.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.

d be fully reevaluated after each course of mitomycin, and the dose reduced if the patient has experienced any toxicities. doses greater than 20 mg/m 2 have not been shown to be more effective, and are more toxic than lower doses. the following schedule is suggested as a guide to dosage adjustment: nadir after prior dose leukocytes/mm 3 platelets/mm 3 percentage of prior dose to be given >4000 >100,000 100% 3000–3999 75,000–99,999 100% 2000–2999 25,000–74,999 70% <2000 <25,000 50% no repeat dosage should be given until leukocyte count has returned to 4000/mm 3 and a platelet count to 100,000/mm 3 . when mitomycin 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, the drug should be stopped since chances of response are minimal. stability unreconstituted mitomycin stored at room temperature is stable for the lot life indicated on the package. avoid excessive heat (over 40°c, 104°f). reconstituted with sterile water for injection to a concentration of 0.5 mg per ml, mitomycin is stable for 14 days refrigerated or 7 days at room temperature. diluted in various i.v. fluids at room temperature, to a concentration of 20 to 40 micrograms per ml: i.v. fluid stability 0.9% sodium chloride injection 12 hours sodium lactate injection 24 hours the combination of mitomycin (5 mg to 15 mg) and heparin (1,000 units to 10,000 units) in 30 ml of 0.9% sodium chloride injection is stable for 48 hours at room temperature. procedures for proper handling and disposal of anticancer drugs should be considered. several guidelines on this subject have been published. 1-8 there is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

ood 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 of the cases. elderly patients may be more susceptible than younger patients to injection site reactions (see precautions: geriatric use ). renal toxicity 2% of 1,281 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 and may be life-threatening. dyspnea with a nonproductive cough and radiographic evidence of pulmonary infiltrates may be indicative of mitomycin-induced pulmonary toxicity. if other etiologies 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 chemotherapy and maintained at flo 2 concentrations greater than 50% perioperatively. hemolytic uremic syndrome (hus) this serious complication of chemotherapy, consisting primarily of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm 3 ), and irreversible renal failure (serum creatinine ≥1.6 mg/dl) has been reported in patients receiving systemic mitomycin. microangiopathic hemolysis with fragmented red blood cells 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. a high mortality rate (52%) has been associated with this syndrome. 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. the incidence of the syndrome has not been defined. therapy for the syndrome is investigational. cardiac toxicity congestive heart failure, often treated effectively with diuretics and cardiac glycosides, has rarely been reported. 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 1,281 patients. other headache, blurring of vision, confusion, drowsiness, syncope, fatigue, edema, thrombophlebitis, hematemesis, diarrhea, 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. malaise and asthenia have been reported as part of postmarketing surveillance. bladder fibrosis/contraction has been reported with intravesical administration (see precautions ).

vely low doses, the percent of a dose excreted in urine increases with increasing dose. in children, excretion of intravenously administered mitomycin is similar. animal toxicology 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 tumor incidence in male sprague-dawley rats, and a greater than 50 percent increase in tumor incidence in female swiss mice.