Mitomycin

A to Z Drug Facts

Actions An antibiotic that inhibits the synthesis of DNA. Serum half-life after a 30 mg bolus injection is 17 min. Primarily hepatic metabolism. Clearance rate is inversely proportional to maximal serum concentration because of saturation of degradative pathways. The percent excreted in urine increases with increasing dose.

 Indications Palliative treatment of disseminated adenocarcinoma of stomach or pancreas.

Bladder, colorectal, or breast cancer; squamous cell carcinoma of head and neck, lungs, or cervix; pterygium.

 Contraindications Primary therapy as a single agent; to replace surgery or radiotherapy; hypersensitivity or idiosyncratic reaction to mitomycin; thrombocytopenia; coagulation disorder; increase in bleeding tendency caused by other causes.

 Route/Dosage

Mitomycin 0.02% Eye Drops for Pterygium

ADULTS: Reconstitute 5 mg vial of mitomycin with 10 mL sterile water for injection for a concentration of 0.5 mg/mL. Transfer 6 mL (3 mg) to a sterile 15 mL eye dropper bottle. Add 9 mL of sterile water for injection for a final concentration of 0.2 mg/mL (0.02% solution). This solution is stable for 1 wk at room temperature and 2 wk refrigerated.

Mitomycin 0.2 mg/mL Ophthalmic Solution for Intraoperative Use

ADULTS: Reconstitute 5 mg vial of mitomycin with 10 mL sterile water for injection. Transfer the contents of the vial to a 30 mL sterile vial. Add 15 mL of sterile water for injection for a final volume of 25 mL (0.2 mg/mL). This solution is stable for 52 wk frozen, 2 wk under refrigeration, and 24 hr at room temperature.

Palliative Treatment of Disseminated Adenocarcinoma of Stomach or Pancreas

Adult and Pediatric: Initial dose: 10 to 20 mg/m², q 6 to 8 wk. Fully reevaluate patients after each course of therapy. Do not exceed 20 mg/m². Give an additional course of therapy only after the leukocyte and platelet counts have recovered. Subsequent doses of mitomycin may be adjusted according to the following schedule.

For dosage adjustments of mitomycin, nadir after prior dose (cells/mm³): 100% of prior dose to be given to more than 3000 leukocytes and more than 75,000 platelets; 70% of prior dose to be given to 2000 to 2999 leukocytes and 25,000 to 74,999 platelets; 50% of prior dose to be given to less than 2000 leukocytes and less than 25,000 platelets.

If disease progression continues after 2 courses, discontinue therapy.

Interactions Use of vinca alkaloids in patients who have previously or simultaneously received mitomycin has resulted in acute shortness of breath and severe bronchospasm.

Lab Test Interferences None well documented.

 Adverse Reactions

DERMATOLOGIC: Alopecia; desquamation; pruritus. GI: Moderate to low potential for nausea and vomiting; anorexia; mucositis; hepatic artery thrombosis (intra-arterial administration only). GU: Amenorrhea. HEMATOLOGIC: Bone marrow suppression; thrombocytopenia nadir at 4 to 6 wk; leukopenia nadir at 6 wk (can be delayed 8 wk or less). RENAL: Increased serum creatinine and BUN; glomerular sclerosis; hemolytic uremic syndrome may result in irreversible renal failure. RESPIRATORY: Interstitial pneumonitis; pulmonary fibrosis. OTHER: Hemolytic uremic syndrome: Usually occurs after 6 mo of therapy. Course may be chronic or fulminant. Plasmapheresis may be indicated for treatment. Fever.

 Precautions

Pregnancy: Safety for use during pregnancy has not been established. Teratological changes have been noted in animal studies. Bone marrow suppression: Thrombocytopenia and leukopenia may occur any time within 8 wk (average, 4 wk) of therapy; recovery after therapy is within 10 wk. They may contribute to overwhelming infection in an already compromised patient. Hemolytic uremic syndrome: Hemolytic uremic syndrome, a serious syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure has occurred. Dosage adjustment for renal insufficiency: Do not give to patients with a serum creatinine more than 1.7 mg/dL. Mitomycin Dosage Adjustment Based on Renal Function Ccr: Percent of Usual Dose > 60 mL/min 100: 30 to 60 mL/min 75 10 to 29 mL/min 75: < 10 mL/min 50 Extravasation risk: Local irritation or phlebitis may occur. Refer to your institution specific protocol. Adult respiratory distress syndrome: Exercise caution to use only enough oxygen to provide adequate arterial saturation since oxygen itself is toxic to the lungs. Pay careful attention to fluid balance; avoid overhydration.

 Administration/Storage

• Protect powder for injection from light and store at room temperature.
• Dilute with sterile water for injection. Shake the vial; allow to stand at room temperature for complete dissolution. Maximum concentration is 0.5 mg/mL; more concentrated solutions crystallize easily.
• Reconstituted mitomycin contains no preservative and should be used within 24 hr.
• Diluted in various IV fluids at room temperature to a concentration of 20 to 40 mcg/mL, stability is as follows: 5% Dextrose Injection, 3 hr; 0.9% NaCl Injection, 12 hr; Sodium Lactate Injection, 24 hr.
• The combination of mitomycin (5 to 15 mg) and heparin (1000 to 10,000 units) in 30 mL of 0.9% NaCl Injection is stable for 48 hr at room temperature.
• Administer IV, intra-arterial, or intravesical.
• Administer by IV push injection or IV side arm into a running infusion.

 Assessment/Interventions

• Monitor for evidence of renal or pulmonary toxicity.
• Perform hematologic studies (eg, platelet count, WBC, differential, hemoglobin) during therapy and for at least 8 wk following discontinuation of the drug.
• Avoid use in patients with thrombocytopenia, coagulation disorders, or an increased bleeding tendency, and patients with a serum creatinine more than 1.7 mg/dL.
• Advise patients of potential bone marrow suppression.
• Monitor patients receiving at least 60 mg for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Advise patient, family, or caregiver that medication will be used in combination with other agents to achieve maximum benefit possible.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; hives; shortness of breath or difficulty breathing; fever, chills or other signs of infection; sores in mouth; unusual bleeding or bruising; pain, redness or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea or appetite loss; persistent or worsening general body weakness.
• Instruct patient to not take any prescription or otc medications or dietary supplements unless advised to do so by health care provider.
• Caution women of childbearing potential to avoid becoming pregnant during therapy.
• Instruct women of childbearing potential to notify health care provider if they become pregnant, plan on becoming pregnant, or are breastfeeding.
• Advise patient, family or caregiver that following discharge frequent follow-up visits and laboratory tests will be required to monitor therapy and to be sure to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts