Mutamycin

This drug may cause a certain serious, sometimes fatal side effect (hemolytic uremic syndrome). This condition may result in anemia, low platelet counts, and kidney disease. Blood transfusions may make the symptoms worse. Tell your doctor immediately if you notice symptoms such as pink/bloody urine or change in amount of urine.

MUTAMYCIN® (mitomycin for injection, USP) (also known as mitomycin and/or mitomycin-C) is an antibiotic isolated from the broth of Streptomyces caespitosus which has been shown to have antitumor activity. The compound is heat stable, has a high melting point, and is freely soluble in organic solvents.

Action

MUTAMYCIN (mitomycin) selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of MUTAMYCIN (mitomycin) -induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed.

In humans, MUTAMYCIN (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 I.V., the maximal serum concentrations were 2.4 µg/mL, 1.7 µg/mL, and 0.52 µg/mL, respectively. Clearance is effected primarily by metabolism in the liver, but metabolism occurs in other tissues 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 MUTAMYCIN (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 MUTAMYCIN (mitomycin) is similar.

Animal Toxicology

MUTAMYCIN (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% increase in tumor incidence in male Sprague-Dawley rats, and a greater than 50% increase in tumor incidence in female Swiss mice.

Mitomycin should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.

Serious side effects have been reported with the use of mitomycin including: allergic reactions (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; or fever, chills, or signs of infection); kidney damage (little or no urine production, blood in the urine, lower back or side pain, difficulty urinating, or swelling of the ankles or feet); lung and heart problems; and others. Talk to your doctor about the possible side effects from treatment with mitomycin.

Tell your doctor or nurse right away if you notice redness, pain or swelling at the place of injection or anywhere else on your skin.

• Cancer
• Cancer Fatigue

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.100 d

• Administer mitomycin only after complete hematologic recovery from any previous chemotherapy occurs.100

Administration

Administer IV.100 c d

Has been administered intravesically†; notan approved route of administration.100 115 120 121 130 131 138 d

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer via a functioning IV catheter;100 c d some clinicians recommend administering the drug through tubing of an IV infusion.c Use care to avoid extravasation.100 d (See Mucocutaneous Effects under Cautions.)

Reconstitute vial containing 5, 20, or 40 mg of mitomycin with 10, 40, or 80 mL of sterile water for injection, respectively, to provide a solution containing approximately 0.5 mg/mL.100 c d

Shake vial to dissolve.100 c d If the powder does not dissolve immediately, allow the vial to stand at room temperature until complete dissolution occurs.100 c d

Dosage

Consult published protocols for dosages of mitomycin and other chemotherapeutic agents and the method and sequence of administration.c

Individualize dosage based on clinical and hematologic response and tolerance of the patient and whether or not other myelosuppressive therapy also is being used.100 c d

Reevaluate patients after each course of therapy and adjust dosages as needed.100 d

Adults

Initially, 20 mg/m2 as a single IV dose every 6–8 weeks.100 d Doses >20 mg/m2 are not more effective and increase risk of toxicity.100 d

Adjust subsequent dosages according to the hematologic response to the previous dose.100 d (See Table 1.)Do not administer repeat dosage until leukocyte count has returned to 4000/mm3 and platelet count to 100,000/mm3.100 d

If disease continues to progress after 2 courses of therapy, discontinue the drug since likelihood of response is minimal.100 d

Usual dosage: 20–60 mg once weekly,115 116 118 120 125 126 127 128 administered as soon as possible following transurethral resection (TUR).117 128 For patients treated within 6–24 hours following TUR, a 6-month course of therapy generally is sufficient; however, for patients in whom intravesical therapy is instituted ≥24 hours following surgery, a 12-month course usually is recommended.117 128 No additional benefit demonstrated for continued maintenance therapy.115 116 120 124 128 131

Special Populations

Hepatic Impairment

No special dosage recommendations at this time.100 d

Renal Impairment

Do not administer if Scr >1.7 mg/dL.100 d (See Renal Effects under Cautions.)

Geriatric Patients

No special dosage recommendations at this time.100 d

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

While you are being treated with mitomycin, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. Mitomycin may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Mitomycin can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

If mitomycin accidentally seeps out of the vein into which it is injected, it may damage the skin and cause scarring. In some patients, this may occur weeks or even months after this medicine is given. Tell the doctor or nurse right away if you notice redness, pain, or swelling at the place of injection or anywhere else on your skin.

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. Therefore, the following studies should be obtained repeatedly during therapy and for at least eight weeks following therapy: platelet count, white blood cell count, differential, and hemoglobin. The occurrence of a platelet count below 100,000/mm 3 or a WBC below 4,000/mm 3 or a progressive decline in either is an indication to withhold further therapy until blood counts have recovered above these levels.

Patients should be advised of the potential toxicity of this drug, particularly bone marrow suppression. Deaths have been reported due to septicemia as a result of leukopenia due to the drug.

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.

Usage in Pregnancy

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.

1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice Pittsburgh, PA: Oncology Nursing Society; 1999:32-41.
2. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, National Institutes of Health; 1983. US Dept of Health and Human Services, Public Health Service publication NIH 83-2621.
3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1591.
4. National Study Commission on Cytotoxic Exposure. – Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia. 1983;1:426-428.
6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin. 1983;33:258-263.
7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.
8. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.). Am J Health SystPharm. 1996;53:1669-1685.

Manufactured for :

Accord BioPharma Inc.

1009 Slater Road, Suite 210-B,

Durham, NC 27703. USA

Manufactured by :

Intas Pharmaceuticals Limited,

Ahmedabad – 380 009, India.

10 0823 0 668295

Issued - September, 2016

Carton Label-Mutamycin ® (Mitomycin) for injection USP 40 mg/vial

NDC 69448- 003-38

Mutamycin ®
(Mitomycin) For Injection USP
40 mg

Rx only

WARNING:
MUST BE ADMINISTERED IV TO AVOID
TISSUE DAMAGE

Carton Label-Mutamycin ® (Mitomycin) for injection USP 20 mg/vial

NDC 69448- 002-11

Mutamycin ®
(Mitomycin) For Injection USP
20 mg

Rx only

WARNING:
MUST BE ADMINISTERED IV TO AVOID
TISSUE DAMAGE

Carton Label-Mutamycin ® (Mitomycin) for injection USP 5 mg/vial

NDC 69448- 001-05

Mutamycin ®
(Mitomycin) For Injection USP
5 mg

Rx only

WARNING:
MUST BE ADMINISTERED IV TO AVOID
TISSUE DAMAGE

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Mutamycin (mitoMYcin (systemic)), please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Review Date: March 7, 2018