Consumer medicine information

MITOMYCIN OMEGAPHARM

Mitomycin

BRAND INFORMATION

Brand name

Mitomycin Omegapharm

Active ingredient

Mitomycin

Schedule

What is in this leaflet

This leaflet answers some of the common questions about Mitomycin Omegapharm but 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 treating you with Mitomycin Omegapharm against the benefits they expect it will have for you.

If you have any concerns about being treated with Mitomycin Omegapharm ask your doctor or pharmacist.

Keep this leaflet, because you may need to read it again.

What Mitomycin Omegapharm is used for

Mitomycin Omegapharm contains mitomycin, which is an anti-cancer agent. It is used to treat cancer of the stomach, pancreas, colon, lung (non-small cell), breast, cervix, head and neck, liver and bladder.

Mitomycin Omegapharm works by stopping cancer cells from growing.

Ask your doctor if you have any question about why Mitomycin Omegapharm was prescribed for you.

Before you are given Mitomycin Omegapharm

When you must not be given Mitomycin Omegapharm

You must not take Mitomycin Omegapharm if you have a history of severe allergic reactions to mitomycin or to any of the ingredients listed at the end of this leaflet.

Symptoms of a severe allergic reaction may include; chills, fever, fast heart beat, wheezing or coughing, difficulty breathing, dizziness, flushing, sweating and swelling of the face, tongue or other parts of the body. You must not take Mitomycin Omegapharm if you have any condition or any blood disorder which causes you to bleed very easily.

Before you are given Mitomycin Omegapharm

You must tell your doctor if;

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 ever had a problem with your kidneys.
you are pregnant or likely to become pregnant you are breast-feeding.

Taking other medicines

You must tell your doctor if you are taking any medicines, Including the ones you buy without a prescription from a pharmacy, supermarket or health food shop. The medicines you take may be affected by Mitomycin Omegapharm, or may affect how well it works. You may need different amounts of your medicine, or you may need to take or use different medicines. Your doctor will advise you, they may have more information on medicines to be careful with or avoid while you are being given Mitomycin Omegapharm.

How Mitomycin Omegapharm is given

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

Mitomycin Omegapharm may be given alone or with other anti-cancer medicines.

How much is given

The amount (dose) you will be given is worked out by your doctor. It is based on your size and on the type of cancer. The dose worked out for you may be different to the dose for another patient.

How it is given

Mitomycin Omegapharm 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.

Mitomycin Omegapharm 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.

Overdose

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

However if you experience severe side effects you must tell your doctor or a nurse immediately. You may need urgent medical attention.

While you are being given Mitomycin Omegapharm

Things you must do

Be sure to keep all your doctor’s appointments so your progress can be checked. You will require blood tests to see how Mitomycin Omegapharm is affecting your blood, particularly your white cell count, or if it is affecting any other organs such as your kidneys or liver. If the numbers of white cells in your blood are significantly reduced, your doctor may reduce the amount of Mitomycin Omegapharm you are given or may stop treatment until the numbers of white cells increase.

Mitomycin Omegapharm can affect your white cell count for up to 8 weeks after you received your Mitomycin Omegapharm.

Due to the effect on your blood cells, the following precautions should be taken to reduce your risk if 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.

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

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

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

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

If you become pregnant while being treated with Mitomycin Omegapharm, tell your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how being treated Mitomycin Omegapharm affects you.

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

Make sure you know how you react to Mitomycin Omegapharm 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.

Side effects

Tell your doctor or a nurse as soon as possible if you do not feel well while you are being given Mitomycin Omegapharm.

Like other cancer medicines, Mitomycin Omegapharm helps most people who have cancer, but it may have unwanted 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 Mitomycin Omegapharm you have received.

Ask your doctor to answer any questions you may have.

Tell your doctor or nurse if you notice any of the following and they worry you.

fever, loss of appetite, nausea, vomiting, diarrhoea
headache, blurred vision, confusion, tiredness,
irregular heart beat (palpitations), fatigue
oedema, pain, swelling
When administered into the bladder, side effects may include irritation of the bladder, change in the frequency of urination, itchy rash on the hands and genital area, bladder damage, skin damage to the genital area.

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

tiredness, headaches, shortness of breath when exercising, dizziness, looking pale, fast heart rate
infection; fever, chills, sore throat, bruising easily, bleeding longer than usual after minor cuts or scrapes, bleeding gums or nose bleeds, rash of small reddish-purple spots on your skin, blood in your stool, urine or vomit
passing little or no urine, drowsiness, nausea, vomiting, poor appetite, headache, weakness, fever, diarrhoea, irritable
nausea, vomiting, diarrhoea, abdominal pain, loss of appetite with yellowing of the skin and eyes, bleeding, fatigue, weakness, or confusion
burning, stinging, pain, redness or swelling at the injection site
Fatigue, fluid on the ankles or abdomen, shortness of breath, dry or moist cough

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

Tell your doctor immediately, or go to accident and emergency at your nearest hospital if you notice any of the following signs of a sudden life-threatening allergic reaction:

chills, fever, fast heart beat, wheezing or coughing, difficulty breathing, dizziness, flushing, sweating and swelling of the face, tongue or other parts of the body.

Tell your doctor if you notice any of these effects, or if you experience any other effects while being given Mitomycin Omegapharm.

What is in Mitomycin Omegapharm

The active ingredient in Mitomycin Omegapharm is mitomycin.

Each vial contains 2 mg, 10 mg, or 20 mg mitomycin.

The In-active ingredient in Mitomycin Omegapharm is mannitol.

Before being given to you Mitomycin Omegapharm will be dissolved in sterile water and added to an intravenous fluid. For intravesical administration, Mitomycin Omegapharm will also be dissolved in sterile water.

Registration Numbers:

Mitomycin Omegapharm 2 mg AUST R 243552

Mitomycin Omegapharm 10 mg AUST R 243553

Mitomycin Omegapharm 20 mg AUST R 243554

Last updated April 2016

Published by MIMS March 2017

BRAND INFORMATION

Brand name

Mitomycin Omegapharm

Active ingredient

Mitomycin

Schedule

Name of the medicine

Mitomycin C.

Excipients.

Mannitol 4 mg (2 mg vial), 20 mg (10 mg vial) or 40 mg (20 mg vial).

Description

Chemical name: [(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 formula: C₁₅H₁₈N₄O₅. MW: 334.3. CAS: 50-07-7. Mitomycin is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have antitumour activity. Mitomycin C is a blue-violet crystalline powder slightly soluble in water, freely soluble in dimethylacetamide, sparingly soluble in methanol, slightly soluble in acetone.
Mitomycin injection is available in single use vials.

Pharmacology

Mitomycin inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine correlates with the degree of mitomycin induced crosslinking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. In humans, mitomycin is rapidly cleared from the serum after intravenous administration. Time required to reduce the serum concentration by 50% after a 30 mg bolus injection is 17 minutes. After injection of 30 mg, 20 mg or 10 mg IV, the maximal serum concentrations were 2.4 microgram/mL, 1.7 microgram/mL and 0.52 microgram/mL respectively. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other issues as well. The rate of clearance is inversely proportional to the maximal serum concentration because, it is thought of saturation of the degradative pathways. Approximately 10% of a dose of mitomycin is excreted unchanged in the urine. Since metabolic pathways are saturated at relatively low doses, the percent of a dose excreted in urine increases with increasing dose. In children, excretion of intravenously administered mitomycin is similar.

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.

Contraindications

Mitomycin is contraindicated in patients who have demonstrated a hypersensitive or idiosyncratic reaction to it in the past.
Mitomycin is contraindicated in patients with thrombocytopenia, coagulation disorder, or an increase in bleeding tendency due to other causes.

