SAFETY AT THE RIGHT DOSE: THE PHARMACIST’S INTERVENTION IN THE PREVENTION AND TREATMENT OF IFOSFAMIDE-INDUCED ENCEPHALOPATHY
European Statement
Clinical Pharmacy Services
Author(s)
Vera Pires, Maria João Teixeira, Rui Marques
Why was it done?
Ifosfamide-induced encephalopathy (IIE) is a serious and often underdiagnosed adverse effect of ifosfamide, with variable incidence and no standardized approach to prevention or treatment. The project aimed to improve patient safety and clinical outcomes by developing a standardized, evidence-based institutional protocol to guide prophylaxis and management of IIE.
What was done?
An institutional protocol for the prevention and treatment of IIE was developed and implemented, defining clear recommendations for methylene blue and thiamine use, standardizing dosing regimens, and providing practical instructions for clinical teams.
How was it done?
A comprehensive literature review was carried out, current local practices were analyzed, and a multidisciplinary team collaborated to design the protocol. The final version was reviewed and approved by the Pharmacy and Therapeutics Committee (PTC) before implementation.
What has been achieved?
The protocol reduced variability in prescribing practices, increased medication safety, and enhanced the pharmacist’s involvement in monitoring and managing adverse events. It established consistent dosing, preparation, and administration procedures for both adult and pediatric patients, improving overall care quality and coordination.
What next?
The next step is to evaluate the clinical and organizational impact of the protocol from both patient and institutional perspectives, with a focus on outcomes such as incidence reduction, safety indicators, and staff adherence.
IMPROVING INTRAVENOUS CHEMOTHERAPY ADMINISTRATION SAFETY VIA SMART INFUSION TECHNOLOGY: ONE-YEAR IMPLEMENTATION AT HYGEIA HOSPITAL
European Statement
Patient Safety and Quality Assurance
Author(s)
IOANNIDIS KONSTANTINOS
SCARLATINIS IOANNIS
KORRE OURANIA
BOTSIOU MARIA
NIKOLAOU KATERINA-ANGELIKI
Why was it done?
The integration of clinical pharmacists in oncology settings plays a critical role in ensuring the safe and effective administration of chemotherapeutic agents. At Hygeia Hospital, over the past five years, clinical pharmacists have identified and prevented 1,272 chemotherapy-related medication errors, corresponding to 2.4 errors per 100 chemotherapy days. Despite this substantial contribution, challenges persist in the administration process by nursing staff, particularly regarding infusion parameters. Common errors include incorrect infusion rates and the omission or improper use of required filters and light-sensitive infusion sets, and their prevention remains a persistent challenge.
What was done?
To mitigate these risks, Hygeia Hospital has implemented parameterized electronic infusion pumps as an additional safety mechanism.
How was it done?
These pumps are pre-programmed by clinical pharmacists with non-modifiable infusion time limits for each chemotherapeutic agent, preventing unauthorized alterations by nursing personnel. Furthermore, the pumps provide mandatory prompts regarding the use of filters or/and light sensitive infusion sets, as specified in the Summary of Product Characteristics (SPC) of each drug.
What has been achieved?
Since their introduction one year ago, these infusion pumps have facilitated the identification and correction of previously undetectable administration errors, with an observed rate of 0.15 errors per 100 chemotherapy days. The majority of these involved incorrect selection of infusion duration by nursing staff. These findings underscore the value of pump parameterization in uncovering latent errors and reinforcing adherence to safe administration practices.
What next?
Future steps include expanding the use of parametrized infusion pumps beyond oncology to other high-risk areas, such as intensive care units, where precise and safe administration is equally critical. By reducing reliance on manual intervention and standardizing administration protocols, this approach enhances the overall safety and efficacy of drug delivery across multiple clinical settings.
STABILITY STUDY OF CONCENTRATED AMOXICILLIN IN RINGER’S LACTATE SOLUTION: AN ALTERNATIVE TO NACL 0.9% TO REDUCE THE RISK OF CRYSTALLURIA?
European Statement
Production and Compounding
Author(s)
K. Lefèvre (1), Vincent Dubée (2,4), Vincent Lebreton (1,3)
(1) Angers University hospital center, Pharmacy Department, Angers, France
(2) Angers University hospital center, Infectious diseases Department, Angers, France
(3) MINT Inserm 1066, CNRS 6021, University of Angers, France
(4) INCIT-Atomyca, UMR 1302/ERL 6001, University of Angers, France
Why was it done?
Amoxicillin (AMX) is a widely used antibiotic, particularly for severe infections requiring high-dose intravenous administration. The two commonly used solvent are 0.9% NaCl (NaCl) and Ringer’s lactate (RL). NaCl may have been associated with cases of crystalluria following hyperchloremic acidosis, leading to impaired renal function. So RL may be considered as a promising alternative, although stability data are lacking.
What was done?
This study aimed to evaluate and compare the stability of AMX in both solvents at different concentrations for 12h at room temperature.
How was it done?
To evaluate AMX stability, injectable AMX was reconstituted according to the product’s specification and diluted in RL or NaCl. Four concentration levels were prepared (10, 12, 15, 20 mg/mL), stored in a climate-controlled chamber (25±2°C; 65± 5%RH) and analysed at various time intervals (0, 3, 6, 9, 12 hours). The study was conducted with a stability indicating method using reverse-phase high-performance liquid chromatography coupled with diode array UV (250 nm) and mass spectrometry detection. The method validation followed ICH guidelines (Q2R2, Q6A, Q3B). Organoleptic characteristics and pH were also monitored.
What has been achieved?
AMX concentrations remained above 90% of the initial value throughout the 12-hours period, regardless of solvent or concentration. However, the chromatograms reveal additional peaks suggesting the formation of degradation products in both NaCl and RL. These degradation products were quantified (maximum% of main peak surface area) and identified [letter corresponding to European Pharmacopeia identification] as penicilloic acid (4.5) [D], phenylpyrazine (1.3) [F], diketopiperazine (1.8) [C], amoxicillin dimers (6.5) [J] and and adduct species of them (Na+ and K+) (0.5). Despite these findings, there were no notable changes in the appearance or color of the solutions, and pH remained relatively stable, decreasing slightly from 8.8 to 8.6.
What next?
The study concluded that while AMX concentrations stayed relatively stable, some of the identified degradation products exceed limits set by ICH Q3B guidelines and European Pharmacopeia for degradations products in both solvents. Therefore, the results should be interpreted cautiously, pending further toxicological and regulatory assessments. If the degradations products are deemed acceptable, Ringer’s lactate could be a clinically viable alternative to NaCl, especially for high-dose AMX infusions, due to its lower sodium content and buffering effect, which helps reduce the risk of metabolic acidosis.
INHALATION GENE THERAPY: PROTECTIVE EQUIPMENT IMPLEMENTED
European Statement
Production and Compounding
Author(s)
Scarlett Wise, Pharmacy
Sandrine Gotty, Infectious risk prevention
Sylvain Auvity, Pharmacy
Robert Ratiney, Pharmacy
Caroline Chirk, Pharmacy
Aude Boyer, Clinical investigation center
Why was it done?
Inhalation GTMP’s nature are various, such as mRNA vectorized in lipid nanoparticles and virus GMO therapies. Hospital staff needs reassurance and protective equipment (PE) facing the management of these new ATMPs.
What was done?
Before administrating a new advanced therapy medicinal product (ATMP), including gene therapy medicinal product (GTMP), precaution measures must be implemented for the safety of health care personal at every step of the pharmaceutical process. Administration of GTMP by inhalation generates volatile active substance particles in the air during and after inhalation.
As a result, protection measures were established to secure hospital personal during administration and all through patient hospitalisation.
How was it done?
The dedicated ATMP pharmacist and healthcare manager, identified each key parameter: GTMP nature, persistence on surfaces and types of contamination: airborne, droplet or contact.
The exposition phases in patient’s room were cut down to 3 periods:
1) Administration and instant post administration
2) Hospitalisation post administration
3) Patient discharge
For each period, precautionary measures for entering and exciting patients’ room were discussed:
a. PE
b. Safety distance between personal and patient
c. Bio-cleaning
d. Waste management
Isolation signs for each ATMP were created, approved by the hygiene department and displayed at the entrance of every patient’s room. These signs summarized the good behaviour for every period and detailed the necessary PE.
What has been achieved?
Two isolation signs were created: mRNA and virus-vectorized GTMP.
For 1st period:
Entering: FFP2 mask (airborne), gown, covering glasses, mobcap, gloves and 1.5m distance during administration were identified for both GTMPs. Virus-vectorized GTMP required additional doubled gloves, overshoes and disposable pants.
Room exit: all objects needed decontamination when brought out of patient’s room (contact) for virus-vectorized GTMP.
For 2nd period:
Entering: surgical mask, gown and gloves were identified for both GTMPs. Virus-vectorized GTMP required a surgical mask for the patient (droplets).
For 3rd phase: floor and wall bio-cleaning were necessary and furniture for virus-vectorized GTMP. PE was thrown away in usual waste for mRNA. For virus-vectorized GTMP, PE follows biohazard waste and laundry is identified.
Room exit in all periods required hand washing with hydroalcoholic solution.
What next?
Isolation signs will be created to accompany each new ATMP handling and administration.
DETERMINATION OF THE PH OF SELECTED ANTI-INFECTIVES FOR SAFE INTRAVENOUS ADMINISTRATION
European Statement
Clinical Pharmacy Services
Author(s)
L. Čermanová, V. Slezáková, J. Babiaková, D. Fábiánová, S. Porubcová
Why was it done?
Phlebitis is one of the most common complications of infusion therapy. Intravenous drugs with extreme pH values (9) may chemically irritate or damage the venous endothelium, triggering an inflammatory response. Understanding the pH of intravenous anti-infectives is essential for clinical decision-making to prevent infusion-related complications.
What was done?
