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Compatibility of cefazolin and gentamicin in peritoneal dialysis solutions.

The compatibility of cefazolin and gentamicin in fluid commonly used for continuous ambulatory peritoneal dialysis (CAPD) was studied. Five admixtures containing cefazolin (75 mg/L and 150 mg/L) and gentamicin (8 mg/L), alone and in combination, were prepared in 1.5% dextrose peritoneal dialysis solution. Solutions were stored for 48 hours at 4 degrees C, 26 degrees C, and 37 degrees C; aliquots for drug assay were obtained at 0, 4, 8, 24, and 48 hours. HPLC and immunofluorescent assays were used to determine cefazolin and gentamicin concentrations, respectively. The cefazolin and gentamicin concentration changes over the study period did not reach statistical significance. Maximal cefazolin and gentamicin losses (12 and 7 percent of the initial concentrations, respectively) were observed at 48 hours in solutions stored at 37 degrees C. No significant differences in concentration changes were observed between combination solutions and solutions containing either cefazolin or gentamicin alone. Cefazolin and gentamicin, alone or in combination, are compatible for at least 48 hours in CAPD solutions.

Cefazolin↗

Compatibility and stability of clindamycin phosphate-aminoglycoside combinations within polypropylene syringes.

The stability and compatibility of clindamycin phosphate admixed separately with gentamicin sulfate, tobramycin sulfate, and amikacin sulfate in polypropylene syringes under specific storage conditions were studied. In duplicate syringes, clindamycin phosphate 900 mg was admixed with sterile NaCl 0.9% l ml and with either gentamicin sulfate 120 mg, tobramycin sulfate 120 mg, or amikacin sulfate 750 mg. In duplicate polypropylene syringes, control solutions of clindamycin phosphate and each aminoglycoside were prepared separately and stored under the same conditions. The clindamycin control consisted of clindamycin phosphate 900 mg in 6 ml. The gentamicin and tobramycin controls consisted of gentamicin sulfate and tobramycin sulfate 120 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. The amikacin control consisted of amikacin sulfate 750 mg in 3 ml plus 1 ml of sterile NaCl 0.9%. Drug concentrations were determined at the time of preparation and 1, 4, 8, 12, 24, and 48 hours thereafter. Aminoglycosides were assayed by fluorescence polarization immunoassay and clindamycin was assayed by high performance liquid chromatography. Visual inspections and pH determinations of each combination and control solution were performed at each assay time. For the clindamycin, gentamicin, tobramycin, and amikacin control solutions, changes in concentration were within ten percent of the original concentration. Concentrations of clindamycin and gentamicin when admixed together also remained within ten percent of the original concentration. Similar results were found with concentrations of clindamycin and amikacin when admixed together. Tobramycin and clindamycin formed a lasting precipitate upon initial contact when admixed under the study conditions.

Amikacin↗

Stability and compatibility of cimetidine hydrochloride and aminophylline in dextrose 5% in water injection.

A controlled study was conducted to assess the physical compatibility of cimetidine hydrochloride (HCl) and aminophylline and the chemical stability of an admixture of the two medications in dextrose 5% in water (D5W) injection, over 48 hours at room temperature. Three one-liter admixtures were prepared, each containing cimetidine HCl 1200 mg and aminophylline 500 mg in D5W. One liter of only cimetidine HCl 1200 mg in D5W and one liter of only aminophylline 500 mg in D5W served as controls. Samples drawn from the five admixtures and immediately frozen were analyzed for cimetidine and theophylline content at times 0, 1, 6, 24, and 48 hours using high-performance liquid chromatography. Chemical stability of each drug was assessed relative to its time-zero concentration. Samples were also drawn from each test and control solution at every time interval to assess the pH. Admixtures were stored at room temperature out of direct sunlight for the duration of the study, and were visually inspected for color change, turbidity, cloudiness, and precipitation. Recovery of cimetidine and theophylline at all test intervals, pH assessments, and visual inspections of the admixtures showed that cimetidine HCl and aminophylline are both chemically stable and physically compatible for 48 hours at room temperature in one liter of D5W.

Aminophylline↗

Compatibility and stability of cefazolin sodium, clindamycin phosphate, and gentamicin sulfate in two intravenous solutions.

We studied the compatibility and stability of clindamycin phosphate admixed with gentamicin sulfate and cefazolin sodium in small-volume diluents under specific storage conditions. In two replicate 100 ml dilutions of NaCl 0.9% injection and dextrose 5% (D5W) injection, clindamycin phosphate 900 mg was admixed with gentamicin sulfate 80 mg and cefazolin sodium 1 g. Drug concentrations were determined at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Clindamycin and cefazolin were assayed by high-performance liquid chromatography and gentamicin was assayed by fluorescence polarization immunoassay. Visual inspections and pH determinations of each solution were performed at each assay time. Test solutions were maintained at constant room temperature and fluorescent lighting. Concentrations of clindamycin and gentamicin remained greater than 90 percent of the original concentrations throughout the study. Cefazolin concentrations dropped below 90 percent in D5W injection at 4 hours after admixture and at 12 hours after admixture in NaCl 0.9% injection. Visual analyses and pH changes revealed no significant changes. The combination of clindamycin phosphate 900 mg, gentamicin sulfate 80 mg, and cefazolin sodium 1 g in D5W 100 ml was found to be compatible for up to 4 hours. The duration of compatibility for these three drugs in 100 ml of NaCl 0.9% was 12 hours.

Cefazolin↗

Stability and activity of intravenous immunoglobulin with neonatal dextrose and total parenteral nutrient solutions.

OBJECTIVE: To determine in vitro the compatibility of reconstituted intravenous immunoglobulin (IVIG) (Gammagard, Baxter-Hyland) with five different neonatal and pediatric intravenous solutions in Viaflex polyvinyl chloride bags. DESIGN: In vitro compatibility study. INTERVENTIONS: Samples were taken at time = 0, 10, 30, 60, 90, and 120 minutes and at 4, 8, 12, and 24 hours and assayed for total immunoglobulin G content and antibodies to hepatitis B surface antigen. Type III group B Streptococcus (GBS) and opsonic activity for type III GBS were analyzed at time = 0, 60, and 120 minutes and 12 and 24 hours. All results were compared with those from pure IVIG. RESULTS: Our results demonstrate that mixing IVIG with intravenous solutions commonly used in the care of premature infants (dextrose 5% in water [D5W], D15W, D5W/NaCl 0.225%, and total parenteral nutrition [TPN]) does not significantly alter total immunoglobulin G concentrations or concentration of antibodies to hepatitis B surface antigen or type III GBS. As well, the in vitro functional activity for type III GBS of the IVIG, when mixed with these solutions for up to 24 hours, remained intact. An apparent decrease in bactericidal killing was seen with the IVIG/central TPN mixture. This apparent decrease was found to be an artifact of the high concentration of glucose (20 percent) in the solution. CONCLUSIONS: We propose that Gammagard may be mixed with these solutions through Y-site connections without loss of antibody content or functional activity of the IVIG.

Antibodies, Bacterial↗

Pharmaceutical issues: preparation, administration, stability, and compatibility with other medications.

In conclusion, paclitaxel, a very active anticancer agent, is dissolved in a polyoxyethylated castor oil/alcohol vehicle, which poses some interesting challenges for drug preparation and administration. Physicians, nurses, and pharmacists should become knowledgeable about solution containers, intravenous administration sets, in-line filters, and access devices compatible with paclitaxel administration. Chemical stability studies show that paclitaxel diluted to clinically used concentrations in customary infusion fluids is stable for at least 27 hours at room temperature, which enables a 24-hour supply to be prepared in a single container. Paclitaxel has been demonstrated to be visually and turbidimetrically compatible with many other drugs during Y-site simulation studies; however, evidence of chemical compatibility for the majority of these combinations is lacking.

Diethylhexyl Phthalate↗

Compatibility of ondansetron hydrochloride with meperidine hydrochloride for combined administration.

OBJECTIVE: To determine the physical compatibility and chemical stability of ondansetron hydrochloride 0.1 and 1 mg/mL with meperidine hydrochloride 4 mg/mL admixed in NaCl 0.9% injection USP. DESIGN: Triplicate test solutions of the drugs in NaCl 0.9% injection USP were prepared and stored at 4, 22, and 32 degrees C. Samples were removed initially and at various time points over 31 days and were stored at -70 degrees C until they were analyzed. Physical compatibility was assessed by measuring solution turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer/counter, as well as by visual assessment. Chemical stability of the drugs was determined using a stability-indicating HPLC analytic method. Duplicate determinations were performed on each sample to measure the concentration of each drug. RESULTS: All admixtures were found to exhibit no visual or subvisual changes of consequence in turbidity or particle content at all observation points. Further, little or no loss of any of the drugs occurred in any concentration throughout the study. CONCLUSIONS: The physical compatibility and chemical stability of ondansetron hydrochloride with meperidine hydrochloride under the conditions of this study have been established for 7 days at 32 degrees C and 31 days at 4 and 22 degrees C.

Chromatography, High Pressure Liquid↗

Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 micrograms/mL in dextrose 5% and in sodium chloride 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at -20, 4, 23, and 32 degrees C. Samples were removed immediately and at various times over 7 days and stored at -70 degrees C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23, 32 degrees C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0-9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. CONCLUSIONS: When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 micrograms/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

Analgesics, Opioid↗

Compatibility and stability of 5-HT3 receptor antagonists: a pharmacology review.

PURPOSE/OBJECTIVES: To compare stability and compatibility among the 5-HT3 antiemetics in multidrug cytotoxic regimens. DATA SOURCES: Published articles, product-prescribing information, and direct communication with manufacturers. DATA SYNTHESIS: Stability and compatibility of ondansetron and granisetron with a variety of other agents used in the oncology setting generally are similar. Granisetron is compatible with all tested Y-site drugs; ondansetron is not compatible with amsacrine or fluorouracil. Information for dolasetron is not as readily available; therefore, comparisons are difficult to make. CONCLUSION: Although 5-HT3 receptor antagonists have made a significant impact in decreasing severe emesis, administration of complex regimens can be confusing at best for nurses because of the lack of compatibility data. By partnering with pharmacists, nurses can develop administration guidelines to minimize complications and improve outcomes. IMPLICATIONS FOR NURSING: To maximize patients' outcomes, oncology nurses must be knowledgeable about stability and compatibility of complex multidrug regimens that include the commonly used 5-HT3 receptor antagonist antiemetics.

Antiemetics↗

Compatibility and stability of the novel anti-cancer agent C1311 in infusion devices and its in vitro biocompatibility.

C1311 is the lead compound from the imidazoacridinones, a novel group of rationally designed anti-cancer agents. The compound is pharmaceutically formulated as a lyophilized product containing 100 mg C1311 (anhydrous free base) per dosage unit and requires reconstitution before intravenous administration. The aim of this study was to determine the stability of C1311 in the reconstituted solution and infusion solution and its compatibility with infusion devices. Moreover, the buffer capacity and haemolytic potential of C1311 infusion solutions, which exhibit a relatively low pH of 2-3, were evaluated in vitro. C1311 was shown to be stable in the reconstituted solution for at least 48 h and for at least 96 h after subsequent dilution in 0.9% sodium chloride and 5% dextrose. In vitro infusion simulation studies showed C1311 infusion solutions to be compatible with a low-density polyethylene administration set. Furthermore, the buffer capacity and haemolysis studies showed no indications for haemolysis or potential for vascular irritation upon continuous infusion of C1311. In conclusion, C1311 lyophilized product is adequately stable and compatible after reconstitution and in infusion fluids to be used in the clinic and is not expected to cause formulation-associated side effects in the intended administration schedule in the forthcoming Phase I clinical study.

Aminoacridines↗

Drugs and the otolaryngologist.

Numerous clinical problems arise as a result of our use of pharmaceuticals. They include untoward pharmacologic effects, socio-economic problems (excessive cost, abuse), improper administration and various medicolegal difficulties. Two areas of direct concern to the otolaryngologist are drug interactions and drug-induced diseases, problems which precipitate and prolong hospitalization and which introduce a new clinical entity, "diseases of medical progress." Otolaryngologic examples of these diseases are abundant; some are considered here in a brief explication of an area of growing concern.

Adolescent↗

Compatibility and stability of paclitaxel combined with doxorubicin hydrochloride in infusion solutions.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 300 and 1200 micrograms/mL with doxorubicin hydrochloride 200 micrograms/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 degrees C. DESIGN: The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at 4, 23, and 32 degrees C for physical and chemical stability. Physical stability was assessed by using visual observation in normal fluorescent light and a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the two drugs was evaluated by using two stability-indicating HPLC analytic techniques. RESULTS: All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred within 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained at more than 97% in all samples throughout the study. Doxorubicin hydrochloride also was stable throughout the study period, remaining above 90% in all samples at all storage temperatures. CONCLUSIONS: Admixtures of paclitaxel 300 and 1200 micrograms/mL with doxorubicin hydrochloride are limited in their utility time by paclitaxel microcrystalline precipitation. All combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 degrees C.

Antineoplastic Combined Chemotherapy Protocols↗

Physical and chemical stability of palonosetron HCl in 4 infusion solutions.

BACKGROUND: Palonosetron HCl is a selective 5-HT(3) receptor antagonist used for the prevention of chemotherapy-induced nausea and vomiting. Palonosetron HCl may be diluted in an infusion solution for administraton. Consequently, stability information is needed for palonosetron HCl admixed in common infusion solutions. OBJECTIVE: To evaluate the physical and chemical stability of palonosetron HCl in concentrations of 5 and 30 microg/mL in dextrose 5% injection, NaCl 0.9% injection, dextrose 5% in NaCl 0.45% injection, and dextrose 5% in lactated Ringer's injection. METHODS: Triplicate test samples of palonosetron HCl at each concentration in each diluent were tested. Samples were stored and evaluated at appropriate intervals for up to 48 hours at room temperature ( approximately 23 degrees C) and 14 days under refrigeration (4 degrees C). Physical stability was assessed using turbidimetric and particulate measurement, as well as visual inspection. Chemical stability was assessed by HPLC. RESULTS: All of the admixtures were initially clear and colorless when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low initially and remained low throughout the study. The drug concentration was unchanged in any of the samples at either temperature throughout the study. CONCLUSIONS: Palonosetron HCl is physically and chemically stable in all 4 common infusion solutions for at least 48 hours at room temperature and 14 days under refrigeration.

Antiemetics↗