mitomycin

Trade Name:

Mutamycin® (generic brand available)

Synonym:

mitomycin C

MMC

Appearance:

Clear, light blue solution

Monograph Name:

mitomycin

Monograph Body:

Drug Monograph

A - Drug Name

mitomycin

SYNONYM(S): mitomycin C; MMC

COMMON TRADE NAME(S): Mutamycin® (generic brand available)

B - Mechanism of Action and Pharmacokinetics

Mitomycin is a purple antibiotic isolated from Streptomyces caespitosus. Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. RNA synthesis is also inhibited at higher mitomycin concentrations. Mitomycin is cell cycle phase-nonspecific.

Absorption

Oral absorption: Erratic

Not appreciably absorbed from the bladder

Distribution

Rapidly cleared from plasma. Highest concentraions found in kidney, followed by muscles, eyes, lungs, intestine and stomach. Found in ascites.

Cross blood brain barrier?

PPB

No information found

Metabolism

Prodrug activated in vivo, primary means of elimination is by hepatic metabolism, also metabolized by enzymes in kidneys, spleen, brain and heart; saturable at relatively low doses.

Active metabolites

yes

Inactive metabolites

yes

Elimination

Biphasic elimination. Excreted in urine, detected in bile and feces, biliary level may exceed plasma level.

Urine

10% excreted unchanged in urine, increases with increasing doses.

Half-life

17 minutes

C - Indications and Status

Health Canada Approvals:

Topical

Transitional cell bladder cancer (superficial), 1st or 2nd line

Systemic

Stomach cancer (palliative)
Colon cancer (palliative)

Other Uses:

Anal cancer
Vulvar cancer

D - Adverse Effects

Emetogenic Potential:

Low

Extravasation Potential: Vesicant

ORGAN SITE	SIDE EFFECT* (%)	ONSET**
Cardiovascular	Cardiotoxicity (rare, with prior anthracyclines)	E D
	Venous thromboembolism	E
Dermatological	Alopecia (frequent)	E
	Radiation recall reaction (rare)	I
	Rash (10%, generally on extremities)	I E
Gastrointestinal	Anorexia	E
	Diarrhea	E
	Mucositis (4%)	E
	Nausea, vomiting	I
General	Edema	E
	Fatigue	E
	Pain	E
Hematological	Hemolytic uremic syndrome (rare)	D
	Myelosuppression ± infection, bleeding (64%)	E
Injection site	Injection site reaction (may be severe)	I
Metabolic / Endocrine	Hypoglycemia	E
Nervous System	Ataxia	E
Renal	Nephrotoxicity (2%) (may be severe)	D
Reproductive and breast disorders	Irregular menstruation (amenorrhea)	E
Respiratory	Adult respiratory distress syndrome (ARDS) (or other acute respiratory symptoms; especially with vincas)	E
	Pneumonitis	E D
Urinary	Bladder fibrosis (with intravesical use)	I E D
	Cystitis (25%) (with intravesical use)	I E D

* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days) E = early (days to weeks)
D = delayed (weeks to months) L = late (months to years)

Cumulative myelosuppression is a major dose-limiting adverse effect. Onset and recovery may be late (2-4 weeks and 10 weeks respectively). .

The tissue necrosis that happens with extravasation may happen days to weeks after the treatment. Patients must be observed for delayed reactions and prior injection sites carefully inspected. Soft tissue ulceration distal to the injection site following uneventful injection in a peripheral vein has been reported.

Pulmonary toxicity consisting of dyspnea, non-productive cough or pulmonary infiltrates has been reported infrequently, and may be severe, with both single agent and combination chemotherapy. Threshold dose associated with pulmonary toxicity appears to be 50-60 mg/m². Steroids may be of some benefit. Acute respiratory distress syndrome may occur with high FIO₂ concentrations and combination chemotherapy.

A syndrome of renal failure and microangiopathic hemolytic anemia (hemolytic-uremic syndrome) with hypertension, pulmonary edema and neurological symptoms has been reported in 10% of patients. This syndrome mostly appears after 6 months of therapy/ 60mg of mitomycin, and may be exacerbated with blood transfusions. Patients should be monitored for development of renal failure or hemolysis.

