Compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of palonosetron with cyclophosphamide and with ifosfamide during simulated Y-site administration was studied. METHODS: Test samples were prepared in triplicate by mixing 7.5 mL of palonosetron hydrochloride 50 microg (of palonosetron) per milliliter with 7.5 mL of cyclophosphamide 10 mg/mL and with ifosfamide 20 mg/mL. Physical stability was assessed by turbidimetry, particle sizing, and visual inspection. Chemical stability was assessed by stability-indicating high-performance liquid chromatography. Evaluations were performed immediately and one and four hours after mixing. RESULTS: The samples were clear and colorless when viewed in normal fluorescent room light and when viewed with a high-intensity monodirectional light. Turbidity remained unchanged, and particulate content was low and exhibited little change. Palonosetron, cyclophosphamide, and ifosfamide remained chemically stable throughout the four-hour test period. CONCLUSION: Palonosetron hydrochloride was physically compatible with cyclophosphamide or ifosfamide during simulated Y-site administration.     

Stability and compatibility of tirofiban hydrochloride during simulated Y-site administration with other drugs.

The stability and compatibility of tirofiban hydrochloride injection during simulated Y-site administration with various other drugs were studied. Tirofiban hydrochloride, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, and propranolol hydrochloride injections were each prepared from their respective concentrates in both 0.9% sodium chloride injection and 5% dextrose injection at both the minimum and maximum concentrations normally administered. The high-concentration solutions of midazolam hydrochloride and furosemide were used as is. Morphine sulfate was diluted in 5% dextrose injection only. Nitroglycerin premixed infusions, atropine sulfate injection, and diazepam injection were used as is. Tirofiban hydrochloride solutions were combined 1:1 with each of the secondary drug solutions in separate glass containers. Samples were stored for four hours at room temperature under ambient fluorescent light and were assayed for drug content and degradation by high-performance liquid chromatography and for pH, appearance, and turbidity. All mixtures except those containing diazepam remained clear and colorless, with no visual or turbidimetric indication of physical instability. Mixing of tirofiban hydrochloride and diazepam solutions resulted in immediate precipitation. all remaining mixtures remained clear. There was no significant loss of any of the drugs tested, no increase in known degradation products, and no appearance of unknown drug-related peaks. The pH of all test solutions remained constant. Tirofiban hydrochloride injection 0.05 mg/mL was stable for at least four hours when combined 1:1 in glass containers with atropine sulfate, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, morphine sulfate, nitroglycerin, and propranolol hydrochloride at the concentrations studied. Tirofiban hydrochloride was incompatible with diazepam.     

Physical compatibility of pemetrexed disodium with other drugs during simulated Y-site administration.

PURPOSE: The physical compatibility of pemetrexed disodium with selected other drugs during simulated Y-site injection was studied. METHODS: A 5 mL sample of pemetrexed disodium 20 mg/mL in 0.9% sodium chloride injection was combined with 5 mL of a solution of each of 79 other drugs. The other test drugs included antineoplastics, antiinfectives, and supportive care drugs used undiluted or diluted in 0.9% sodium chloride injection or 5% dextrose injection. Visual examinations were performed with the unaided eye in normal diffuse fluorescent light at intervals up to four hours after mixing. Combinations with no obvious incompatibility were examined further with a high-intensity monodirectional light source to enhance visualization of small particles and low-level turbidity. The combinations were also evaluated with a turbidimeter at one and four hours. All combinations without visual incompatibility were assessed with a particle sizer-counter. RESULTS: Of the 79 pemetrexed-secondary drug combinations, 55 were compatible for at least four hours. However,mixture with 24 drugs resulted in precipitation (including microprecipitation) and color change. CONCLUSION: Pemetrexed disodium was incompatible with 24 drugs during simulated Y-site administration and should not be administered with them.     

Physical and chemical compatibility of drotrecogin alfa (activated) with 34 drugs during simulated Y-site administration.

PURPOSE: The physical and chemical compatibility of drotrecogin alfa (activated) (recombinant human activated protein C) during simulated Y-site administration with drugs commonly used to treat patients with severe sepsis was determined. METHODS: Thirty-four drugs were investigated for visual compatibility with drotrecogin alfa, and included cardiovascular agents, conscious sedative agents, antibiotics, blood products, and other supportive care drugs. The physical and chemical compatibility of drotrecogin alfa with these drugs was determined using a well-established experimental model to simulate Y-site administration. Drotrecogin alfa (activated) was prepared as 100- and 1000-microg/mL solutions in 0.9% sodium chloride injection. All other drugs were prepared at maximum concentrations commonly administered in the clinical setting. Visual compatibility was assessed by visual inspection (observations of haziness, color change, or precipitate formation) and pH measurement at 0, 30, 60, and 240 minutes after mixing. RESULTS: Of the 34 test drugs, 8 were defined as visually compatible with drotrecogin alfa; these drugs were further assessed for chemical compatibility with drotrecogin alfa. The protein content, potency, and purity of drotrecogin alfa were determined at 0, 60, and 240 minutes after Y-site mixing as indicators of chemical compatibility. Six drugs (ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin) were determined to be chemically compatible with drotrecogin alfa; two drugs (cyclosporine and ticarcillin-clavulanate) were chemically incompatible with drotrecogin alfa after Y-site mixing. CONCLUSION: Ceftriaxone, cisatracurium, fluconazole, nitroglycerin, potassium chloride, and vasopressin were physically and chemically compatible with drotrecogin alfa in a simulated Y-site infusion; 28 other drugs were incompatible with drotrecogin alfa.     

Compatibility of verapamil hydrochloride with penicillin admixtures during simulated Y-site injection

The compatibility of verapamil hydrochloride during simulated Y-site injection with i.v. admixtures containing 11 different penicillins was studied. Admixtures of penicillin G potassium (62.5 mg/mL), nafcillin sodium (40 mg/mL), oxacillin sodium (40 mg/mL), ampicillin sodium (40 mg/mL), carbenicillin disodium (40 mg/mL), methicillin sodium (40 mg/mL), ticarcillin sodium (40 mg/mL), azlocillin sodium (40 mg/mL), mezlocillin sodium (40 mg/mL), piperacillin sodium (40 mg/mL), and amdinocillin (20 mg/mL) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Verapamil hydrochloride injection 4 mL (10 mg) was then added to each admixture, and the admixtures were examined macroscopically and microscopically for precipitate immediately and at 15 minutes and 24 hours after mixing. To simulate Y-site injection of verapamil, verapamil hydrochloride injection 1 mL (2.5 mg) was added to 1 mL of each penicillin admixture in a test tube. For admixtures in which precipitates formed, the pH was recorded before and after verapamil was added to the admixtures. Loss of verapamil hydrochloride when mixed with the penicillin admixtures was determined using reverse-phase high-performance liquid chromatography. Addition of verapamil hydrochloride to admixtures containing nafcillin sodium, oxacillin sodium, ampicillin sodium, and mezlocillin sodium resulted in substantial loss of verapamil hydrochloride. The results for the Y-site injection study showed visible precipitation with the same penicillin admixtures. Because a precipitate formed when verapamil hydrochloride was added to nafcillin sodium, oxacillin sodium, ampicillin sodium, or mezlocillin sodium in the diluents studied, we recommended that verapamil hydrochloride be administered separately or that the i.v. tubing be flushed thoroughly before and after this drug is administered through a Y-injection site with these penicillin admixtures.     

Compatibility of gemcitabine hydrochloride with 107 selected drugs during simulated Y-site injection.

OBJECTIVE: To evaluate the physical compatibility of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) with 107 selected drugs. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Samples of 5 mL gemcitabine (as the hydrochloride salt) 10 mg/mL in 0.9% sodium chloride injection were mixed with 5 mL samples of the selected drugs diluted in 0.9% sodium chloride injection or, if necessary to avoid incompatibilities with the diluent, 5% dextrose injection. MAIN OUTCOME MEASURES: Visual examinations of the samples were performed in normal fluorescent light with the unaided eye and using a Tyndall beam (high-intensity monodirectional light) to enhance visualization of small particles and low-level haze. The turbidity of each sample was measured as well. In selected samples, electronic particle content assessment was performed. All of the samples were assessed initially and at 1 and 4 hours. RESULTS: Most of the drugs were physically compatible with gemcitabine hydrochloride during the 4-hour observation period. However, 15 drug combinations had incompatibilities that included color change, increase in haze or turbidity, particulate formation, and gross precipitation: acyclovir sodium, amphotericin B, cefoperazone sodium, cefotaxime sodium, furosemide, ganciclovir sodium, imipenem-cilastatin sodium, irinotecan, methotrexate sodium, methylprednisolone sodium succinate, mezlocillin disodium, mitomycin, piperacillin sodium, piperacillin sodium/tazobactam sodium, and prochlorperazine edisylate. CONCLUSION: Gemcitabine hydrochloride 10 mg/mL admixed in a compatible infusion solution is physically compatible for 4 hours at room temperature with 92 of 107 tested drugs. Simultaneous Y-site administration of gemcitabine hydrochloride with the 15 drugs resulting in incompatibilities should be avoided.     

Stability and compatibility of fluorouracil and mannitol during simulated Y-site administration.

The stability and compatibility of fluorouracil admixtures with mannitol during simulated Y-site administration was studied. Fluorouracil injection 50 mg/mL was diluted with 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection to final concentrations of 1 and 2 mg/mL. Combinations of fluorouracil admixtures with 20% mannitol injection were made using equal volumes in glass test tubes; immediately after mixing and at one, two, and four hours, the samples were examined for visual incompatibilities. Duplicate combinations of fluorouracil admixtures with 20% mannitol injection were made using equal volumes in plastic syringes; immediately after mixing with internal standard in glass test tubes and at 2, 4, 8, and 24 hours, samples were removed for chemical analysis. A high-performance liquid chromatographic assay was used to determine fluorouracil concentrations. No evidence of precipitation, color change, or haze was observed. During the 24-hour study, fluorouracil concentrations remained within 6% of initial concentrations for all combinations with mannitol. Fluorouracil 1 and 2 mg/mL in 5% dextrose injection, 0.9% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection was chemically stable and visually compatible when combined with 20% mannitol injection during simulated Y-site administration.