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Background Deceased organ donations are rare in Japan, with most kidney transplants performed from a limited number of living donors. Researchers have thus developed highly successful ABO-incompatible transplantation procedures, emphasizing preoperative desensitization and postoperative immunosuppression. A recent open-label, single-arm, multicenter clinical study prospectively examined the efficacy and safety of rituximab/mycophenolate mofetil desensitization in ABO-incompatible kidney transplantation without splenectomy. Methods Mycophenolate mofetil and low dose steroid were started 28 days pretransplant, followed by two doses of rituximab 375 mg/m 2 at day −14 and day −1, and postoperative immunosuppression with tacrolimus or ciclosporin and basiliximab. The primary endpoint was the non-occurrence rate of acute antibody-mediated rejection. Patient survival and graft survival were monitored for 1 year posttransplant. Results Eighteen patients received rituximab and underwent ABO-incompatible kidney transplantation. CD19-positive peripheral B cell count decreased rapidly after the first rituximab infusion and recovered gradually after week 36. The desensitization protocol was tolerable, and most rituximab-related infusion reactions were mild. No anti-A/B antibody-mediated rejection occurred with this series. One patient developed anti-HLA antibody-mediated rejection (Banff 07 type II) on day 2, which was successfully managed. Patient and graft survival were both 100 % after 1 year. Conclusion Our desensitization protocol was confirmed to be clinically effective and with acceptable toxicities for ABO-I-KTx (University Hospital Medical Information Network Registration Number: UMIN000006635).

Purpose Physicochemical incompatibility (PCI) between drugs infused together is frequent, but under-recognized. PCI can lead to drug inactivity, catheter occlusion, embolism or inflammatory reactions. The aims of this work were to identify most frequent and relevant drug incompatibilities and to review and develop strategies for their prevention. Method This was an observational prospective survey conducted between January and March 2015 in an intensive care unit (ICU) and in September 2014 in a hematology sterile unit (HSU). Drugs administered to patients were recorded and their compatibility assessed based on published compatibility data. Results Drug incompatibilities accounted for 12% (23/189) and 17% (116/686) of drug pairs infused in the ICU and the HSU, respectively. Pantoprazole was the most frequent drug implied in PCI. Regarding drug classes, anti-infective agents and gastrointestinal drugs were the most frequently implied. Among the incompatible pairs, 78% and 61% implicated a drug with extreme pH in the ICU and HSU, respectively. The tools proposed to reduce the frequency of PCI included: compatibility cross-tables, labeling of drugs with extreme pH and optimized administration schedules. Conclusions Given the frequency and the potential for severe consequences of PCI, pharmacists have a role to play in raising awareness of nurses and practitioners, and proposing adequate tools and solutions to reduce their incidence.

Patients hospitalized in intensive care unit (ICU) commonly use a number of drugs intravenously. These patients often require antimicrobial therapy. The precipitation, inactivation, and change in stability caused by concurrently administering two or more drugs can reduce drug efficacy and lead to a low therapeutic effect that is detrimental to antimicrobial therapy. The aim of this study was to identify possible incompatibilities that include antimicrobial agents. This cross-sectional and prospective study was conducted between August 17–November 30, 2022 in ICU of the Department of Internal Medicine. Drug request lists (DRL) that include at least one antimicrobial drug of patients aged 18 and over with an ICU stay period equal to or longer than 24 h were evaluated. Identical DRLs of the same patient were excluded. Possible incompatibilities of IV drugs administered to patients were assessed using the IBM Micromedex® and Stabilis 4.0 databases. The incompatibilities classified as “incompatible” or “variable compatibility” have been identified by the clinical pharmacy residency student. Recommendations were shared verbally and in writing with physicians and nurses. Possible drug incompatibility problems were prevented by immediate intervention. Seven hundred two DRLs of a total of 65 patients (51.16% female; 76.2 ± 14.9 years; 4.15 ± 1.68 comorbidities) were analyzed; 301 DRLs met the inclusion criteria. Nearly 29% of all drugs were antimicrobials averaging 2.1 ± 1.74 (max: 6). The most commonly used anbtimicrobials were meropenem, teicoplanin, piperacillin/tazobactam, colistimethate sodium and micafungin. The presence of possible incompatibility was detected in 73.75% of the DRLs. There was a positive correlation between the number of antimicrobials and possible incompatibilities (rho = 0.212; p = 0.0002). Of all drug-drug incompatibilities, 23.52% were associated with antimicrobials. Possible incompatibilities most frequently included meropenem, piperacillin/tazobactam, gentamicin, levofloxacin and micafungin. Meropenem and pantoprazole were the most common pair of drugs with possible incompatibility. Of specific importance, all drug-solution incompatibilities were associated with antimicrobials. These agents were caspofungin, daptomycin, meropenem and amphotericin B liposomal. The clinical pharmacy residency student stated 262 suggestions related to antimicrobials. All of them have been accepted and implemented. This study documented a high risk for incompatibilities not only between two drugs, but also between a drug and the solution. In addition, as an essential component of treatment at ICU, antimicrobial drugs require a specific attention in this regard. Some of these may be eliminated by a priori examination of a clinical pharmacist.

Drug incompatibilities are considered as one of the most critical problems in intensive care units. In the current study, the ability of nanomaterials to prevent drug incompatibilities in clinical settings has been investigated. As a proof-of-concept, the ability of niosomes to prevent physical and chemical incompatibilities that occur upon mixing acyclovir and vancomycin during management of acute meningitis has been explored. Nanosized spherical particles loaded separately with either vancomycin or acyclovir, with high entrapment efficiency ( ca . 46–56%), could be prepared, and sustained release of their entrapped cargoes have been demonstrated over time. We have shown that precipitation, degradation and loss of biological activity of drugs occurred upon mixing solutions of the free drugs. On the contrary, drugs loaded separately inside niosomal structures exhibited high stability, exceptional physical and chemical compatibilities for up to 48 h with complete preservation of the antimicrobial activity of vancomycin. This study opens a venue for a new spectrum of applications of nanomaterials in preventing clinically significant drug incompatibilities, aiming at the reduction of adverse reactions, cost and hospitalization period, and improvement of patient compliance and therapeutic outcomes.

Background/Objectives: Multi-lumen devices that limit physicochemical incompatibilities (PCIs) are frequently used in neonatal intensive care units where premature infants receive numerous infusions. The aim of the study was to investigate a PCI that occurred despite the use of a device of this type (EDELVAISS® Multiline NEO, Doran International, Toussieu, France). Case Summary: A 7-week-old preterm infant received ganciclovir at therapeutic dosage for cytomegalovirus (CMV) infection. After the fifth administration of ganciclovir, a PCI occurred, leading to a white precipitate. The peripheral inserted central catheter (PICC) (PREMICATH®2Fr, Vygon, Ecouen, France) had to be replaced. Laboratory reproduction of the administrations during 72 h, nuclear magnetic resonance (NMR) analysis and particle counting were carried out to analyse the occurrence of events leading to PCIs. The precipitate was linked to a PCI of parenteral nutrition associated with a dilution error of ganciclovir (omission of a 10-fold dilution step, resulting in ganciclovir being administered at 30 mg/L instead of 3 mg/L). Due to the presence of lipids in the parenteral nutrition, visual detection of the white precipitate was difficult. Conclusions: Multi-lumen infusion devices limit but do not prevent the occurrence of PCIs, particularly in the event of a preparation error. Despite the use of this type of device, great vigilance is still required, particularly with regard to prescription analysis and reconstitution procedures.

