Physically Compatible Research Articles

Evaluation of the Physical Compatibility of Intravenous Methocarbamol in Lactated Ringer’s, 0.45% Normal Saline, and Plasma-Lyte A

Background: The need to determine physical compatibility of intravenous admixtures is directly related to patient safety and patient outcomes. While the provision of multi-modal analgesic strategies has increased over the past decade, a paucity of data exists regarding physical compatibility of select medications. Objectives: To evaluate the physical compatibility of methocarbamol in Lactated Ringer’s (LR), 0.45% normal saline (0.45% NaCl), and Plasma-Lyte A (PLA) at concentrations of 4, 10, and 20 mg/mL. Methods: Admixtures were prepared and evaluated using previously validated methods under a laminar flow hood using aseptic technique. Samples were prepared in a triplicate manner, 3 mL aliquots were placed into polymethyl methacrylate cuvettes for evaluation at time points 0, 1, 5, 8, and 24 hours. Visual inspection of samples included assignment of a number: 0—no precipitation, 1—trace evidence of precipitation, 2—slight haze, 3—medium haze, and 4—heavy precipitation. Any evidence of precipitation was considered significant. A variable wavelength spectrophotometer set at 547 nanometers was used to measure absorbance. A change in absorbance of ±0.010 was considered significant. A change in pH of ±0.1 was considered significant. Results: No significant changes occurred relating to visual inspection or absorbance across all concentrations and time points for LR; however, there was a significant change in pH across all concentrations at hour 5. In 0.45% NaCl and PLA, no remarkable changes occurred across all concentrations and time points regarding visual observation, spectrophotometric absorbance, and pH analysis. Conclusions: Methocarbamol at concentrations of 4, 10, and 20 mg/mL is physically compatible for up to 1 hour in LR. Methocarbamol is physically compatible in 0.45% NaCl and PLA for up to 24 hours. Chemical stability tests are warranted to confirm these findings.

Physical compatibility of ceftriaxone and cefepime in 0.45% sodium chloride, Ringer’s lactate solution, and Plasma-Lyte A

ObjectivesThe compatibility of intravenous fluids with medications is of paramount concern to pharmacists and is an imperative component of ensuring patient safety. Data regarding the physical compatibility of medications with...

Stability and Compatibility of an Intramuscular Fetal Anesthetic Cocktail for Fetal Intervention

Introduction: The aim of the study was to evaluate chemical stability and physical compatibility when combining fentanyl, rocuronium, and atropine in a fixed ratio to support intramuscular drug delivery during fetal intervention and surgery. Methods: A highly concentrated combination of fentanyl, rocuronium, and atropine was created based on common prescribing practices at a maternal-fetal care center. Chemical stability testing was completed using liquid chromatograph mass spectrometry-mass spectrometry (LC/MS-MS) to detect and quantitate atropine, rocuronium, and fentanyl, with fentanyl-d5 being an internal standard at 6, 12, 24, and 36 h following sample preparation. Physical compatibility testing was completed using United States Pharmacopeia (USP) <788> recommended analytical technique of light obscuration in addition to novel backgrounded membrane imaging at 6 and 24 h following sample preparation. Physical compatibility was determined using USP <788> particle count limits for both techniques. Results: Based on LC/MS-MS results, the samples retained expected medication concentrations at all time points tested. For physical compatibility testing, the particle counts met criteria to be considered compatible per USP <788> large-volume particle count thresholds at 6 h by both methods but exceeded tolerable thresholds at 24 h. Discussion/Conclusion: The combination of rocuronium, fentanyl, and atropine for intramuscular fetal administration is physically compatible and chemically stable for 6 h.

Harmonising IV Oxycodone with Paediatric Perioperative Medications: A Compatibility Study Through Y-Type Connectors.