The incidence of cardiotoxicity may be increased in patients receiving mitomycin in combination with doxorubicin or in patients who have had prior exposure to doxorubicin. No studies report cardiotoxicity in patients only receiving mitomycin.

Genitourinary irritation, following intravesical (bladder) administration includes dysuria, cystitis, nocturia, increased micturition and hematuria. Myelosuppression has not been noted with intravesical administration. Bladder fibrosis/contraction or calcification have rarely been reported.

Mitomycin has the potential to enhance radiation injury to tissues. While often called radiation recall reactions, the timing of the radiation may be before, concurrent with or even after the administration of the mitomycin. Recurrent injury to a previously radiated site may occur weeks to months following radiation.

E - Dosing

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of white blood cell count. Dosage may be reduced and/or delayed in patients with bone marrow depression due to cytotoxic/radiation therapy. Patients should not be retreated until hematological recovery has occurred.

Adults:

Intravenous:

On days 1 and 29: 10 mg/m²
Q6-8W: 20 mg/m²
q6-8w: 2 mg/m²/day x 5 days, stop x 2 days, repeat x 1 (i.e. day 1-5 and day 8-12)

Intravesical:

q1w: 20-40 mg in SWI x 8 weeks

Dosage with Toxicity:

Dosage in myelosuppression: Modify according to protocol by which patient is being treated.

Lowest Value in Preceding Course
ANC (x10⁹/L)	Platelets (x 10⁹/L)	% Previous dose*
≥ 1	≥ 75	100
0.5 - 0.99	25-74.99	70
< 0.5	< 25	50 or discontinue

*Do not re-treat until platelets ≥ 100 x 10⁹/L, ANC ≥ 1.5 x 10⁹/L and other toxicities ≤ grade 2.

Other Toxicity:

Toxicity	Mitomycin dose
Pneumonitis	Hold and investigate if suspected. Discontinue if confirmed. Consider steroids.
Hemolytic uremic syndrome	Discontinue
Grade 3 organ/non-hematologic	Hold until ≤ grade 2 and then reduce by 25%
Grade 4 organ/non-hematologic	Discontinue

Dosage with Hepatic Impairment:

No adjustment required

Dosage with Renal Impairment:

Do not administer if creatinine > 150 µmol/L, or in patients with moderate to severe renal impairment.

Dosage in the elderly:

Has not been studied, but caution recommended due to likelihood of organ dysfunction.

Children:

Safety and efficacy have not been established.

F - Administration Guidelines

Slow push through sidearm of free flowing IV (Normal Saline)
Doses may be mixed in 50mL minibag (Normal Saline); Infuse through a free-flowing IV over 15-30 minutes

G - Special Precautions

Other:

Mitomycin is contraindicated in patients with serious infections, myelosuppression, coagulation disorder, or an increased bleeding tendency due to other causes, with known hypersensitivity or an idiosyncratic reaction to it, or any component of its formulations, even if intended for intravesical use.

High FIO₂ concentrations (anesthesia, oxygen therapy) should be avoided especially in patients with pulmonary toxicity.

Mitomycin has been shown to be carcinogenic, fetotoxic, mutagenic, clastogenic and teratogenic in animal studies and should not be used in pregnancy. Adequate contraception must be used by both sexes, during mitomycin treatment and for at least 6 months after the last dose. Breast feeding is not recommended due to the potential secretion into breast milk. Fertility may be affected.

H - Interactions

AGENT	EFFECT	MECHANISM	MANAGEMENT
vinca alkaloids (vincristine, vinblastine, vindesine)	acute bronchospasm occurring within minutes or hours after vinca alkaloid injection	Unknown	Caution

I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

Monitor Type	Monitor Frequency
CBC	Baseline and regular
Renal function tests	Baseline and periodic
Clinical exam, including pulmonary, neurological, infection, bleeding, thromboembolism, GI effects and local site toxicity	At each visit

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

Suggested Clinical Monitoring

Monitor Type	Monitor Frequency
Liver function tests	Baseline and regular
Fluid balance, in patients experiencing pulmonary toxicity

K - References

BCCA Protocol Summary for the Chemotherapy of Pseudomyxoma Peritonei using intraperitoneal Mitomycin and Fluorouracil. Accessed September 10, 2012.

