce the amount of Mitocin you are given or may stop treatment until the numbers of white cells and/or platelets increase. Mitocin can affect your white cell count for up to 8 weeks after you received your Mitocin.
• Due to the effect on your blood cells, 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.
• If you intend to breastfeed while being treated with Mitocin, tell your doctor.
• If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being given Mitocin.

Tell your doctor or nurse if you have any concerns before during or after your treatment with Mitocin.

Tell any other doctors, dentists or pharmacists who are treating you that you are being given Mitocin.

If you are about to be started on any new medicine, tell your doctor, dentist or pharmacist that you are being given Mitocin.

If you plan to have surgery that needs a general anaesthetic, tell your doctor or dentist that you are being given Mitocin, or have been given Mitocin within the last 12 months.

If you become pregnant or intend to become pregnant while being treated with Mitocin, tell your doctor.

Remind any doctor, dentist or pharmacist you visit that you have been given Mitocin.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Mitocin affects you.

As with other medicines used to treat cancer Mitocin may cause tiredness, drowsiness and blurring of vision in some people.

Make sure you know how you react to Mitocin before you drive a car, operate machinery, or do anything else that could be dangerous if you are tired or drowsy. If this occurs do not drive.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or nurse if you have any further questions about side effects.

Some of these side effects may be prevented or treated by therapy with other medicines. If side effects do occur, their severity usually depends on the dose of Mitocin you have received.

Less serious side effects

Serious side effects

Tell your doctor if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Mitocin contains

Do not take this medicine if you are allergic to any of these ingredients.

Before being given to you Mitocin will be dissolved in sterile water and added to an intravenous fluid.

For intravesical administration, Mitocin will be dissolved in sterile water or a sterile saline solution.

What Mitocin looks like

Mitocin is a blue-violet powder in a vial (Aust R 370360).

Who distributes Mitocin

Echo Therapeutics Pty Ltd
1-2 Kochia Lane
Lindfield NSW 2070

This leaflet was prepared in 25 July 2022.

Published by MIMS September 2022

1 Name of Medicine

Mitomycin.

2 Qualitative and Quantitative Composition

Mitocin injection is available in single use vials. Each vial contains 20 mg of mitomycin.
One vial of Mitocin 20 mg powder for injection/infusion or intravesical use contains 20 mg of mitomycin. After reconstitution with 40 mL water for injections 1 mL of solution for injection/infusion contains 0.5 mg mitomycin. After reconstitution with 20 mL solvent 1 mL of solution for intravesical use contains 1 mg mitomycin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Powder for injection/infusion or intravesical use.
Mitocin is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have anti-tumour activity. Mitomycin is a blue-violet crystalline powder slightly soluble in water, freely soluble in dimethylacetamide, sparingly soluble in methanol, slightly soluble in acetone.

4 Clinical Particulars

4.1 Therapeutic Indications

Mitomycin is indicated in the palliative treatment of carcinoma of the stomach, pancreas, colon, lung (non-small cell), breast, cervix, head and neck, liver and bladder.

4.2 Dose and Method of Administration

Mitocin is administered by slow intravenous infusion. Mitocin should not be given by rapid intravenous injection.
Mitocin is for single use in one patient only. Discard any unused portion.
Mitocin should be given intravenously only, using care to avoid extravasation of the compound. If extravasation occurs, cellulitis, ulceration and slough may result.
Each vial contains mitomycin 20 mg. To administer, add sterile water for injection 20 mL to 20 mg vials. Shake to dissolve. The reconstituted solution is then added immediately as a single dose through a running intravenous infusion of 5% glucose, 0.9% sodium chloride or sodium lactate injection IV infusion, for the treatment of all tumours other than bladder tumours. Shake until the reconstituted solution becomes clear and free of particles.
For the treatment of bladder tumours the reconstituted 20 mg dose is further diluted to 50 mL with sterile water for injection and immediately instilled directly into the bladder via a catheter and retained in the bladder as long as possible.
After full haematological recovery (see Guide to dosage adjustment) from any previous chemotherapy, either of the following dosage schedules may be used at 6 to 8 week intervals. Because of cumulative myelosuppression, patients should be fully re-evaluated after each course of Mitocin and the dose reduced if the patient has experienced any toxicities. Doses greater than 20 mg/m² have not been shown to be more effective, and are more toxic than lower doses. Dosage reduction should be considered in cases with prior extensive bone marrow irradiation or renal dysfunction.
1. 20 mg/m² intravenously as a single dose via a functioning intravenous catheter.
2. 2 mg/m²/day intravenously for 5 days. After a drug-free interval of 2 days, 2 mg/m²/day for 5 days, thus making the total initial dose 20 mg/m² given over 10 days. The following schedule (Table 1) is suggested as a guide to dosage adjustment.
No repeat dosage should be given until leucocyte count has returned to 3,000 and platelet count to 75,000.
Renal and hepatic dysfunction also usually require dosage reduction and may be an indication for interrupting treatment. When Mitocin is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly. If the disease continues to progress after two courses of Mitocin, the drug should be stopped since chances of response are minimal.

Guidelines for proper handling and disposal of anticancer drugs.

4.3 Contraindications

Pancytopenia or isolated leucopoenia/thrombopenia, haemorrhagic diathesis and acute infections are absolute contraindications.
Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.
Breastfeeding.
Mitomycin is contraindicated in patients with coagulation disorder.

Systemic therapy.

Intravesical therapy.