Co-administering multiple intravenous (IV) agents via Y-connectors is a common practice in hospitalised and fasting surgical patients. However, there is a lack of reliable data confirming the physical compatibility of some combinations including IV oxycodone, a drug that is gaining increasing popularity in the perioperative period. Concern regarding physical drug incompatibilities precludes concurrent coadministration with other common drugs through a single lumen. This can result in the cessation of infusions to allow the administration of other medications, resulting in exacerbation of acute pain. This study aims to evaluate the physical compatibility of IV oxycodone with some commonly co-administered drugs and IV fluids. Mixtures of oxycodone (1mg.mL-1) and the tested drugs and IV fluids were prepared in a ratio of 1:1. The mixtures were examined at 0 and 60 minutes from mixing and assessed using the European Conference Consensus Standards. This involved visual inspection (precipitation, turbidity, colour change, gas formation), spectrophotometry, and pH change. The tested drugs included ketamine, tramadol, clonidine, vancomycin, piperacillin/tazobactam, dexmedetomidine, cefotaxime, gentamicin, and paracetamol. In addition, the commonly used IV fluids tested included glucose 5% + sodium chloride 0.9% + 60 mmol potassium chloride, plasmalyte + dextrose 5%;plasmalyte + dextrose 5% + 55 mmol potassium chloride, plasmalyte + dextrose 5% + 55mmol potassium acetate, plasmalyte + dextrose 5% + 55mmol potassium dihydrogen phosphate, Hartmann's solution, Standard pediatric Total Parenteral Nutrition (TPN) 20/100 and TPN 25/150. IV oxycodone (1 mg.mL-1) showed no visual changes; no spectrophotometric absorption variability at 350, 410, or 550nm; and no pH changes of >0.5 at 0 or 60 minutes with any of the tested drugs or fluids in the concentrations tested. According to European Consensus Conference Standards, IV Oxycodone at 1 mg.mL-1 is physically compatible in a ratio of 1:1 v/v with all investigated drugs and fluids tested for at least 60 minutes.

Physical compatibility of colistin with analgesics during simulated Y-site administration.

Special consideration is needed when intravenous drugs are administered simultaneously using a Y-site connector. This study aimed to investigate the physical compatibility of colistin with 6 analgesics at concentrations commonly used in clinical practice. A pharmaceutical preparation of colistin was dissolved according to the manufacturer's instructions and diluted to a concentration of 1.5 mg/mL or 0.67 mg/mL (of colistin base). Simulated administration via Y-site infusion set was performed by mixing 5 mL of colistin solution with an equal volume of a solution of one of 6 intravenous analgesics. Infusion solutions of ibuprofen, ketoprofen, metamizole sodium, morphine sulfate, paracetamol, and tramadol hydrochloride were studied. For each analgesic tested, concentrates for injection were diluted with 2 solvents, resulting in 11 different combinations with each concentration of the colistin solution. The mixtures were visually inspected, and their turbidity was measured directly after mixing and at 3 consecutive time points (30, 60, and 120 minutes). Additionally, the pH of the mixtures was measured after 120 minutes and compared with the pH of the analgesic and the colistin solutions. During visual inspection with the unaided eye, no precipitate formation or gas evolution was observed in any of the tested analgesics except for sodium metamizole, where the yellow color of the solutions was observed. For samples containing the mixture of ibuprofen and colistin, the turbidity measurements revealed the presence of turbidity in the studied mixtures. The greatest change in pH relative to the value immediately after preparation was noted for combinations of ketoprofen and morphine sulfate with the tested antibiotic. Colistin was found to be incompatible with ibuprofen and metamizole sodium formulations. It should also not be combined with morphine sulfate due to the significant differences in the pH value of the preparations. The colistin 0.67 mg/mL and 1.5 mg/mL infusion solutions were physically compatible with ketoprofen, tramadol hydrochloride, and paracetamol.

In vitro compatibility study of a new preservative‐free multidose 0.6% bilastine eye drop formulation containing sodium hyaluronate with soft and gas rigid permeable contact lenses

Aims/Purpose: Despite many patients with allergic conjunctivitis are contact lens wearers, research on the physical compatibility of antihistamine eye drops and contact lenses is lacking. The aim of this work was to evaluate the in vitro compatibility of a new preservative‐free bilastine eye drops with the main types of contact lenses.Methods: The physical compatibility of a new preservative‐free bilastine eye drops in comparison with an isotonic saline solution, was evaluated in three types of contact lenses: hydrogel, silicone hydrogel and gas rigid permeable. Physical properties evaluated: diameter of the lens, posterior vertex power, radius of curvature, physical appearance, and spectral transmittance were characterized. For initial characterization, the lenses (n = 60) were equilibrated in a saline solution at 20–25°C for 24 h. After, 10 lenses of each type were separately immersed in either the saline solution or the bilastine formulation, both at 20–25°C, for 1 h, and then subjected to 30 wash cycles. The physical characterization was carried out after 1, 15 and 30 wash cycles, measurements performed in triplicate. Measurement methods and tolerance limits of the physical properties and general procedure and performance criteria for assessing the physical compatibility of contact lens were conducted in accordance with the guidelines (UNE‐EN ISO 18369‐3:2007; UNE‐EN ISO 18369‐2:2007; UNE‐EN ISO 11981:2013).Results: The incubation of contact lenses with the new preservative‐free bilastine eye drop formulation did not affect any of the physical properties of the lenses and the results were comparable to those exposed to the control saline solution. The physical properties of all the contact lenses tested in both conditions complied with the manufacturer's specifications and tolerance limits stablished.Conclusion: These results indicate that the new preservative‐free bilastine eye drop is physically compatible with soft and rigid gas permeable contact lens.

Physical compatibility of sulbactam/durlobactam with select intravenous drugs during simulated Y-site administration.

Sulbactam/durlobactam is a combination antibiotic designed to target Acinetobacter baumannii, including carbapenem-resistant and multidrug-resistant strains. The objective of this study was to determine the physical compatibility of sulbactam/durlobactam solution during simulated Y-site administration with 95 intravenous (IV) drugs. Vials of sulbactam/durlobactam solution were diluted in 0.9% sodium chloride injection to a volume of 100 mL (the final concentration of both drugs was 15 mg/mL). All other IV drugs were reconstituted according to the manufacturer's recommendations and diluted with 0.9% sodium chloride injection to the upper range of concentrations used clinically or tested undiluted as intended for administration. Y-site conditions were simulated by mixing 5 mL of sulbactam/durlobactam with 5 mL of the tested drug solutions in a 1:1 ratio. Solutions were inspected for physical characteristics (clarity, color, and Tyndall effect), turbidity, and pH changes before admixture, immediately post admixture, and over 4 hours. Incompatibility was defined as any observed precipitation, significant color change, positive Tyndall test, or turbidity change of ≥0.5 nephelometric turbidity unit during the observation period. Sulbactam/durlobactam was physically compatible with 38 out of 42 antimicrobials tested (90.5%) and compatible overall with 86 of 95 drugs tested (90.5%). Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, ciprofloxacin, daptomycin, levofloxacin, phenytoin sodium, vecuronium, and propofol. The Y-site compatibility of sulbactam/durlobactam with 95 IV drugs was described. These compatibility data will assist pharmacists and nurses to safely coordinate administration of IV medications with sulbactam/durlobactam.

Y-site simulation compatibility study of 10% calcium salts with various injectable solutions during toxicological resuscitation

PurposeTo determine the physical compatibility of 10% calcium chloride and 10% calcium gluconate in combination with injectable solutions, administered in the paediatric and adult intensive care unit setting during toxicological...

The Physical Compatibility of Glycopyrrolate and Rocuronium.

Scientific evidence has rarely, if at all, been reported in the literature demonstrating analytical confirmation of the physical compatibility and stability of glycopyrrolate and rocuronium combined. The purpose of this experiment was to determine if glycopyrrolate and rocuronium are physically compatible. Glycopyrrolate and rocuronium were combined in various containers, observed over a 60-minute period, and compared against positive and negative controls. Measured metrics included color change, precipitate formation, Tyndall beam test, turbidity, and pH. Statistical analyses were used to assess significance of data trends. The combination of glycopyrrolate and rocuronium did not result in any color change, precipitate formation, a positive Tyndall beam test, or a significantly positive turbidity and did not result in any significant change in pH, regardless of container. Per the protocol used in this study, glycopyrrolate and rocuronium were determined to be physically compatible.

Assessment of compatibility of rhIGF-1/rhIGFBP-3 with neonatal intravenous medications

BackgroundRecombinant human (rh)IGF-1/IGFBP-3 protein complex, administered as a continuous intravenous infusion in preterm infants, is being studied for the prevention of complications of prematurity.MethodsWe conducted in vitro studies to evaluate the physical and chemical compatibility of rhIGF-1/IGFBP-3 with medications routinely administered to preterm neonates. In vitro mixing of rhIGF-1/IGFBP-3 drug product with small-molecule test medications plus corresponding controls was performed. Physical compatibility was defined as no color change, precipitation, turbidity, gas evolution, no clinically relevant change in pH/osmolality or loss in medication content. Chemical compatibility of small molecules was assessed using liquid chromatography (e.g., reverse-phase HPLC and ion chromatography), with incompatibility defined as loss of concentration of ≥ 10%. A risk evaluation was conducted for each medication based on in vitro compatibility data and potential for chemical modification.ResultsIn vitro physical compatibility was established for 11/19 medications: caffeine citrate, fentanyl, fluconazole, gentamicin, insulin, intravenous fat emulsion, midazolam, morphine sulfate, custom-mixed parenteral nutrition solution (with/without electrolytes), parenteral nutrition solution + intravenous fat emulsion, and vancomycin (dosed from a 5 mg/mL solution), but not for 8/19 medications: amikacin, ampicillin, dopamine, dobutamine, furosemide, meropenem, norepinephrine, and penicillin G, largely owing to changes in pH after mixing. Small-molecule compatibility was unaffected post-mixing, with no loss of small-molecule content. For physically compatible medications, risk analyses confirmed low probability and severity of a risk event.ConclusionCo-administration of rhIGF-1/rhIGFBP-3 drug product with various medications was assessed by in vitro studies using case-by-case risk analyses to determine the suitability of the products for co-administration.

Physical compatibility of remimazolam with opioid analgesics, sedatives, and muscle relaxants during simulated Y-site administration.

There is a lack of information on the compatibility of remimazolam with opioid analgesics, muscle relaxants, and other sedatives. This study aimed to evaluate the physical compatibility of remimazolam with these drug classes. Remimazolam was combined with 1 or 2 target drugs (remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam). Ten physical compatibility tests were conducted, including four 3-drug compatibility tests. Remimazolam was dissolved in 0.9% sodium chloride injection to a final concentration of 5 mg/mL. Other medications were diluted in 0.9% sodium chloride injection to obtain clinically relevant concentrations. Compatibility tests were conducted with 3 test solutions, wherein remimazolam and the target drugs were compounded at equal volume ratios (1:1 or 1:1:1). Visual appearance was assessed and testing of Tyndall effect, turbidity, and pH was performed immediately after mixing and then again 1 hour and 4 hours after mixing. Appearance and turbidity were evaluated by comparison with the control solution of each target drug diluted with 0.9% sodium chloride injection to the same concentration as the test solution. All drugs tested were determined to be compatible with remimazolam. The drug combination with the highest change of turbidity was remimazolam and vecuronium (a mean increase of 0.16 NTU relative to the remimazolam control solution), 4 hours after mixing. The combination with the highest pH was remimazolam, fentanyl, and vecuronium (mean [SD], 3.76 [0.01]), 4 hours after mixing. The combination of remimazolam and fentanyl showed a larger change in pH at 4 hours after mixing (a mean increase of 2.6%) than immediately after mixing. Remifentanil, fentanyl, rocuronium, vecuronium, dexmedetomidine, and midazolam are physically compatible with remimazolam during simulated Y-site administration.

Compatibility and Physical Properties of Dexamethasone-Ondansetron Intravenous Admixture.

Purpose: This work aimed at evaluating the impact of different concentrations and final volumes on the compatibility and physical properties of dexamethasone-ondansetron intravenous (IV) admixture. Methods: The IV admixture of dexamethasone-ondansetron was prepared at different concentrations using normal saline solution as solvent. The final volume of the IV admixture was prepared at 50 and 100 ml. Turbidity was measured as an indicator of physical compatibility of the IV admixture of dexamethasone-ondansetron using UV-visible spectrophotometer and the pH of the IV admixture was measured on day 0, 7,14, and, 21 as an index of chemical stability. Also, the particle size and potential molecular interactions of the admixtures were determined using particle size analyzer and Fourier Transform infrared spectrometry analysis, respectively. Additionally, the effect of preservatives on the IV admixture was also evaluated. Results: Precipitation was observed for mixtures with amounts of dexamethasone and ondansetron exceeding 8 and 16 mg, respectively, in a final volume of 50 ml. For all mixtures with final volume of 100 ml, clear solutions void of any precipitates were observed. The pH of the solution had no effect on the precipitation of the dexamethasone-ondansetron during storage up to 21 days. Analyses of the precipitate formed revealed the presence of molecular interactions between dexamethasone and ondansetron. The benzyl alcohol used as a preservative affected the compatibility of the IV admixture compatibility. Conclusion: Thus, for the preparation of clear, physically compatible normal saline solutions of dexamethasone-ondansetron IV admixture, the maximum amounts of the respective drugs should not exceed 8 and 16 mg in total volume of 50 ml or 20 and 16 mg in a final volume of 100 ml.

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

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.

Physical Compatibility and Chemical Stability of Fentanyl and Naloxone Hydrochloride in 0.9% Sodium Chloride Injection Solution for Patient-Controlled Analgesia Administration.

Background and ObjectiveThe combination of naloxone hydrochloride (NH) and fentanyl citrate (FC) in patient-controlled analgesia (PCA) is examined to reduce the risk of opioid-induced nausea and vomiting. However, there are no such commercially available drug mixtures, and there is also no published evidence on the compatibility and stability of NH and FC. Thus, the primary purpose of the current research is to investigate the physical compatibility and chemical stability of NH when mixed with FC over a 72-h period in a 0.9% sodium chloride injection solution for PCA administration under storage at 4°C and 25°C.MethodsTest solutions of 20 μg/mL FC and 4 μg/mL NH were prepared and stored in polyvinyl chloride (PVC) bags or glass bottles with a 0.9% sodium chloride injection solution as the diluent. During the 72-h storage period at 4°C or 25°C without light protection, the concentrations of the test drugs were assayed via high-performance liquid chromatography (HPLC), and the physical compatibility was determined with the naked eye. Furthermore, pH measurement of each sample was also performed with a pH meter.ResultsThe percentages of the initial concentrations of FC and NH in the various solutions were maintained at a minimum of 98% over the 72-h study period. All of the mixtures remained clear and colourless throughout the observation period, and no precipitation or turbidity was observed in any of the batches.ConclusionThe 20 μg/mL FC test solution was physically compatible and chemically stable with the 4 μg/mL NH test solution when stored at 4°C or 25°C in PVC bags or glass bottles containing the 0.9% sodium chloride injection solution.

The Physical Compatibility of Clinically Used Concentrations of Diltiazem Hydrochloride With Heparin Sodium.

Background: Acute treatment of atrial fibrillation often requires concomitant intravenous (IV) continuous infusions of unfractionated heparin and diltiazem. Concomitantly infusing these medications through the same IV line minimizes multiple IV sites. Diltiazem and heparin visual compatibility have been previously investigated but with limited drug dwell times and differing drug concentrations leading to inconsistent published results. Objective: To investigate the physical compatibility of diltiazem hydrochloride at concentrations of 5 and 1 mg/mL combined with an equal volume of heparin sodium 100 units/mL. Methods: Using a 0.22-µm filter, 15 mL of heparin sodium were placed into a polyvinyl chloride infusion bag followed by 15 mL of either diltiazem hydrochloride 5 or 1 mg/mL. Admixtures were prepared in triplicate. Each admixture was investigated for visual precipitation, spectrophotometric absorbance, and pH change at baseline and 1, 5, 8, and 24 hours after mixing. Physical incompatibility was determined by visual observation, increased spectrophotometric absorbance, and demonstrative pH changes. Results: Each diltiazem 5 mg/mL admixture exhibited a slight haze and enhanced absorbance readings indicating turbidity while none revealed a demonstrative pH change. None of the diltiazem 1 mg/mL assessments revealed visual precipitation or suggested turbidity. Only one pH reading at 5 hours revealed a demonstrative change from baseline. Conclusions: Our findings indicate that infusing diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL in the same IV line cannot be advocated. In contrast, our findings suggest that heparin sodium 100 units/mL infused with diltiazem hydrochloride 1 mg/mL is physically compatible but chemical stability was not assessed.

Physical compatibility of insecticides and fungicides and their phytotoxicity on castor

All 18 combinations of insecticides and fungicides tested were physically compatible. The combinations viz.,novaluron + carbendazim, acetamiprid + carbendazim, acetamiprid + carbendazim 12% + mancozeb 63% andbuprofezin + carbendazim 12% + mancozeb 63% showed phytotoxic symptoms like vein clearing and scorching onleaves, remaining all other treatment combinations were compatible.

Compatibility of acetaminophen with central nervous system medications during simulated Y-site injection.

The critical care patient commonly receives alot of medications including acetaminophen and central nervous system (CNS) agents. However, research on compatibility between acetaminophen and CNS medication is still limited. Physical compatibility was evaluated using Y-site simulation by mixing one CNS medication with 10 mg mL-1 of acetaminophen solution under aseptic conditions with a1 : 1 ratio. The Y-site simulation mixture was subsequently kept in aclean glass tube for incompatibility investigation during 24 hours. The aliquot solutions were visually inspected with bare eyes then additionally with aTyndall light beam, microscope, and pH at 0, 1, 4, and 24 hours. Medications were considered compatible if there was no visual change (color/gas or turbidity), and no significant particles or precipitates, which referred to United States Pharmacopeia 788 (USP 788), and pH changes less than 0.5 units. During 24 hours, intravenous acetaminophen was physically compatible with haloperidol, ketamine, midazolam, pethidine, rocuronium and tramadol. Meanwhile, phenytoin, and propofol showed incompatibility with acetaminophen right away. Within four hours, five medications (dexketoprofen, fentanyl, ketorolac, diazepam and phenobarbital) showed incompatibility. Two medications (atropine sulfate and metamizole) were also found to be incompatible with acetaminophen under observation for 24 hours. Nine of 15 common CNS medications in critical care tested with acetaminophen were physically incompatible for 24 hours.

Y-Site Compatibility of Intravenous Levetiracetam With Commonly Used Critical Care Medications.