McEvoy GK, editor. AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists, p. 1159-61.

Product Monograph: Mitomycin. Hospira Healthcare Corporation. June 13, 2007.

Prescribing Information: Mitozytrex® (mitomycin with glucopyranose polymers). Supergen US, November 2002.

Mitomycin: UpToDate® drug information (v19.2). Accessed September 10, 2012.

October 2017 edited indications

L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.

Info Sheet Name:

mitomycin (patient)

Info Sheet Introduction:

• For treating cancers of the stomach, colon, bladdder, as well as other types of cancer.

Info Sheet Date: Mardi, mai 22, 2018 Info Sheet body:

Medication Information Sheet

mitomycin (injection) (MY-toe-my-sin)

This document provides general information about your medication. It does not replace the advice of your health care professional. Always discuss your therapy with your health care professional and refer to the package insert for more details.

Other Name: Generic brand(s) available, Mutamycin®

Appearance:

Clear, light blue solution

What is this medication for?

For treating cancers of the stomach, colon, bladdder, as well as other types of cancer.

What should I do before I have this medication?

Tell your doctor and pharmacist if you have/had significant medical condition(s), especially if you have / had kidney problems, or any allergies.
People who have cancer or leukemia are at a higher risk of developing other cancers/leukemias (usually some years later) or blood clots. Some cancer medications may increase these risks, especially if used for a prolonged period of time. You should discuss any concerns with your doctor.

How will this medication affect sex, pregnancy and breastfeeding?

Mitomycin can harm the unborn baby and should not be used by pregnant women.
If there is ANY chance that you or your partner may become pregnant, you and your partner together must: ► Use 2 effective forms of birth control at the same time while taking this drug: Keep using birth control until 6 months after the last dose (general recommendation). Discuss with your healthcare team.
Tell your doctor right away if you or your partner becomes pregnant.
Do not breastfeed while on mitomycin treatment.

Effects on Fertility: Probable

How is this medication given?

This drug is given by injection into a vein.

What else do I need to know while on this medication?

This medication can interact with other medications and can result in the treatment not working as well or cause severe side effects.
Make sure your health care team knows about all your medications (prescription, over-the-counter, herbals and supplements). Check with your health care team before starting or stopping any of them.
For mild aches and pain or fever:
- If you feel unwell, take your temperature before taking any medications for pain or fever. They may hide a fever.
- You may take acetaminophen (Tylenol®) tablets. Ask your health care team about the right dose for you.
- Ibuprofen (Advil®, Motrin®), naproxen (Aleve®) or aspirin (acetylsalicylic acid, ASA), including low dose aspirin for heart conditions, may increase your chance of bleeding. Talk to your health care team before you start or stop these medications.
- Talk to your health care team or go to the closest emergency room right away if you have a fever. See the Fever pamphlet for more information.

What are the side effects of this medication?

The following side effects are common or severe. You may not have all of the side effects listed, while others not on this list may also occur. Discuss with your doctor if you have any unusual or bothersome symptoms.

Side effects and what to do	When to contact doctor?
More Common Side Effects

Unusual bleeding or bruising

You may have black stools, cough up blood, blood in your urine, purple or red dots on your skin or bleeding that will not stop.

Fever, chills, infection

You have a fever if your temperature taken in your mouth (oral temperature) is:

38.3°C (100.9°F) or higher at any time OR
38.0°C (100.4°F) or higher for at least one hour.

While you are getting chemotherapy treatments:

Keep a digital thermometer at home and take your temperature if you feel hot or unwell (for example, chills).
Avoid taking medications that treat a fever before you take your temperature (for example, Tylenol®, acetaminophen, Advil® or ibuprofen) as they may hide a fever.
Do not eat or drink anything hot or cold right before taking your temperature.
Wash your hands often.
Check with your doctor before getting any vaccines, surgeries or visiting your dentist.

