No effects of nirmatrelvir/ritonavir on darunavir plasma trough concentrations: a case report.

COVID-19 may be associated with worst outcomes in people living with HIV compared with HIV-negative patients. Nirmatrelvir/ritonavir can be safely co-administered with all the HIV antiretroviral drugs, without considering dose adjustment. However, no studies have formally investigated the effect of a double booster (ritonavir plus cobicistat) regimen on darunavir concentrations. We presented a case describing the lack of effects of adding nirmatrelvir/ritonavir on darunavir plasma trough concentrations in a patient with HIV already on treatment with a booster-based antiretroviral regimen. We believe this could be a reassuring message for physicians, allowing them to prevent unnecessary denial of COVID-19 treatment or inappropriate discontinuation of co-medications in patients with HIV.

Combination of a propofol emulsion with alpha-2 adrenergic receptor agonists used for multimodal analgesia or sedation in intensive care units: a physicochemical stability study.

OBJECTIVES: To assess the physicochemical stability of the combination of a propofol emulsion with an alpha-2 (α2) adrenergic receptor agonist (α2A; clonidine or dexmedetomidine) under conditions mimicking routine practice in an intensive care unit or in multimodal analgesia procedures. METHODS: We developed and validated three stability-indicating methods based on high-performance liquid chromatography with ultraviolet (HPLC-UV) detection. Eight different conditions per combination were evaluated in triplicate, with variations in the simulated, bodyweight-adjusted dose level and the drugs' flow rate. The drugs were mixed in clinically relevant concentrations and proportions and then stored unprotected from light, in clear glass vials at room temperature for 96 hours. At each sampling point, we assessed the chemical stability (the HPLC-UV drug level, pH, and osmolality) and physical compatibility (visual aspect, zeta potential (ZP), mean droplet diameter (MDD, Z-average) and polydispersity index (PDI)). We validated our stability findings in positive and negative control experiments. RESULTS: Over the 96-hour test, the concentrations of propofol, clonidine and dexmedetomidine did not fall below 90% of the initial value, and the pH and osmolality were stable. The visual aspect of the mixed propofol emulsions did not change. The MDD remained below 500 nm (range 165-195 nm). The PDI was always below 0.4; 78.7% of the measurements were below 0.1 and 21.3% were between 0.1 and 0.4. The ZP measurements (-31.3 to -42.9 mV) suggested that the emulsion was stable. The MDD and PDI increased slightly at 96 hours under some conditions, which might indicate early destabilisation of the emulsion. Given that the MDD remained below 500 nm, these emulsions are compatible with intravenous administration. CONCLUSIONS: Our results demonstrate the chemical and physical compatibility of propofol-α2 agonist mixtures at concentrations and in proportions representative of standard protocols when stored unprotected from light at room temperature for 96 hours.

Physical compatibility of lipid emulsions and intravenous medications used in neonatal intensive care settings.

OBJECTIVE: The purpose of this study was to investigate the physical compatibility of intravenous lipid emulsions with parenteral medications used in neonatal intensive care. METHODS: Lipid emulsion and drug solutions were combined 1:1 in glass vials, inspected for physical incompatibility at 0, 1 and 2 hours, and assessed on the basis of lipid droplet size at 0 and 2 hours after mixing. Intravenous fluid controls (Water for Injection, sodium chloride 0.9% w/v, glucose 5% w/v), positive controls (gentamicin, albumin), negative controls (metronidazole, paracetamol, vancomycin) and 21 previously untested drug combinations were evaluated. RESULTS: No phase separation, change in colour, gas production or other visible anomaly was observed. The between-run mean droplet diameter (MDD) for SMOFlipid20% alone (0.301±0.008 µm) was comparable to the lipid emulsion/intravenous fluid and lipid emulsion/drug solution combinations. In addition to gentamicin and albumin, caffeine citrate (20 mg/mL) was shown to be incompatible with the lipid emulsion. All other lipid:drug combinations were compatible, based on the MDD data. CONCLUSION: Intravenous lipid emulsions were found to be compatible with 20 parenteral medications, including antimicrobial agents, inotropes, anti-inflammatory drugs and caffeine base, in simulated Y-site conditions. The lipid emulsion was incompatible with caffeine citrate injection.

Evaluation of Strategies for Reducing Vancomycin-Piperacillin/Tazobactam Incompatibility.