Precautions

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 leukopenia. Thrombocytopenia may contribute to hemorrhage and leukopenia to overwhelming infections in an already compromised patient (see Adverse 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 4000, 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 leukopenia 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 4000/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 Adverse 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 Adverse 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 Adverse 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 postmarketing. Bladder necrosis and penile necrosis have also been reported. (See Adverse Effects.)
Injection site reactions may occur during the administration of mitomycin. (See Adverse 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 pregnancy.

(Category D)
Safe use of mitomycin in pregnant women has not been established. Teratological changes have been noted in animal studies. The effect of mitomycin on fertility is unknown.

Use in lactation.

It is not known if mitomycin is excreted in human milk. Because many drugs are excreted in milk, it is recommended that women receiving mitomycin not breast feed because of the potential for serious adverse reactions from mitomycin in nursing infants.

Animal toxicity.

Mitomycin toxicity is consistent in all species studied to date. In laboratory animals, the LD₅₀ varies from 1.0-2.5 mg/kg, which corresponds with severe toxicity in humans. In mice, rats, cats, dogs and monkeys, death from poisoning was delayed with the animals characteristically progressively losing weight and showing gastrointestinal disturbances. Frequently, death was associated with fever and leukopenia. In animals, oral toxicity was similar to intravenous toxicity at doses 8-12 times the intravenous doses. The LD₅₀ of multiple low intravenous doses in dogs was approximately equivalent to the LD₅₀ a single large intravenous dose. Mitomycin has been found to be carcinogenic in rats and mice. At doses approximating the recommended clinical dose in man, it produces a greater than 100 percent increase in tumour incidence in male Sprague-Dawley rats, and a greater than 50 per cent increase in tumour incidence in female Swiss mice.

Adverse Effects

Bone marrow toxicity.

This was the most common and most serious toxicity occurring in 605 of 937 patients (64.4%). Thrombocytopenia and/or leukopenia may occur anytime within 8 weeks after onset of therapy with an average time of 4 weeks. Recovery after cessation of therapy was within 10 weeks. About 25% of the leukopenia or thrombocytopenic episodes did not recover. Mitomycin produces cumulative myelosuppression.

Integument and mucous membrane toxicity.

This has occurred in approximately 4% of patients treated with mitomycin. Cellulitis at the injection site has been reported and is occasionally severe. The most important dermatologic event is necrosis and consequent sloughing of tissue which results if the drug is extravasated during injection. Extravasation may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood return when the injection needle is aspirated. There have been reports of delayed erythema and/or ulceration occurring either at or distant from the injection site, weeks to months after mitomycin, even when no obvious evidence of extravasation was observed during administration. Skin grafting has been required in some cases. Stomatitis and alopecia also occurred frequently. Rashes are rarely reported. Amputations subsequent to extravasation of mitomycin have occurred. (See Precautions.)

Renal toxicity.

2% of 1281 patients demonstrated a statistically significant rise in creatinine. There appeared to be no correlation between total dose administered or duration of therapy and the degree of renal impairment.

Pulmonary toxicity.

This has occurred infrequently but can be severe. Dyspnoea with a nonproductive cough and radiographic evidence of pulmonary infiltrates may be indicative of mitomycin induced pulmonary toxicity. If other aetiologies are eliminated, mitomycin therapy should be discontinued. Steroids have been employed as treatment of this toxicity, but the therapeutic value has not been determined. A few cases of adult respiratory distress syndrome have been reported in patients receiving mitomycin in combination with other chemotherapeutic agents and who were maintained at FiO₂ concentrations greater than 50% perioperatively. (See Precautions.)

Haemolytic uremic syndrome (HUS).

