Mitomycin is available as a lyophilized powder in amber vials containing 5, 20, or 40 mg of mitomycin with mannitol 10, 40, or 80 mg, respectively.1725 Reconstitute the 5-, 20-, or 40-mg vials with 10, 40, or 80 mL, respectively, of sterile water for injection and shake to aid dissolution.1725 Allow to stand at room temperature if dissolution does not take place immediately.1725 The reconstituted solution contains 0.5 mg/mL of mitomycin.1725
pH
Reconstituted solutions have a pH between 6 and 8.1725
Trade Name(s)
Mutamycin
Mitomycin is administered intravenously through a functioning intravenous catheter.1725 Extravasation should be avoided because cellulitis, ulceration, and sloughing may occur.1725
In the event of spills or leaks, Bristol-Myers Squibb has recommended the use of sodium hypochlorite 5% (household bleach) or potassium permanganate 1% to inactivate mitomycin.1200
Intact vials should be stored at controlled room temperature and protected from light.1725 Avoid excessive heat.1725 Reconstituted solutions should be protected from light and are stable for 14 days stored under refrigeration or for one week at room temperature.1725
Mitomycin (Kyowa) 0.6 and 0.8 mg/mL in water for injection exhibited 10% loss in seven days at 21°C in the dark. When stored at 4°C in the dark, the 0.6-mg/mL concentration lost 7% in seven days. Although exhibiting no loss in 24 hours when stored at 4°C in the dark, the 0.8-mg/mL concentration developed a fine, pink, needle-like precipitate in three days. At a higher concentration of 1 mg/mL in water for injection similar results were obtained. Refrigeration resulted in fine, pink, needle-like precipitate formation in 24 hours. The 1-mg/mL concentration stored at 21°C exposed to fluorescent light exhibited 6% loss in 24 hours and developed the fine, pink, needle-like precipitate in four days. Stored at a higher temperature of 25°C in the dark, losses of 6% in 24 hours and 10% in seven days were found with no precipitate forming.1503
pH Effects
Mitomycin is very stable in solution at a neutral pH but undergoes more rapid decomposition at acidic and basic pH.1119; 1203; 1204; 1866 The decomposition is complex and pH dependent, producing different decomposition products in acidic and basic solutions.1119; 1283; 1284 The pH of maximum stability is approximately pH 7.1072; 1203; 1204; 1379 At pH 7, a 10% mitomycin loss occurs in seven days at room temperature.1072 At a concentration of 0.05 mg/mL in dextrose 5% buffered to pH 7.8 with a mixture of phosphates, mitomycin was stable for 15 days at room temperature and over 120 days when refrigerated.1118
Both pH and storage temperature are important to mitomycin stability. Mitomycin (150 to 600 mcg/mL) stability was tested in pH 6, 7, and 8 buffer solutions. The drug was less stable at pH 6 than at pH 7 and especially pH 8. At pH 6, drug losses of around 96 and 41% occurred at room temperature and under refrigeration, respectively, over 28 days. However, mitomycin was more stable at pH 7 and 8. Drug losses when stored under refrigeration for 28 days were about 10 to 20% in this pH range.2651
Temperature Effects
Heating mitomycin 0.6 mg/mL in sodium chloride 0.9% to 100°C resulted in a 24% drug loss in 30 minutes and a 58% loss in one hour.1285
Freezing Solutions
Mitomycin 0.6 mg/mL in sodium chloride 0.9% crystallized out of solution when frozen at -20°C. The particles did not redissolve after thawing in a microwave oven. Freezing to -30°C, below the eutectic temperature, resulted in no loss of mitomycin during four weeks of storage, microwave thawing, and refreezing at -30°C for another four weeks.1285
Light Effects
The stability of mitomycin is not adversely affected by the presence or absence of normal fluorescent light.1503
Syringes
Mitomycin (Bristol-Myers Squibb) reconstituted to a concentration of 0.5 mg/mL with sterile water was repackaged in 1-mL polypropylene tuberculin syringes (Sherwood). Syringes were stored at both 5 and 25°C protected from light. About 7% mitomycin loss occurred in 11 days at 25°C and about 8% loss in 42 days at 5°C.2179
Filtration
Mitomycin 10 to 75 mcg/mL exhibited little or no loss due to sorption to either cellulose nitrate/cellulose acetate ester (Millex OR) or Teflon (Millex FG) filters.1415; 1416
For a list of references cited in the text of this monograph, search the monograph titled References.