BACKGROUND: Drug incompatibility is defined as a physical-chemical reaction between two or more injectable drugs and that results mainly in precipitation or insolubility. Several strategies for reducing incompatibilities have been implemented empirically in intensive care units. However, these strategies have never been compared directly (and particularly in terms of the particulate load and drug mass flow rate) under standardized conditions. The objective of the present in vitro study was to evaluate the impact of various strategies for preventing incompatibility between simultaneously infused vancomycin and piperacillin/tazobactam. METHODS: An in-line filter, a dilute vancomycin solution (5 mg/mL), and an alternative saline administration line were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. The antibiotic concentration was measured in an HPLC-UV assay. RESULT: The use of an in-line filter and an alternative saline administration route did not significantly reduce the particulate load caused by vancomycin-piperacillin/tazobactam incompatibility. Dilution of the vancomycin solution was associated with a significantly lower particulate load and maintenance of the vancomycin mass flow rate. DISCUSSION: It is important to systematically compare the efficacy of strategies for preventing drug incompatibility. The use of diluted vancomycin solution gave the best results in the case of vancomycin-piperacillin/tazobactam incompatibility.

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

PURPOSE: To 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 resuscitation involving calcium channel blockers and beta-blockers. METHODS: Forty-eight combinations were prepared at room temperature, including the following products: calcium chloride, calcium gluconate, insulin, epinephrine, norepinephrine, highly concentrated dextrose solution, sodium chloride, Plasma-Lyte A and Ringer's lactate. A visual evaluation at times 0, 1, 4, 24, 48 and 72 hours and a particle count test with the LS-20 particle counter at times 0, 4, 24 and 72 hours were performed. The admixtures were considered incompatible if there was a precipitate, a colour change, turbidity, viscosity or a gas formation. The stability of calcium salts was also tested in empty IV bags and syringes by the particle count test. RESULTS: All drug mixtures were found to be compatible by visual evaluation and using the particle counter based on United States Pharmacopoeia chapter 788 (USP<788>) specifications. Calcium salts were compatible with insulin and vasopressors in the tested combinations. The stability of 10% calcium salts in empty IV bags and polypropylene syringes was demonstrated for up to 48 hours at room temperature. CONCLUSION: All the combinations tested were physically compatible for up to 72 hours at room temperature. Clinical use of calcium salt infusions, at an undiluted concentration, in combination with these injectable solutions in a toxicological resuscitation context is considered clinically acceptable.

Avoiding incompatible drug pairs in central-venous catheters of patients receiving critical care: an algorithm-based analysis and a staff survey.

PURPOSE: In a critical care setting, we aimed to identify and solve physico-chemical drug incompatibilities in central-venous catheters considering the staffs' knowledge and assumptions about incompatibilities. METHODS: (i) After positive ethical vote, an algorithm to identify incompatibilities was developed and applied. The algorithm was based on KIK® database and Stabilis® database, the drug label, and Trissel textbook. (ii) A questionnaire was created and used that asked staff for knowledge and assumptions about incompatibilities. (iii) A 4-step avoidance recommendation was developed and applied. RESULTS: (i) At least one incompatibility was identified in 64 (61.4%) of 104 enrolled patients. Eighty one (62.3%) of 130 incompatible combinations affected piperacillin/tazobactam and in 18 (13.8%) each furosemide and pantoprazole. (ii) 37.8% (n = 14) of the staff members participated in the questionnaire survey (median age: 31, IQR: 4.75 years). The combination of piperacillin/tazobactam and pantoprazole was incorrectly judged to be compatible by 85.7%. Only rarely felt the majority of respondents unsafe in administering drugs (median score: 1; 0, never to 5, always). (iii) In those 64 patients with at least one incompatibility, 68 avoidance recommendations were given, and all were fully accepted. In 44 (64.7%) of 68 recommendations "Step 1: Administer sequentially" was suggested as a avoidance strategy. In 9/68 (13.2%) "Step 2: Use another lumen", in 7/68 (10.3%) "Step 3: Take a break", and in 8/68 (11.8%) "Step 4: Use catheters with more lumens" were recommended. CONCLUSIONS: Although incompatibilities were common, the staff rarely felt unsafe when administering drugs. Knowledge deficits correlated well with the incompatibilities identified. All recommendations were fully accepted.

A new function in the Stabilis database: physical compatibility and incompatibility of injectable drugs to secure Y-site administration.