Purpose: Levetiracetam is an antiepileptic medication commonly used in critical care areas for seizure treatment or prophylaxis. Compatibility data of levetiracetam with other critical care medications are limited, which can make administration challenging. This study aims to assess the physical Y-site compatibility of intravenous levetiracetam with some other commonly used critical care medications. Methods: Y-site administration was simulated by independently mixing levetiracetam with each of 11 selected medications in a 4-dram, colorless, screw-cap, glass vial, at a 1:1 ratio. Clinically used concentrations of each medication were compounded in 0.9% sodium chloride following United States Pharmacopeia chapter 797 standards. Physical compatibility was observed and assessed at 0, 15, and 30 minutes after mixing. Medication mixtures were considered physically incompatible if there was visual evidence of color change, gas evolution, haze, or particulate formation, pH change >10%, or if they had an absorbance value >0.010 A. Results: No evidence of physical incompatibility was observed during simulated Y-site testing with cisatracurium 1 mg/mL, dexmedetomidine 4 µg/mL, fosphenytoin 15 mg PE/mL, norepinephrine 16 mg/mL, norepinephrine 32 mg/mL, norepinephrine 64 mg/mL, piperacillin-tazobactam 33.75 mg/mL, propofol 10 mg/mL, vancomycin 5 mg/mL, or vasopressin 1 unit/mL when tested in 0.9% sodium chloride. Levetiracetam was incompatible with piperacillin-tazobactam 45 mg/mL. Conclusion: Levetiracetam 5 mg/mL in 0.9% sodium chloride was found to be physically compatible for 30 minutes with 10 of the 11 medications tested during simulated Y-site administration.

Assessment of the Physical Compatibility of Eravacycline and Common Parenteral Drugs During Simulated Y-site Administration

PurposeEravacycline is a broad-spectrum, intravenous fluorocycline antibiotic approved for the treatment of complicated intra-abdominal infections in adults. A 60-minute infusion is recommended for each infused dose. Compatibility data that may allow convenient Y-site administration of eravacycline with other parenteral medications are unavailable. We aimed to determine the physical compatibility of eravacycline with other intravenous medications by simulated Y-site administration. MethodsEravacycline was reconstituted according to published prescribing information and diluted with 0.9% sodium chloride to a concentration of 0.6 mg/mL. Simulated Y-site administration was performed by mixing 5 mL of eravacycline with an equal volume of 51 other intravenous medications, including crystalloid and carbohydrate hydration fluids and 20 antimicrobials. Secondary medications were assessed at the upper range of concentrations considered standard for intravenous infusion. Mixtures underwent visual inspection and turbidity measurement immediately on mixture and at 3 subsequent time points (30, 60, and 120 minutes after admixture), and pH was measured at 60 minutes for comparison with the baseline value of the secondary medication. FindingsEravacycline was physically compatible with 41 parenteral drugs (80%) by simulated Y-site administration. Incompatibility was observed with albumin, amiodarone hydrochloride, ceftaroline fosamil, colistimethate sodium, furosemide, meropenem, meropenem/vaborbactam, micafungin sodium, propofol, and sodium bicarbonate. ImplicationsEravacycline for injection was physically compatible with most parenteral medications assessed. Pharmacists and nurses should be knowledgeable of the observed incompatibilities with eravacycline to prevent the unintentional mixing of incompatible intravenous medications.

Investigations of Physical Compatibilities of Commonly Used Intravenous Medications with and without Parenteral Nutrition in Pediatric Cardiovascular Intensive Care Unit Patients.

Many pediatric intensive care patients require numerous specialized intravenous (IV) medications at various dosages in multiple fluids often with nutritional support. This requires several venous access points due to lack of Y-site compatibility data for combinations of two or more drugs. This project investigated physical compatibilities of intravenous medications: alprostadil, calcium gluconate, dexmedetomidine, epinephrine, norepinephrine, esmolol, furosemide, vasopressin, and milrinone with and without lipid-free total parenteral nutrition (TPN) commonly used in a pediatric cardiovascular intensive care unit (CVICU) patient. Actual drug combinations were evaluated using a simulated Y-site study design. Compatibility was determined based on observational data: odor (change/appearance), evolution of gas, and visual appearance combined with physical or chemical endpoints with predefined acceptance criteria: change in pH (± 1 unit), and turbidity (>0.5 NTU) at eight time points between 0 and 240 min. All binary drug combinations along with the four drug plus TPN combination were found to be physically compatible up to 240 min. The three drug combinations were determined to be incompatible and were not evaluated with TPN. This study demonstrates the utility of simulated Y-site study design to multi-drug combinations and increases the scientific body of knowledge related to medications used in a pediatric CVICU.