If you have a fever, talk to your health care team or go to the closest emergency room.
See our Neutropenia (Low white blood cell count) pamphlet for more information.

Get emergency medical help right away

Mouth sores

Maintain good mouth hygiene. Regular teeth brushing with a soft toothbrush or Toothette®, and regular use of alcohol-free mouthwashes.
Instead, try a homemade mouthwash:
Mix 1 teaspoonful of baking soda and 1 teaspoonful of salt in 4 cups (1L) of water.
Avoid hot, spicy, acidic, hard or crunchy foods.
Check with your doctor or nurse as soon as you notice sores in mouth/lips or pain with swallowing. Your doctor may prescribe a prescription mouthwash to relieve mouth sores and prevent infection.
Also see Mouth Care pamphlet.*

Contact your health care team as soon as possible

Hair thinning or loss

Use a gentle soft brush; care should be taken with hair sprays, bleaches, dyes and perms.
Your hair usually grows back after your treatment ends, but the texture or colour may change.

Tiredness

Rest often; take naps if needed. Move slowly when getting up.
Eat well-balanced meals and drink plenty of fluids. Light exercise may help.
Do not drive a motor vehicle or operate machinery when feeling tired.

Contact your health care team if no improvement or if severe

Pain, burning, redness or swelling on skin where drug was injected

Let your healthcare team know right away when this happens, since this drug can harm or irritate tissues if it leaks from the vein during injection.

Nausea and vomiting (generally mild)

Drink clear fluids and avoid large meals. Get fresh air and rest.
Limit spicy, fried foods or foods with a strong smell.
Take anti-nausea drug(s) exactly as directed by your doctor. It is easier to prevent nausea than to treat it.
Contact your doctor if nausea lasts more than 48 hours or vomiting for more than 24 hours. Also see Nausea & Vomiting pamphlet.*

Contact your health care team if no improvement or if severe

Rash

Stay out of the sun; wear sunblock, a hat and cover exposed skin.
Use daily moisturizer.

Contact your health care team if no improvement or if severe

Side effects and what to do	When to contact doctor?
Less Common Side Effects, but may be Severe

Kidney problems
(lower back pain, body swelling, passing little or no urine, or recent unusual weight gain)

Get emergency medical help right away

Lung problems
(increased cough, breathing problems, chest pain, coughing blood)

Get emergency medical help right away

Heart problems
(irregular heartbeat, chest pain, fainting, swelling, shortness of breath)

Get emergency medical help right away

Sudden onset of kidney failure, bleeding, breakdown of red blood cells

Get emergency medical help right away

Blood clot (limb pain or swelling, hardened vein in limb), may occur in lungs (sudden start of coughing, breathing problems, chest pain, coughing blood)

Get emergency medical help right away

For more links on how to manage your symptoms go to www.cancercareontario.ca/symptoms.

The information set out in the medication information sheets, regimen information sheets, and symptom management information (for patients) contained in the Drug Formulary (the "Formulary") is intended to be used by health professionals and patients for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or side effects of a certain drug, nor should it be used to indicate that use of a particular drug is safe, appropriate or effective for a given condition.

A patient should always consult a healthcare provider if he/she has any questions regarding the information set out in the Formulary. The information in the Formulary is not intended to act as or replace medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

Info Sheet (English):

mitomycin patient.pdf Info Sheet (French):

mitomycine pour le patient.pdf Monograph:

mitomycin.pdf Phonetic Spelling:

MY-toe-my-sin

Cancer Type: Gastrointestinal Anus Genitourinary Bladder / Urothelial Gynecologic Vulva Type of Content: Drug Monograph Status: Null Info Sheet Status: Null Global Date: Mardi, août 9, 2016 Universal Date: 2018-05-22 00:00:00 AddThis: Title URL: mitomycin Drug Display Status: Active Revision Summary:

edited indications