OBJECTIVES: In intensive care units, the mixing of injectable drugs via Y-site administration is often necessary. However, some mixtures can lead to physical incompatibility or chemical instability. To assist healthcare professionals, several databases such as Stabilis compile compatibility and stability data. The objectives of this study were to update the online database Stabilis by adding physical compatibility data to the website and to characterise the incompatibility data already present in the database by specifying the phenomenon at the origin of the incompatibility and its time of occurrence. METHODS: Bibliographic sources referenced in Stabilis were evaluated using several criteria. After the evaluation, studies were rejected or the data they contain were added to the database. Data entries contained the following information: name of the two injectable drugs involved in the mixture and their concentration if available, the dilution solvent and the phenomenon at the origin of the incompatibility and its time of occurrence for incompatibility data. Three functions of the website were modified, including the 'Y-site compatibility table' function, which allows creation of customised compatibility tables. RESULTS: A total of 1184 bibliographic sources were evaluated, 77.3% (n=915) of which were scientific articles, 20.5% (n=243) were Summaries of Product Characteristics and 2.2% (n=26) were communications in a pharmaceutical congress. After evaluation, 28.9% (n=342) of the sources were rejected. From the 71.1% (n=842) sources selected, 8073 (70.2%) compatibility data entries and 3433 incompatibility data entries (29.8%) were made. With the addition of these data, the database contained compatibility and incompatibility data for 431 injectable drugs. CONCLUSIONS: Since the update, the 'Y-site compatibility table' function has seen its traffic increased by about 66% (∼1500 tables per month compared with ∼2500 tables per month). Stabilis is now more complete to offer significant help to healthcare professionals with their problems of drug stability and compatibility.

A new approach to drug intravenous compatibility research: the case of obstetric parenteral drugs.

OBJECTIVES: The product information and literature does not provide confirmation of compatibility for co-administration of all commonly used drug pairs in obstetrics. However, there is a need for co-administration of these drugs over one lumen for this group of patients. Therefore, this study focuses on Y-site compatibility. Since different conditions between clinical and laboratory settings can lead to discrepancies in results, a novel approach for drug intravenous compatibility testing was designed to reflect clinical conditions. The aim was to study the compatibility of nine commonly used drug pairs in obstetrics and to evaluate the clinical value of the designed method. METHODS: The clinical situation was reflected by using different temperature ranges (20°C and 37°C), actual Y-site flow ratios, clinically relevant drug pairs and an observation time of 120 min. The clinically relevant drugs pairs include atosiban, nicardipine, amoxicillin/clavulanic acid, oxytocin, remifentanil, labetalol and magnesium sulpfate. Drug pairs were visually assessed according to the European Pharmacopoeia (Ph. Eur.) and pH was measured. When incompatibility of a drug pair seemed likely based on literature review or observed abnormalities during visual assessment, subvisual analysis was performed using a particle counter. Y-site compatibility applied for drug pairs when no visual changes occurred or when no additional particles were formed during the observation time. RESULTS: Eight of the nine combinations showed no visual changes or noticeable changes in pH during the observation time. The amoxicillin/clavulanic-acid-oxytocin combination showed a colour change at 37°C at the actual Y-site flow ratio. However, subvisual particle counting showed no formation of additional particles. CONCLUSIONS: Y-site compatibility was established for all tested drug pairs. The new clinical approach for analysing Y-site compatibility provides a high certainty of outcomes for clinical practice. In this way, clinical complications and use of several additional intravenous catheters can be avoided.

Container closure integrity testing and process validation of closed system transfer devices for aseptic reconstitution of drug vials connected to fluid bags.

OBJECTIVES: The closure integrity and process validation of closed system transfer devices (CSTDs) should be confirmed before implementation in clinical settings. We aimed to investigate the closure integrity and validate the aseptic procedure of two types of CSTDs by using a combination of the dye ingress test and a media fill test. METHODS: The dye ingress test with methylene blue was used for both CSTDs with 10 samples of drug vials of three brands. A media fill test was performed with both CSTDs (300 samples per CSTD, 150 carried out in a safety cabinet and 150 under non-classified environmental conditions). RESULTS: In all samples of both CSTDs, methylene blue was absent after visual inspection and spectrophotometric analysis. The nutrient media of one sample with CSTD A and none of the CSTD B samples were contaminated when reconstituted in a GMP grade A environment. Under non-classified environmental conditions, one sample of CSTD A and two samples of CSTD B were contaminated. CONCLUSIONS: Both CSTDs connected to the drug vials met the terms of closure integrity by using the dye ingress test. The aseptic procedure of CSTD B was validated with the media fill test when reconstituted in a GMP grade A environment, but failed for CSTD A. Both CSTDs failed the media fill test when reconstituted under non-classified environmental conditions.

