Get your patient on Mitomycin - Mitomycin injection, Powder, Lyophilized, For Solution (Mitomycin)

• 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:

• 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.

This was the most common and most serious toxicity, occurring in 605 of 937 patients (64.4%). Thrombocytopenia and/or leukopenia may occur anytime within 8 weeks after onset of therapy with an average time of 4 weeks. Recovery after cessation of therapy was within 10 weeks. About 25% of the leukopenic or thrombocytopenic episodes did not recover. Mitomycin produces cumulative myelosuppression.

This has occurred in approximately 4% of patients treated with mitomycin. Cellulitis at the injection site has been reported and is occasionally severe. Stomatitis and alopecia also occur frequently. Rashes are rarely reported. The most important dermatological problem with this drug, however, is the necrosis and consequent sloughing of tissue which results if the drug is extravasated during injection. Extravasation may occur with or without an accompanying stinging or burning sensation and even if there is adequate blood 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 )

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.

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. Steriods 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 FIO ₂ concentrations greater than 50% perioperatively.

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.

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.

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 post marketing surveillance. Bladder fibrosis/contraction has been reported with intravesical administration (see PRECAUTIONS ).

To report SUSPECTED ADVERSE REACTIONS, contact RK Pharma Inc at 1-844-757-4276 (1-844-RKPHARM) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.