The physical and chemical compatibility of topotecan 56 microg/mL (as the hydrochloride) with 18 other drugs during simulated Y-site injection was studied. A vial of topotecan hydrochloride was reconstituted under aseptic conditions with sterile water for injection to yield a solution containing 1 mg of topotecan base per milliliter and further mixed with 0.9% sodium chloride injection or 5% dextrose injection. Equal volumes of topotecan solution and each secondary drug, also prepared in 0.9% sodium chloride injection or 5% dextrose injection, were mixed in sterile vials. All mixtures were stored at 20-23 degrees C under normal fluorescent light. Samples were taken initially and at four hours for analysis by high-performance liquid chromatography, visual inspection, and pH measurement. With a few exceptions, the drug combinations exhibited no visible change in color or clarity initially or after four hours, and the concentration of topotecan hydrochloride and of the secondary drugs was 95% or more of the initial concentration. The concentration of topotecan hydrochloride dropped to 88.7% of the initial concentration after four hours when the drug was mixed with ticarcillin disodium and with clavulanate potassium in 5% dextrose injection. An intense yellow color and a slight haze developed immediately after topotecan hydrochloride was mixed with dexamethasone sodium phosphate or with fluorouracil in 0.9% sodium chloride injection. The topotecan-mitomycin combination in both diluents became pale purple immediately and turned dark pink-lavender within four hours, after which analysis showed 15-20% degradation of mitomycin. During simulated Y-site injection, topotecan hydrochloride was physically and chemically compatible with 15 of 18 drug products.