Mitomycin

Pronunciation: MY-toe-MY-sin
Class: Antibiotic

Trade Names

Mutamycin
- Powder for injection 5 mg
- Powder for injection 20 mg
- Powder for injection 40 mg

Pharmacology

An antibiotic that inhibits the synthesis of DNA.

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Pharmacokinetics

Absorption

Mitomycin is rapidly cleared from the serum. C max is 2.4 mcg/mL (after 30 mg IV injection), 1.7 mcg/mL (after 20 mg IV), and 0.5 mcg/mL (after 10 mg IV).

Metabolism

Metabolism is primarily hepatic and has saturable metabolic pathways.

Elimination

Approximately 10% is excreted in urine (increases as dose increases) and Cl is affected primarily by hepatic metabolism. Serum t ½ is 17 min after 30 mg bolus.

Special Populations

Renal Function Impairment

Observe patients for evidence of renal toxicity. Do not give to patients with a serum creatinine more than 1.7 mg/dL.

Indications and Usage

Palliative treatment of disseminated adenocarcinoma of stomach or pancreas.

Unlabeled Uses

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.

Dosage and Administration

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 (59° to 86°F) 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 h at room temperature (59° to 86°F).

Palliative Treatment of Disseminated Adenocarcinoma of Stomach or Pancreas
Adults and Children Initial dose

10 to 20 mg/m 2 , every 6 to 8 wk. Fully reevaluate patients after each course of therapy. Do not exceed 20 mg/m 2 . 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/mm 3 )

100% of prior dose to be given to more than 3,000 leukocytes and more than 75,000 platelets; 70% of prior dose to be given to 2,000 to 2,999 leukocytes and 25,000 to 74,999 platelets; 50% of prior dose to be given to less than 2,000 leukocytes and less than 25,000 platelets.

If disease progression continues after 2 courses, discontinue therapy.

General Advice

  • 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 h.
  • 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 h; 0.9% NaCl Injection, 12 h; Sodium Lactate Injection, 24 h.
  • The combination of mitomycin (5 to 15 mg) and heparin (1,000 to 10,000 units) in 30 mL of 0.9% NaCl Injection is stable for 48 h at room temperature.
  • Administer IV, intra-arterial, or intravesical.
  • Administer by IV push injection or IV side arm into a running infusion.

Storage/Stability

Protect powder for injection from light and store at room temperature (59° to 86°F).

Drug Interactions

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

Laboratory Test Interactions

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).

Genitourinary

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.

Miscellaneous

Hemolytic uremic syndrome

Usually occurs after 6 mo of therapy. Course may be chronic or fulminant. Plasmapheresis may be indicated for treatment. Fever.

Precautions

Warnings

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 has been reported and may occur with monotherapy or combination therapy. Usually occurs with doses of at least 60 mg. Blood product transfusion may exacerbate symptoms.


Pregnancy

Safety for use during pregnancy has not been established. Teratological changes have been noted in animal studies.

Renal Function

Dosage adjustment for renal function impairment

Do not give to patients with a serum creatinine more than 1.7 mg/dL.

Mitomycin Dosage Adjustment Based on Renal Function CrCl Percent of Usual Dose > 60 mL/min 100 30 to 60 mL/min 75 10 to 29 mL/min 75 < 10 mL/min 50

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.

Extravasation risk

Local irritation or phlebitis may occur. Refer to your institution specific protocol.

Patient Information

  • 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 max benefit.
  • 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.
  • Caution women of childbearing potential to avoid becoming pregnant during therapy.

Copyright © 2009 Wolters Kluwer Health.

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