This serious complication of chemotherapy, consisting primarily of microangiopathic haemolytic anemia (haematocrit ≤ 25%), thrombocytopenia (≤ 100,000/mm³), and irreversible renal failure (serum creatinine ≥ 1.6 mg/dL or ≥ 140 micromol/L) has been reported in patients receiving systemic mitomycin. Microangiopathic haemolysis with fragmented red blood cells seen on peripheral blood smears has occurred in 98% of patients with the syndrome. Other less frequent complications of the syndrome may include pulmonary edema (65%), neurologic abnormalities (16%), and hypertension. Exacerbation of the symptoms associated with HUS has been reported in some patients receiving blood product transfusions. The incidence of the syndrome has not been defined. A high mortality rate (52%) has been associated with this syndrome. (See Precautions.)
The syndrome may occur at any time during systemic therapy with mitomycin as a single agent or in combination with other cytotoxic drugs. Less frequently, HUS has also been reported in patients receiving combinations of cytotoxic drugs not including mitomycin. Of 83 patients studied, 72 developed the syndrome at total doses exceeding 60 mg of mitomycin. Consequently, patients receiving ≥ 60 mg of mitomycin should be monitored closely for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function.

Hepatic toxicity.

Hepatic dysfunction has been reported in approximately 5% of cases.

Cardiac.

Congestive heart failure, often responding to conventional therapy, has been reported rarely. Almost all patients who experienced this side effect had received prior doxorubicin therapy.

Acute side effects due to mitomycin were.

Fever, anorexia, nausea and vomiting. They occurred in about 14% of 1281 patients.
Other undesirable side effects that have been reporting during mitomycin therapy have been headache, blurring of vision, confusion, drowsiness, syncope, fatigue, oedema, thrombophlebitis, haematemesis, diarrhoea and pain. These did not appear to be dose related and were not unequivocally drug related. They may have been due to the primary or metastatic disease processes.

Intravesical administration.

Genitourinary irritation, including dysuria, cystitis, nocturia, increased frequency of micturition, hematuria, and other symptoms of local irritation, rash and pruritus on hands and genital area. Reports of bladder fibrosis/ contraction, which in rare cases have required cystectomy, have been received postmarketing (see also Precautions). Bladder necrosis and penile necrosis have been reported following intravesical administration of mitomycin. (See Precautions.)

Dosage and Administration

Mitomycin is administered by slow intravenous infusion. Mitomycin should not be given by rapid intravenous injection.
Mitomycin is for single use in one patient only. Discard any unused portion.
Mitomycin 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 either mitomycin 2 mg, mitomycin 10 mg or mitomycin 20 mg. To administer add sterile water for injection 4 mL to the 2 mg vial, or 20 mL to the 10 mg and 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. If product does not dissolve immediately, allow to stand at room temperature until solution is obtained.
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 mitomycin 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 is suggested as a guide to dosage adjustment. See Table 1.
No repeat dosage should be given until leukocyte count has returned to 3000 and platelet count to 75,000.
Renal and hepatic dysfunction also usually require dosage reduction and may be an indication for interrupting treatment. When Mitomycin Omegapharm is used in combination with other myelosuppressive agents, the doses should be adjusted accordingly. If the disease continues to progress after two courses of Mitomycin Omegapharm, the drug should be stopped since chances of response are minimal.

Guidelines for proper handling and disposal of anticancer drugs.

Care must be taken whenever handling anticancer products. Always take steps to prevent exposure. This includes appropriate equipment, such as, wearing gloves, and washing hands with soap and water after handling such products.

Overdosage

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.

Presentation

Powder for injection, 2 mg, 10 mg*, 20 mg: 1's (single use vial).
*Not currently marketed in Australia.

Storage

1. Dry crystalline Mitomycin Omegapharm.

Stable for up to 2 years at store below 25°C. Protect from light.

2. Reconstituted with water for injection or (mitomycin concentration 0.5 mg/mL to 1 mg/mL).

Stable for 24 hours when protected from light and stored in a cool place. However, as the solution does not contain any preservative agent, to reduce the microbiological hazard, use as soon as practicable after reconstitution. If storage is necessary, hold at 2°-8°C for not more than 24 hours.

Note.

The solution contains no bacteriostat.

3. Stability in IV fluids at room temperature.

5% glucose should be used immediately.
Sodium lactate injection should be used immediately.
0.9% sodium chloride use within 6 hours.
To reduce the microbiological hazard, use as soon as practicable after dilution.

Poison Schedule

S4.

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