Implementation of pharmacists' monitoring for intravenous drug compatibility.

BACKGROUND: Injectable medication errors primarily occur during preparation and administration. Currently, South Korea is experiencing chronic pharmacist shortages. Moreover, pharmacists have not routinely conducted prescription monitoring for intravenous compatibility. In the present study, we analysed the implementation of a pre-issue monitoring program using recently released cloud-based software to provide information on intravenous compatibility in the pharmacy at a general hospital in South Korea. OBJECTIVES: The aims of this study were to determine whether adding an intravenous drug prescription review to pharmacists' actual work scope could promote patient safety, and to assess the impact of this new task on pharmacists' workload. METHODS: Data on intravenous drugs prescribed in the intensive care unit and haematology-oncology ward were prospectively collected during January 2020. Four quantitative items were evaluated: the run-time, intervention ratio, acceptance ratio, and the information completeness ratio with regard to the compatibility of intravenous drugs. RESULTS: The mean run-time of two pharmacists was 18.1 min in the intensive care unit and 8.7 min in the haematology-oncology ward (p<0.001). Significant differences were also found between the intensive care unit and the haematology-oncology wards in terms of the mean intervention ratio (25.3% vs 5.3%, respectively; p<0.001) and the information completeness ratio (38.3% vs 34.0%, respectively; p=0.007). However, the mean acceptance ratio was comparable (90.4% in the intensive care unit and 100% in the haematology-oncology ward; p=0.239). The intravenous pairs that most frequently triggered interventions were tazobactam/piperacillin and famotidine in the intensive care unit, and vincristine and sodium bicarbonate in the haematology-oncology ward. CONCLUSION: This study suggests that despite a shortage of pharmacists, intravenous compatibility can be monitored before issuing injectable products in all wards. Because the prescribing pattern of injections varies across wards, pharmacists' tasks should be established accordingly. To improve the completeness of information, efforts to generate more evidence should continue.

Cross-sectional study of potential incompatibility of intravenous medications in a neonatal intensive care unit in Indonesia.

OBJECTIVE: The purpose of this study is to determine the most common incompatible and unknown compatibility drug combinations and determine the compatibility of each pair of drugs used in hospitals based on reference books and journals. METHODS: This is a prospective cross sectional study. All babies who were admitted to the Neonatal Intensive Care Units from May 1 to July 31 2021 were sample of the study. Patients who did not receive at least two drug coadministrated concurrently and who stayed less than 24 hours were excluded. Only drug-drug combinations were considered and the other non-drug administrations (electrolyte solutions, parenteral nutritions, and blood products) were excluded. Compatibility data were obtained from literature and online search engines [micromedex NeoFax Essentials 2020, UCL Hospitals Injectable Medicines Administration Guide: Pharmacy Department, 3rd Edition, Trissel Handbook on injectable drugs 15th edition, and published journals]. RESULTS: The most commonly prescribed drug combinations were ampicillin-gentamicin (31.72%), amikacin-ampicillin sulbactam (9.05%), amikacin-ampicillin sulbactam-aminophylline (3.08%). The most common drug incompatible combination was ampicillin - gentamicin (31.71%), for the most drug combinations whose compatibility unknown were amikacin-ampicillin sulbactam (9.05%). CONCLUSION: The high prevalence of incompatible drugs and unknown compatibility was identified, so checking its compatibility can be carried out through a two-dimensional chart to minimize the incidence of incompatibilities.

Cross-sectional study of potential incompatibility of intravenous medications in a Neonatal Intensive Care Unit in Indonesia. / [Artículo traducido] Estudio transversal de posibles incompatibilidades entre los medicamentos intravenosos en una unidad de cuidados intensivos neonatales de Indonesia.

