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Objective: The physical compatibility of atosiban and selected drugs during simulated Y-site administration was evaluated. We also searched for any compatibility predictions regarding its physicochemical properties.Study Design: Test admixtures were prepared by mixing 5 mL of each study drug solution with 5 mL of atosiban solution in a 1:1 ratio to simulate Y-site infusion. Assessments were made immediately after mixing (baseline), and at 0.5, 1, and 3 h. Visual incompatibility was defined as a presence of haze or any visible particulate matter, gas formation, or colour change. Turbidity and pH variation of the admixtures were also assessed using instrumental methods.Results: None of the admixtures used with atosiban exhibited visual changes and no incompatibility regarding instrumental methods were observed, because no admixture had an increase of 0.5 nephelometric turbidity units, and no pH change was above one unit when compared to baseline. However, the pH of ampicillin and omeprazole admixtures fell outside of the atosiban stability range.Conclusions: Our study showed no physical incompatibility between atosiban and the test drugs in terms of visual changes or nephelometric and pH measurements. However, we recommend against atosiban and ampicillin or omeprazole coadministration until complementary compatibility studies are performed. [ABSTRACT FROM AUTHOR]

The intravenous pharmacotherapy of critically ill patients is extremely challenging due to the high number of drugs administered. We therefore evaluated the physicochemical compatibility of combinations of clonidine with drugs frequently used in an intensive care unit setting. Amiodarone, dihydralazine, furosemide, levosimendan, metamizole, milrinone, urapidil, and verapamil were each prepared as binary combinations with clonidine at the standard low and high administration concentrations. Selected ternary combinations were also analyzed. Samples were examined for physical compatibility. To verify chemical compatibility in samples deemed either physically compatible or to exhibit uncertain results, the drug content was quantified using high-performance liquid chromatography. Admixtures of clonidine with amiodarone or furosemide proved to be physically incompatible, whereas mixtures with levosimendan and metamizole exhibited results, which were not clearly meeting the specification criteria for physical compatibility. Binary combinations of clonidine with dihydralazine, milrinone, urapidil, and verapamil were found to be physically compatible. Combinations with dihydralazine, levosimendan, metamizole, milrinon, urapidil, or verapamil were chemically compatible for the analyzed concentrations. Ternary admixtures of clonidine, metamizole, and urapidil; clonidine, metamizole, and verapamil; clonidine, urapidil, and verapamil were shown to be physicochemically compatible for the analyzed concentrations. These data suggest that clonidine can be coadministered with dihydralazine, levosimendan, metamizole, milrinone, urapidil, and verapamil. However, the concomitant administration of clonidine with amiodarone or furosemide is not recommended.

The pharmacotherapy of critically ill patients is challenging due to the variety of drugs that have to be applied. As the majority of pharmaceuticals must be administered intravenously because of the critical condition of the patients, the compatibility of co-applied intravenous drugs is crucial for a safe and successful infusion therapy. Antihypertensive therapy was reported by health care professionals to be ineffective in association with concomitant application of dihydralazine and metamizole (dipyrone). As both drugs are administered in German intensive care units, we analyzed their compatibility, examined the mechanisms of underlying dihydralazine degradation, and identified reaction products of dihydralazine and metamizole. Binary combinations were prepared at the high and the low end of the nominal administration concentration. Validated high performance liquid chromatography/ultraviolet absorption (HPLC-UV) analysis was conducted to quantify drug amount and high performance liquid chromatography/mass spectrometry (HPLC-MS) was used to analyze degradation products. The combinations of dihydralazine and metamizole proved to be incompatible as dihydralazine concentration decreased immediately and considerably. Metamizole also slightly decreased over time. Specific degradation products of dihydralazine were identified and a degradation pathway was postulated. Our findings demonstrate that the intravenous co-administration of dihydralazine and metamizole should be strictly avoided due to the incompatibility of these two drugs.

Background: Published literature has demonstrated commercially available premix vancomycin (5 mg/mL) and piperacillin-tazobactam (67.5 mg/mL) as physically compatible via simulated Y-site methodology. Compatibility via actual Y-site infusion has yet to be established. Objective: To assess and compare the compatibility of commercially available premix concentrations of vancomycin and piperacillin-tazobactam via simulated and actual Y-site evaluation. Methods: Vancomycin and piperacillin-tazobactam were tested using simulated and actual Y-site infusion methodologies. Simulated Y-site compatibility was performed using previously published methods via visual inspection, turbidity evaluation, and pH evaluation. Evaluation occurred immediately, 60 minutes, 120 minutes, and 240 minutes following mixing for each mixture and control. Mixtures were considered physically incompatible if there was visual evidence of precipitation or haze, an absorbance value was greater than 0.01 A, or an absolute change of 1.0 pH unit occurred. Actual Y-site infusion was simulated to mirror antibiotic infusion in the clinical setting by nursing personnel using smart pumps and intravenous tubing. Results: No evidence of physical incompatibility was observed during simulated Y-site testing via visual inspection, turbidity assessment, and pH evaluation. Conversely, physical incompatibility was observed to the unaided eye within 2 minutes during actual Y-site infusion. Conclusions: Despite observed compatibility between vancomycin and piperacillin-tazobactam via simulated Y-site testing, visual evidence of physical incompatibility was observed during actual Y-site infusion. This poses a potential compromise to patient safety if these antibiotics are administered simultaneously in the clinical setting. Actual Y-site testing should be performed prior to clinical adoption of compatibility studies that are based solely on simulated methodologies. [ABSTRACT FROM AUTHOR]