4.4 Special Warnings and Precautions for Use

Mitomycin should not be administered orally, intrathecally or into the tissues (such as intramuscularly or subcutaneously).
Mitomycin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when diagnostic and treatment facilities are readily available.
Mitomycin should only be used when appropriate access to haematological and pathological services is available. Haematological screening is required during therapy and for at least 7 weeks after treatment.
Patients being treated with mitomycin must be observed carefully and frequently during and after therapy.
The use of mitomycin results in a high incidence of bone marrow suppression, particularly thrombocytopenia and leucopenia. Thrombocytopenia may contribute to hemorrhage and leucopenia to overwhelming infections in already compromised patient (see Section 4.8 Adverse Effects (Undesirable Effects)). Therefore, the following studies should be obtained repeatedly during therapy and for at least 7 weeks following therapy: platelet count, white blood cell count, differential and haemoglobin. The occurrence of a platelet count below 100,000 or a WBC below 4,000, or a progressive decline in either is an indication for interruption of therapy.
Patients should be advised of the potential toxicity of this drug, particularly bone marrow suppression. Deaths have been reported due to septicaemia as a result of leucopenia due to the drug.
Dose adjustment according to nadir count may be required. Therefore, the following studies should be obtained repeatedly during therapy and for at least 8 weeks following therapy: white blood cell (WBC) and platelet counts, differential and hemoglobin. The occurrence of a platelet count below 100,000/mm³ or a WBC below 4,000/mm³ or a progressive decline in either is an indication to withhold further therapy until blood counts have recovered above these levels.
Hemolytic Uremic Syndrome (HUS), a serious complication of chemotherapy, consisting primarily of microangiopathic haemolytic anemia, thrombocytopenia, and irreversible renal failure, has been reported in patients receiving systemic mitomycin. The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs; however, most cases occur at doses > 60 mg of mitomycin. Blood product transfusion may exacerbate the symptoms associated with this syndrome. The incidence of the syndrome has not been defined (see Section 4.8 Adverse Effects (Undesirable Effects)).
Patients receiving mitomycin should be observed for evidence of renal toxicity. Mitomycin should not be given to patients with a serum creatinine greater than 1.7 mg percent.
Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of this acute respiratory distress has occurred within minutes to hours after the vinca alkaloid injection. The total number of doses for each drug has varied considerably. Bronchodilators, corticosteroids and/or oxygen have produced symptomatic relief (see Section 4.8 Adverse Effects (Undesirable Effects)).
A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapeutic agents who were being maintained perioperatively at FiO₂ concentrations greater than 50% (see Section 4.8 Adverse Effects (Undesirable Effects)). Therefore, caution should be exercised, and only enough oxygen to provide adequate arterial saturation should be used since oxygen itself can be toxic to the lungs. Careful attention should be paid to fluid balance, and overhydration should be avoided.
Reports of bladder fibrosis/contraction, following intravesicular administration, which in rare cases have required cystectomy, have been received post marketing. Bladder necrosis and penile necrosis have also been reported (see Section 4.8 Adverse Effects (Undesirable Effects)).
Injection site reactions may occur during the administration of mitomycin (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.

Paediatric use.

Effects on laboratory tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No data available.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

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)

Bone marrow toxicity.

Integument and mucous membrane toxicity.

Renal toxicity.

Pulmonary toxicity.

Haemolytic uremic syndrome (HUS).

Hepatic toxicity.

Cardiac.

Acute side effects due to mitomycin.

Intravesical administration.

Reporting suspected adverse effects.

4.9 Overdose

No specific antidote for mitomycin is known. Management of overdose should include general supportive measures to sustain the patient through any period of toxicity that may occur.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mitomycin is an antibiotic isolated from Streptomyces caespitosus with anti-neoplastic effect. It is present in an inactive form. Activation to a trifunctional alkylating agent is rapid, either at physiological pH in the presence of NADPH in serum or intracellularly in virtually all cells of the body with the exception of the cerebrum, as the blood-brain barrier is not overcome by mitomycin. The 3 alkylating radicals all stem from a quinone, an aziridine and a urethane group.

Mechanism of action.

Clinical trials.

5.2 Pharmacokinetic Properties

Absorption.

Distribution.

Metabolism.

Excretion.

5.3 Preclinical Safety Data

Genotoxicity.

Carcinotoxicity.

6 Pharmaceutical Particulars

6.1 List of Excipients

Mannitol.

6.2 Incompatibilities

Incompatibilities occur with highly acidic or alkaline substances. The optimum pH of the ready-to-use mitomycin solution is 7.0.

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.

Reconstituted solution.

6.4 Special Precautions for Storage

Store between 15°C-25°C. Store the vial in the outer carton in order to protect from light. For storage conditions after reconstitution of the medicinal product, see Section 6.3 Shelf Life.

6.5 Nature and Contents of Container

Each 20 mg vial contains 20 mg mitomycin and 40 mg mannitol. Each pack contains 1 vial.
The powder is stored in a 50 mL amber glass vial (glass type I Ph. Eur.), closed with a grey bromobutyl stopper and sealed with a white flip-off aluminium seal.

6.6 Special Precautions for Disposal

Special precautions for the preparation and the disposal of unused cytotoxic medicinal products should be complied with.
The reconstituted solution should be stored away from light in the refrigerator.
Before the ready-to-use solution is used it should be warmed up to room or body temperature.

6.7 Physicochemical Properties

The CAS number for Mitomycin is 50-07-7. The structure is:
[(1aS,8S,8aR,8bS)-6-Amino-8a-methoxy-5-methyl-4,7-dioxo-,1a,2,4,7,8,8a,8boctahydroazirino [2',3':3,4] pyrrolo[1,2-a]-indol-8-yl]methyl carbamate.
Molecular weight: 334.3. Molecular formula: C₁₅H₁₈N₄O₅.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes