Topotecan hydrochloride is available as a lyophilized powder in preservative-free, single-dose vials containing the equivalent of 4 mg of topotecan base.1730 Each vial also contains mannitol 48 mg and tartaric acid 20 mg; sodium hydroxide and hydrochloric acid may have been used to adjust the pH.1730 Reconstitute with 4 mL of sterile water for injection.1730 The reconstituted solution must be diluted for use.1730
pH
Reconstituted solution: 2.5 to 3.5.1730
Trade Name(s)
Hycamtin
Topotecan hydrochloride is administered by intravenous infusion over 30 minutes after dilution in sodium chloride 0.9% or dextrose 5%.1730 Extravasation should be avoided.1730
As with other cytotoxic drugs, applicable special handling and disposal procedures for topotecan hydrochloride should be followed.1730
Intact vials should be stored at controlled room temperature in the original carton and protected from light.1730
Topotecan hydrochloride is a light yellow to greenish powder that forms a yellow to yellow-green solution upon reconstitution.1730 Reconstituted solutions should be further diluted immediately and any unused portion discarded.1730 Diluted solutions for infusion may be stored at approximately 20 to 25°C protected from light for no more than 24 hours.1730 Diluted solutions should be discarded after 24 hours.1730
Solutions should be visually inspected for particulate matter and discoloration prior to administration.1730
Other information indicates the reconstituted drug may be stable for longer periods. Vials of reconstituted topotecan hydrochloride at a concentration of 1 mg/mL were stored at 5, 25, and 30°C both upright and inverted for 28 days. The solutions remained visually clear with no change in color, and little or no loss of topotecan hydrochloride occurred at any condition.2211
Topotecan hydrochloride 1 mg/mL reconstituted with sterile water for injection was physically and chemically stable for 28 days at 4 and 25°C protected from light. No loss of topotecan was found, and no visible precipitation or color change occurred.2243
Whether any antimicrobial effect of topotecan hydrochloride exists is uncertain but could be concentration dependent. Two studies that have been performed seem to have different results, perhaps due to the very different topotecan hydrochloride concentrations being tested.
Topotecan hydrochloride 0.01 mg/mL diluted in sodium chloride 0.9% and stored at 22°C did not exhibit an antimicrobial effect on the growth of 4 organisms (Enterococcus faecium, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans) inoculated into the solution. The author recommended that diluted solutions of topotecan hydrochloride be stored under refrigeration whenever possible and that the potential for microbiological growth be considered when assigning expiration periods.2160
Topotecan hydrochloride 1 mg/mL reconstituted with sterile water did not support the growth of 5 organisms inoculated into the solution. The USP Preservative Effectiveness Test found that Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli were not viable after 16 hours, 24 hours, and 28 days, respectively. Candida albicans and Aspergillus niger did not lose viability but did not exhibit growth during the test.2211
pH Effects
Topotecan hydrochloride has a pH near 3 maintained with tartaric acid to ensure adequate solubility of greater than 2.5 mg/mL. The solubility decreases as the pH increases, becoming virtually insoluble at pH 4.5.1747 Hydrolysis of the topotecan hydrochloride lactone ring is known to occur at pH values above 4.2140
For a list of references cited in the text of this monograph, search the monograph titled References.