•Assessed the physical compatibility of reduced glutathione for injection with 44 intravenous drugs during simulated Y-site administration.•Found reduced glutathione for injection to be physically incompatible with 11 of 44 intravenous drugs over a 4-hour period.•Observed immediate formation of a flocculent mixture when combined with acyclovir.•Detected an immediate Tyndall effect when mixed with diazepam, dexmedetomidine hydrochloride, and other intravenous drugs. Reduced glutathione (GSH) is extensively used in clinical therapeutics due to its antioxidative and cytoprotective properties. It is essential in the management of various chronic and acute conditions and serves as an adjunct therapy in oncology. Despite its widespread use, the physical compatibility of GSH with other intravenous drugs during Y-site administration has not been thoroughly investigated, posing risks such as reduced efficacy and adverse reactions. This study fills this critical gap by examining the physical compatibility of GSH with 44 commonly used intravenous drugs in simulated Y-site administration with 0.9% sodium chloride injection (NS) and 5% dextrose injection, aiming to enhance patient safety and clinical outcomes. Simulated Y-site administration was conducted in vitro by mixing 24 mg/mL of GSH with equal volumes of 44 diluted intravenous drugs. Physical compatibility was assessed by observing visual changes, checking for the Tyndall effect, measuring turbidity, and monitoring pH levels at 0, 0.5, 1, 2, and 4 hours post-mixing. Physical compatibility was defined as the absence of color changes, gas evolution, particulate formation, and the Tyndall effect within 4 hours, with turbidity changes of less than 0.5 nephelometric turbidity units from baseline and pH variations of less than 10% from initial values. GSH exhibited physical incompatibility with 11 of the 44 intravenous drugs evaluated, while it remained compatible with 33 drugs over 4 hours. This study reveals that while GSH is physically compatible with the majority of tested intravenous drugs, incompatibilities with 11 drugs under simulated Y-site conditions necessitate rigorous compatibility testing prior to co-administration in clinical settings. These findings emphasize the importance of such testing to prevent potential treatment failures and adverse effects. Further research is needed to explore chemical stability and therapeutic efficacy in clinical settings, ensuring the safe and effective use of GSH in medical treatments.

In pediatric practice, nalbuphine hydrochloride can be administered by continuous infusion through a multiport manifold or Y-site connection over 24 h in a 60 mL polypropylene syringe unprotected from light at concentrations ranging from 52.1 µg.mL -1 to 333.3 µg.mL -1 in normal saline (NS). To limit the need for multiple injections, nalbuphine hydrochloride may be co-administered with other drugs. Its stability and compatibility were already studied at concentration ranges equal or higher than 1.0 mg.mL -1 . However, when nalbuphine hydrochloride needs to be diluted for a pediatric administration its stability in NS over 24 h of light exposure at ambient temperature and its compatibility with other drugs have never been studied before. A novel chromatographic method using high-performance liquid chromatography (HPLC) was validated by the International Council for Harmonisation (ICH) Q2 (R1) guidelines. The stability of nalbuphine hydrochloride and the appearance of degradation products under five experimental conditions (light, heat, oxidation, basicity, and acidity) were monitored by HPLC-UV for 24 h at ambient temperature at three concentrations administered in pediatric departments (52.1 µg.mL -1 , 166.7 µg.mL -1 and 333.3 µg.mL -1 ). The physical compatibility of nalbuphine hydrochloride with 1:1 (v/v) mixtures of selected drugs used in pediatrics was evaluated by visual inspection and with a 10 µm and 25 µm sub-visible particle counter. Our nalbuphine hydrochloride quantification method has been validated and was stability-indicating. The stability of nalbuphine hydrochloride and the forced degradation assay (light, heat, oxidation, basicity, and acidity) studied for the three concentrations of nalbuphine hydrochloride diluted in 48 mL of NS and stored in a 60 mL polypropylene syringe unprotected from light were compliant for at least 24 h at ambient temperature. Nalbuphine hydrochloride in NS was found to be compatible with several drugs, but was incompatible with furosemide and amphotericin B. Nalbuphine hydrochloride can be administered in pediatric practice using a syringe pump for 24 h. However, drug-drug incompatibilities need to be considered when it is administered through a multiport manifold or Y-site connection.

Amiodarone and furosemide are frequently administered together in the intensive care unit, and their co-administration poses a risk of precipitation and catheter occlusion due to incompatibility. Thus, compatibility should be evaluated under clinically relevant conditions to ensure safe drug administration. This study investigated the impact of different mixing procedures on the physical compatibility of amiodarone and furosemide by employing two clinically relevant approaches: simulated mixing (SM) and route mixing (RM). Mixtures were prepared at therapeutic concentrations and evaluated by visual inspection, absorbance measurement, powder X-ray diffraction (PXRD), pH analysis, and particle size assessment. Although the drug ratios were identical, the RM samples displayed greater turbidity than the SM samples. The PXRD analysis showed no formation of new crystalline substances, and the precipitates consisted of known furosemide and amiodarone hydrochloride polymorphs. The pH shifted toward the alkaline range as the injection volume increased with furosemide dose. Importantly, differences in particle growth behavior were noted between SM and RM, with larger particles observed in the RM samples. In conclusion, mixing route significantly affects drug compatibility, with RM presenting a higher risk of precipitation. Assessing drug compatibility under clinically relevant conditions may help prevent catheter-related complications and improve the safety of intravenous pharmacotherapy.

•A rapid, precise, and efficient HPLC method was successfully developed for the determination of drug contents in a mixed solution containing 6 common cephalosporins and ciprofol.•Both diluents (0.9% sodium chloride and 5% glucose solution) maintained optimal physicochemical stability for all compatibility solutions throughout the 8-hour observation period.•The 5% glucose diluent showed superior zeta potential and drug retention versus saline under clinical simulations, supporting its selection for prolonged infusions to optimize formulation stability. Simultaneous administration of multiple drugs via Y-site infusion is a common practice during the perioperative period; however, in-line incompatibility remains a significant safety concern. Ciprofol injection, a novel intravenous anesthetic based on lipid emulsifiers, may exhibit compromised stability when co-administered with other medications. This study systematically evaluated the compatibility and stability of ciprofol injection with 6 commonly used cephalosporins (cefazolin, cefuroxime, cefradine, cefotaxime, ceftriaxone, and cefoperazone) during Y-site infusion to ensure the safe and rational use of perioperative intravenous therapies. Ciprofol injection was mixed with clinically relevant concentrations of 6 cephalosporins in 0.9% sodium chloride or 5% glucose solution at a 1:1 volume ratio under ambient conditions (25 ± 1°C). Samples were collected at predetermined time points (0, 2, 4, 6, and 8 hours) for comprehensive evaluation of physical and chemical properties, including appearance, pH value, Zeta potential, particle size/polydispersity index (PDI), osmotic pressure, and relative percentage content changes of the mixtures. Within an 8-hour period, no visible changes in the appearance of any drug mixture were observed. The pH values fluctuated within ±0.5, while the average particle size remained stable at (215 ± 10) nm with uniform particle size distribution (PDI = 0.12 ± 0.04). The Zeta potential and osmotic pressure values exhibited stability throughout the study period. The relative drug content was maintained between 95% and 105%. Microscopic imaging analysis showed that there was no aggregation of milk droplets or abnormal increase of particle size in the mixture. Under conditions of room temperature, ciprofol injection demonstrated compatibility and stability when administered via Y-site infusion with 6 commonly used cephalosporins at clinical dosage concentrations for up to 8 hours. These findings provide valuable guidance for the safe and effective use of ciprofol in perioperative settings.

•Intravenous drug compatibility testing is important for patient safety.•The interactions of fluconazole and 6 parenteral nutrition admixtures were studied.•Particle size, zeta potential, turbidity, pH, and osmolality measurements performed.•The studied intravenous preparations were found to be compatible. [Display omitted] Fluconazole (FLZ) is a drug widely used in the treatment of fungal infections including the treatment of immunocompromised patients, HIV-infected patients, and cancer patients. Critically ill patients often require the administration of drugs with parenteral nutrition (PN). The safety of this combination should be defined before the drug and PN are administered in one infusion line. This study aimed to determine the compatibility of FLZ with six selected multichamber bag parenteral nutrition. FLZ solution for infusion was combined with PNs in appropriate proportions, considering most clinical situations resulting from different possible administration rates of the preparations. Samples were visually assessed, and pH, osmolality, turbidity, particle size (dynamic light scattering and light obscuration methods), and zeta potential were measured. These measurements were made immediately after combining the solutions and after 4 h of storage at 23 ± 1°C. FLZ combined with PNs did not cause changes observed visually. The turbidity of the samples was <0.4 NTU. The average particle size of the lipid emulsion was below 300 nm, and the PFAT5 parameter was ≤0.02%. The absolute value of the zeta potential of the PN + FLZ samples was higher for 5 out of 6 PN than the corresponding value for PN immediately after activation. Changes in pH and osmolality during 4 h of sample observations were within acceptable limits. Compatibility of the FLZ with six multichamber bag PN was confirmed. Hence, those preparations can be administered to patients in one infusion line using the Y-site.