Medication Safety in Intravenous Therapy: A Compatibility Study of Clonidine with Drugs Frequently Used in Intensive Care

Abstract

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 Physicochemical Compatibility of Sildenafil Injection with Parenteral Medications Used in Neonatal Intensive Care Settings

“…The ratio of the mean peak areas was determined and the 95% CI of the ratio was calculated using the confidence limits from a two-sided t -test (α = 0.05; SigmaPlot V.15; Inpixon GmbH, Düsseldorf, Germany). Consistent with previous studies, incompatibilities of sildenafil:drug combinations were defined as a ratio of the mean peak area outside the range of 90–110% [ 8 , 9 , 18 , 19 , 20 ].…”

Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy

“…Traditionally, the chemical stability of drugs for infusion, in our case after co-administration via the same port, has been studied using quantitative methods like high-performance liquid chromatography, − while physical compatibility (e.g., precipitation, color change, and oil droplet growth in an emulsion) frequently was relying on visual observations, aided by microscopy or Tyndall beam. − These approaches have methodological and practical shortcomings not least when combinations of three or more drugs are of interest. Developing validated methods for multiple component solutions demands time and resources, and relying on visual control for detection of precipitates does not cover sub-visible particles neither does it provide the solid form identity of the precipitate.…”

“…Traditionally, the chemical stability of drugs for infusion, in our case after co-administration via the same port, has been studied using quantitative methods like high-performance liquid chromatography, 9 − 13 while physical compatibility (e.g., precipitation, color change, and oil droplet growth in an emulsion) frequently was relying on visual observations, aided by microscopy or Tyndall beam. 14 − 16 These approaches have methodological and practical shortcomings not least when combinations of three or more drugs are of interest.…”

Physicochemical compatibility of pentoxifylline injection with high‐concentration parenteral medications

“…Turbidity and pH measurements are commonly conducted in physical compatibility studies and have been reported in physicochemical compatibility investigations. 7 , 8 , 9 , 10 , 11 However, there are resource implications for these tests, not least the requirement for large sample volumes (typically > 10 ml), which is problematic for expensive drugs. Furthermore, the intrinsic value of some physical compatibility tests is unclear and interpretation or specification limits may be inconsistent 12 ; for example, in regard to pH unit shift.…”

“…Furthermore, the intrinsic value of some physical compatibility tests is unclear and interpretation or specification limits may be inconsistent 12 ; for example, in regard to pH unit shift. 9 , 10 , 11 In regard to quantifying only the PTX concentration, we have assumed that physicochemical incompatibility would be the result of interaction between the two drugs and should be detected by the HPLC assay of the primary drug. Although there may be value in quantifying the secondary drug if chemical incompatibility is detected or suspected, a significant impediment to quantifying all of the secondary drugs would be developing and validating HPLC assays for the full range of drugs.…”