The intravenous pharmacotherapy of critically ill patients is extremely challenging due to the high number of drugs administered. We therefore evaluated the physicochemical compatibility of combinations of clonidine with drugs frequently used in an intensive care unit setting. Amiodarone, dihydralazine, furosemide, levosimendan, metamizole, milrinone, urapidil, and verapamil were each prepared as binary combinations with clonidine at the standard low and high administration concentrations. Selected ternary combinations were also analyzed. Samples were examined for physical compatibility. To verify chemical compatibility in samples deemed either physically compatible or to exhibit uncertain results, the drug content was quantified using high-performance liquid chromatography. Admixtures of clonidine with amiodarone or furosemide proved to be physically incompatible, whereas mixtures with levosimendan and metamizole exhibited results, which were not clearly meeting the specification criteria for physical compatibility. Binary combinations of clonidine with dihydralazine, milrinone, urapidil, and verapamil were found to be physically compatible. Combinations with dihydralazine, levosimendan, metamizole, milrinon, urapidil, or verapamil were chemically compatible for the analyzed concentrations. Ternary admixtures of clonidine, metamizole, and urapidil; clonidine, metamizole, and verapamil; clonidine, urapidil, and verapamil were shown to be physicochemically compatible for the analyzed concentrations. These data suggest that clonidine can be coadministered with dihydralazine, levosimendan, metamizole, milrinone, urapidil, and verapamil. However, the concomitant administration of clonidine with amiodarone or furosemide is not recommended. [ABSTRACT FROM AUTHOR]

The intravenous pharmacotherapy of critically ill patients is extremely challenging due to the high number of drugs administered. We therefore evaluated the physicochemical compatibility of combinations of clonidine with drugs frequently used in an intensive care unit setting. Amiodarone, dihydralazine, furosemide, levosimendan, metamizole, milrinone, urapidil, and verapamil were each prepared as binary combinations with clonidine at the standard low and high administration concentrations. Selected ternary combinations were also analyzed. Samples were examined for physical compatibility. To verify chemical compatibility in samples deemed either physically compatible or to exhibit uncertain results, the drug content was quantified using high-performance liquid chromatography. Admixtures of clonidine with amiodarone or furosemide proved to be physically incompatible, whereas mixtures with levosimendan and metamizole exhibited results, which were not clearly meeting the specification criteria for physical compatibility. Binary combinations of clonidine with dihydralazine, milrinone, urapidil, and verapamil were found to be physically compatible. Combinations with dihydralazine, levosimendan, metamizole, milrinon, urapidil, or verapamil were chemically compatible for the analyzed concentrations. Ternary admixtures of clonidine, metamizole, and urapidil; clonidine, metamizole, and verapamil; clonidine, urapidil, and verapamil were shown to be physicochemically compatible for the analyzed concentrations. These data suggest that clonidine can be coadministered with dihydralazine, levosimendan, metamizole, milrinone, urapidil, and verapamil. However, the concomitant administration of clonidine with amiodarone or furosemide is not recommended.

Objectives: The main objective was to investigate Y-site compatibility of intravenous drugs with one standard total parenteral nutrition (TPN) admixture for preterm infants. Since micro-precipitation was observed in the water phase after addition of trace elements, the concentration effect on micro-precipitation formation developed as a sub-goal., Methods: Seven drugs (ampicillin, ceftazidime, fluconazole, fosphenytoin, furosemide, metronidazole and paracetamol) were mixed in three mixing ratios with one preterm TPN admixture. Samples were investigated within 1 hour and again after 4 hours. Precipitation was studied in a lipid-free version called TPN aq by light obscuration, turbidimetry and visual examination. Emulsion stability data were assessed by light obscuration and laser diffraction. pH was measured to assess the theoretical risk of precipitation and emulsion destabilisation. The influence of different concentrations of trace elements on precipitation was investigated by visual examination, turbidimetry and light obscuration., Results: Ampicillin, ceftazidime, fosphenytoin and furosemide led to precipitation after mixing with TPN aq . In some samples of TPN and fluconazole, metronidazole and paracetamol, the emulsion droplet size was above the acceptance limit, although this might also be inherent to the TPN admixture. An unexpected formation of micro-precipitate correlating with increasing amounts of added trace elements might be caused by an interaction of cysteine and copper, and complicated the compatibility assessment with drugs., Conclusions: The micro-precipitate resulting from the addition of trace elements should be investigated further. This study did not provide sufficient evidence to recommend Y-site infusion of the tested drugs and the preterm admixture; however, it might offer some additional support to other compatibility data., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)