OBJECTIVE: The purpose of this study is to determine the most common incompatible and unknown compatibility drug combinations and determine the compatibility of each pair of drugs used in hospitals based on reference books and journals. METHODS: This is a prospective cross-sectional study. All babies who were admitted to the Neonatal Intensive Care Units from May First to July 31st 2021 were sample of the study. Patients who did not receive at least two drugs coadministrated concurrently and who stayed less than 24 hours were excluded. Only drug-drug combinations were considered and the other non-drug administrations (electrolyte solutions, parenteral nutritions, and blood products) were excluded. Compatibility data were obtained from literature and online search engines (micromedex NeoFax Essentials 2020, UCL Hospitals Injectable Medicines Administration Guide: Pharmacy Department, 3rd Edition, Trissel Handbook on injectable drugs 15th edition, and published journals). RESULTS: The most commonly prescribed drug combinations were ampicillin-gentamicin (31.72%), amikacin-ampicillin sulbactam (9.05%), amikacin-ampicillin sulbactam-aminophylline (3.08%). The most common drug incompatible combination was ampicillin-gentamicin (31.71%), for the most drug combinations whose compatibility unknown were amikacin-ampicillin sulbactam (9.05%). CONCLUSIONS: The high prevalence of incompatible drugs and unknown compatibility was identified, so checking its compatibility can be carried out through a two-dimensional chart to minimize the incidence of incompatibilities.

Estudio transversal de posibles incompatibilidades entre los medicamentos intravenosos en una unidad de cuidados intensivos neonatales de Indonesia / Cross-sectional study of potential incompatibility of intravenous medications in a Neonatal Intensive Care Unit in Indonesia

Objetivo: el propósito de este estudio es determinar las combinaciones de medicamentos incompatibles y de compatibilidad desconocida más comunes y determinar la compatibilidad de cada par de medicamentos utilizados en los hospitales con base en libros de referencia y revistas.Métodosse trata de un estudio transversal y prospectivo. Todos los bebés que ingresaron en la unidad de cuidados intensivos neonatales del primero de mayo al 31 de julio de 2021 fueron muestra del estudio. Se excluyeron los pacientes que no recibieron al menos 2 medicamentos coadministrados y que permanecieron menos de 24 horas en la unidad. Solo se consideraron las combinaciones fármaco-fármaco y se excluyeron de este estudio las demás administraciones no farmacológicas (soluciones electrolíticas, nutrición parenteral y hemoderivados). Los datos de compatibilidad se obtuvieron de la literatura y los motores de búsqueda en línea (micromedex NeoFax Essentials 2020, la Guía de administración de medicamentos inyectables de los Hopitales de la UCL [University College London], Departamento de Farmacia, 3ª edición, el Manual Trissel sobre medicamentos inyectables, 15ª edición y revistas publicadas).Resultadoslas combinaciones de fármacos más prescritas fueron ampicilina-gentamicina (31,72%), amikacina-ampicilina sulbactam (9,05%), amikacina-ampicilina sulbactam-aminofilina (3,08%). La combinación medicamentosa incompatible más común fue ampicilina-gentamicina (31,71%), la mayoría de combinaciones medicamentosas cuya compatibilidad se desconocía fue amikacina-ampicilina sulbactam (9,05%).Conclusionesla alta prevalencia de fármacos incompatibles y de compatibilidad desconocida identificada, permite que la comprobación de su compatibilidad se pueda realizar a través de un gráfico bidimensional para minimizar la incidencia de incompatibilidades. (AU)

Objective: The purpose of this study is to determine the most common incompatible and unknown compatibility drug combinations and determine the compatibility of each pair of drugs used in hospitals based on reference books and journals.MethodsThis is a prospective cross-sectional study. All babies who were admitted to the Neonatal Intensive Care Units from May First to July 31st 2021 were sample of the study. Patients who did not receive at least two drugs coadministrated concurrently and who stayed less than 24 hours were excluded. Only drug-drug combinations were considered and the other non-drug administrations (electrolyte solutions, parenteral nutritions, and blood products) were excluded. Compatibility data were obtained from literature and online search engines (micromedex NeoFax Essentials 2020, UCL Hospitals Injectable Medicines Administration Guide: Pharmacy Department, 3rd Edition, Trissel Handbook on injectable drugs 15th edition, and published journals).ResultsThe most commonly prescribed drug combinations were ampicillin-gentamicin (31.72%), amikacin-ampicillin sulbactam (9.05%), amikacin-ampicillin sulbactam-aminophylline (3.08%). The most common drug incompatible combination was ampicillin-gentamicin (31.71%), for the most drug combinations whose compatibility unknown were amikacin-ampicillin sulbactam (9.05%).ConclusionsThe high prevalence of incompatible drugs and unknown compatibility was identified, so checking its compatibility can be carried out through a two-dimensional chart to minimize the incidence of incompatibilities. (AU)

Y-site administration of electrolyte solutions and injectable acetaminophen-A physical compatibility study with combinations frequently used in pediatric intensive care and anesthesia.

AIM: Determination of the physical compatibility of acetaminophen and two different electrolyte solutions (an isotonic, balanced electrolyte solution and a hypotonic, glucose containing electrolyte solution) with drugs frequently used in routine pediatric intensive care. METHODS: Analytical investigations for frequently used combinations without pre-existing data were performed. Visual and microscopic observations according to the European Pharmacopeia as well as pH measurements and ultraviolet visible spectrometry at wavelengths of 350, 410 and 550 nm were conducted to analyze physical compatibility. All measurements were performed immediately after mixing as well as 1, 4, and 24 h after. RESULTS: In total, 42 combinations were analyzed. Visual incompatibilities were found with pantoprazole and diazepam with both electrolyte solutions. For furosemide, a particle formation in mixture with the hypotonic glucose-containing electrolyte solution and a change in pH ≥ 0.5 after 24 h with both electrolyte solutions were observed. Ampicillin, cefuroxime, diazepam, furosemide, linezolid, meropenem, and pantoprazole showed an aberration of the absorbance ≥0.04 (350 nm/410 nm) or ≥0.01 (550 nm) in the photometric measurements with the electrolyte solutions. For acetaminophen, a physical incompatibility was observed with ampicillin, diazepam, furosemide, and pantoprazole. CONCLUSION: Most of the analyzed combinations showed no signs of physical incompatibility and may therefore be administered via the same Y-site. However, diazepam, furosemide, and pantoprazole should not be administered simultaneously with acetaminophen or both electrolyte solutions.

Investigation on the knowledge level of the rational application of antimicrobial drugs among pharmacists in medical institutions in Shanxi Province.

OBJECTIVE: To investigate the knowledge of the rational use of antibiotics among pharmacists in medical institutions in Shanxi Province, People's Republic of China, in order to determine the problems and provide support for the correct management of antibiotics. METHODS: A questionnaire survey was conducted, which included the basic information of the respondents, the basic knowledge of antimicrobial management, and the related knowledge of antimicrobial drugs. RESULTS: 462 pharmacists were investigated. The average score of the knowledge related to the rational use of antibiotics was 10.49±4.05. It showed that the hospital type, grade, pharmacist's education, professional title and working years all had an effect on the pharmacist's mastery of antimicrobial-related knowledge (p<0.05). Multivariate logistic regression analysis showed that hospital grade and pharmacist's education were the main influencing factors (p<0.05). CONCLUSION: Pharmacists have insufficient knowledge about the rational application of antibacterial drugs. It is essential to strengthen the training of management regulations and the application of antibacterial drugs.

Pancytopenia in a patient treated with fusidic acid and niraparib: a case report.

Fusidic acid is an antibiotic used in the treatment of staphylococcal infections. Niraparib is an anticancer drug indicated for the treatment of advanced ovarian cancer. The interaction between these two drugs has not been studied and is not referenced in drug databases. We present the case of a patient with pancytopenia who had been treated with fusidic acid and niraparib. No other treatment was taken by this patient. According to the literature, both substances can cause haematological toxicity. It seems unlikely that this is due to niraparib alone because it had been well tolerated by the patient for over a year before the pancytopenia was diagnosed. It was also perfectly well tolerated when it was reintroduced. We cannot determine whether this pancytopenia is due to fusidic acid alone or to a drug interaction between the two treatments. We therefore recommend caution in patients treated with this combination.

Stability and compatibility of admixtures containing bupivacaine hydrochloride and ketorolac tromethamine for parenteral use.

OBJECTIVE: Bupivacaine hydrochloride (BH) and ketorolac tromethamine (KT) are commonly used in parenteral admixtures to manage postoperative pain. However, stability and compatibility data for these admixtures applicable to current practice are limited, posing the patient to potential risk. METHODS: The stability of BH/KT admixtures in commonly used parenteral fluids was studied in Eppendorf tubes and glass vials at ambient room temperature using a newly developed and validated stability-indicating high-performance liquid chromatography (HPLC) method capable of the simultaneous quantification of both drugs. The chemical compatibility of BH/KT was assessed using Fourier transform infrared spectroscopy (FTIR) and thermal analysis. Additionally, the validity of the developed HPLC method for the quantification of BH/KT in human plasma was evaluated. RESULTS: BH and KT demonstrated <10% loss of their initial concentrations when prepared in Ringer, normal saline or dextrose solution at ambient temperature for up to 4 weeks. FTIR and thermal analysis demonstrated mild intermolecular interactions between BH and KT in solution, with no evidence of incompatibility. The developed HPLC method demonstrated satisfactory accuracy and precision for the simultaneous quantification of BH and KT in human plasma over the range of 0.2-3.2 µg·mL-1. CONCLUSION: BH/KT parenteral admixtures are chemically stable for a period of 4 weeks when stored at room temperature. The stability-indicating HPLC method is valid for BH/KT simultaneous determination in human plasma, facilitating pharmacokinetics studies.

Evaluation of 30-days stability of morphine hydrochloride and clonidine at high and low concentrations in polypropylene syringes.

OBJECTIVES: Clonidine is an alpha-2 adrenoreceptor agonist and is frequently combined with opioids (ie, morphine hydrochloride (HCl)) for the management of chronic pain. In palliative care, the administration of clonidine and morphine HCl is recommended in case of tolerance effect. This study aimed to evaluate the physical and chemical stability of this admixture at high and low concentrations in 14 and 48 mL polypropylene syringes. METHODS: The stability of a low concentration admixture of clonidine (Catapressan 0.15 mg/mL, Boehringer Ingelheim, Germany) and morphine (morphine HCl 40 mg/mL, Sterop, Belgium) at 0.003 and 0.417 mg/mL, respectively, was evaluated by using five polypropylene syringes of 48 mL. The high concentration admixture consisted of 0.032 mg/mL clonidine and 4.286 mg/mL morphine HCl and was evaluated by using five polypropylene syringes of 14 mL. All syringes were stored for 30 days at 5°C±3°C. Periodic samples were visually and microscopically examined to observe any particle appearance or colour change. pH and absorbance at three wavelengths (350, 410 and 550 nm) were monitored. The concentrations were measured by ultra-high performance liquid chromatography-photodiode array detection. RESULTS: During the 30 days, there was no change in colour or appearance of opacity, turbidity or precipitation, and pH remained stable. The low and high concentration admixtures were considered chemically stable since the lower limit of the 90% CI remained superior to 90% of the initial concentration. Concentration measurements showed that the degradation rate was less than 1% over 10 days for each component in both admixtures. CONCLUSIONS: The admixture of clonidine and morphine HCl at low and high concentrations in polypropylene syringes appeared to be physically and chemically stable throughout the study period of 30 days at 5°C±3°C. In conclusion, the admixture can be prepared in advance under aseptic conditions by a centralised intravenous additive service in the pharmacy department.

Visual compatibility and particle counter evaluations of syringes of intramuscular psychotropic coadministered solutions.

BACKGROUND: Patients in the acute phase of agitation can require the administration of multiple drugs by intramuscular injection in order to temporarily stabilise their condition. Administration of multiple psychotropic medications in a single syringe can be beneficial to both the patient and healthcare professionals. However, there are very little data in the literature regarding psychotropic drug compatibility in syringes for acute agitation. OBJECTIVE: The aim of this study was to assess the visual compatibility of various combinations of 12 intramuscular psychotropic medications in syringes, and to validate compatibility with the use of a particle counter. The medications evaluated were benztropine mesylate, diazepam, dimenhydrinate, diphenhydramine hydrochloride, haloperidol lactate, hydroxyzine, lorazepam, loxapine, methotrimeprazine, midazolam, olanzapine and zuclopenthixol acetate. METHODS: Compounded solutions of medication combinations underwent visual inspection initially and after 0.25, 0.5, 1, 2 and 4 hours using a white background and a black background. In order to validate the compatibility results, the presence of particulate matter was determined by light obscuration. RESULTS: This study identified 35 combinations that were visually compatible and 35 that were visually incompatible. We chose eight highly clinically relevant combinations to test using the requirements of the United States Pharmacopoeia (USP) chapter 788 (Particulate Matter in Injections). Of those eight, six were physically compatible, including the triple combinations of lorazepam and haloperidol with either benztropine or diphenhydramine. CONCLUSION: These physical compatibility results will give healthcare professionals an idea of the possible compatible combinations of psychotropic drugs in syringes, and thus complete some of the missing data in the literature.