The aim of this work was to determine the pH values of selected intravenous anti-infectives administered at the National Institute of Cardiovascular Diseases, Bratislava (NÚSCH, a. s.) due to their potential to cause endothelial damage.
How was it done?
A literature review was performed to collect available data on the pH of reconstituted and diluted anti-infectives used at NÚSCH, a. s. Sources included Summaries of Product Characteristics, ASHP Injectable Drug Information®, pharmaceutical recommendations of Hôpitaux Universitaires de Genève, and relevant scientific publications.
The criteria used to select anti-infectives for pH analysis were a complete lack or insufficient information on the drug’s pH, reported pH values approaching the extreme thresholds of 5 or 9, and excessively wide pH ranges exceeding these limits.
Subsequently, the pH of 21 selected drugs was measured at 37 commonly administered concentrations (including ready-to-use formulations) using a glass-electrode pH meter (XS pH 7 Vio portable pH meter; electrode CHS ChemFlex). The diluents used were 0.9% sodium chloride solution, 5% glucose solution, and water for injection.
What has been achieved?
A table summarising selected anti-infectives at commonly administered concentrations, along with their mean pH values (± standard deviation) was compiled. Dilution volumes used in clinical settings with either 0.9% sodium chloride or 5% glucose solution for extremely acidic or alkaline medications did not appear to significantly modify pH in a way that would affect vascular access choice.
The pH values enable the identification of anti-infectives with a higher potential risk of phlebitis and support the selection of the most appropriate vascular access device.
What next?
The results will be applied in developing institutional recommendations for the dilution and administration of anti-infectives, supporting safer infusion practices and the prevention of chemically induced phlebitis across NÚSCH, a. s. wards. They will also inform staff training and may contribute to the reduction of medication errors.
THE CRUSHING FACTORY SAFE PHARMACOTHERAPY THROUGH ENTERAL FEEDING ACCESS – EXPERIENCES AND GOOD PRACTICES FROM THE UNIVERSITY CLINICAL CENTRE IN GDAŃSK
European Statement
Clinical Pharmacy Services
Author(s)
Ewelina Lubieniecka – Archutowska, Bogusława Szmaja, Dorota Świtkowska, Agnieszka Prusko, Magdalena Jaśkowska, Marzena Mielczarek – Kęska, Urszula Dobrzycka – Magulska, Wioletta Kaliszan
Why was it done?
Enteral nutrition therapy plays a crucial role in the management of patients who cannot meet their nutritional needs orally. Besides providing essential nutrients, enteral feeding access often serves as a route for drug administration, which requires specific knowledge about drug compatibility and pharmacotherapy safety among healthcare professionals.
The aim of this project was to improve the safety and effectiveness of pharmacotherapy administered through enteral feeding access at the University Clinical Centre in Gdańsk (UCC).
What was done?
Based on literature review and institutional experience, the main challenges identified were related to the selection of appropriate medicines and pharmaceutical forms, as well as to the preparation and administration techniques used by nursing staff. To address these issues, several measures were implemented within UCC to enhance pharmacotherapy safety in patients with artificial enteral access.
How was it done?
A procedure titled “Principles of Administering Medicinal Products to Patients Receiving Enteral Nutrition via Feeding Tube or Gastrostomy” was developed and implemented. Within the hospital information system (Clininet), a dedicated list of medicines that must not be crushed or administered via enteral routes was introduced and made visible to physicians and nurses to support safe prescribing. Clininet also allows physicians, nurses, and dietitians to request pharmacotherapeutic consultations from hospital pharmacists. Pharmacists analyze and, when necessary, modify patients’ therapy. Medicines suitable for administration through enteral access were added to the hospital formulary, enabling physicians to choose formulations appropriate for crushing or alternative routes of administration. The hospital pharmacy introduced the so-called “Crushing Factory” – a centralized service where pharmacists prepare R.PEG-labeled medicines in safe forms and doses for enteral administration. Each administration is recorded in the patient’s medical documentation.
What has been achieved?
The implemented system led to:
• fewer prescribing and administration errors
• reduced drug loss and preparation mistakes
• fewer interactions and adverse effects
• compliance with accreditation standards for medication safety
• lower treatment costs and fewer pharmacological interventions
• reduced nursing workload and improved efficiency
What next?
Expand staff education on enteral pharmacotherapy, standardize training materials, monitor outcomes, introduce patients pharmaceutical discharge summaries and implement solutions hospital -wide to improve safety and continuity of care.
PHARMACOKINETIC-GUIDED HIGH-DOSE METHOTREXATE PROTOCOL: MULTIDISCIPLINARY COLLABORATION AND OUTCOMES IN REAL-WORLD PRACTICE
European Statement
Clinical Pharmacy Services
Author(s)
Anais Carrillo Burdallo
Cristina Villanueva Bueno
Maria del Pilar Montero Antón
Isabel Regalado-Artamendi
Beatriz Torroba Sanz
Jose Luis Revuelta Herrero
Eva González-Haba Peña
Daniel Gomez Costas
Yeray Rioja Díez
Antonio Prieto Romero
María Martín Bartolomé
Xandra García Gonzalez
Ana Herranz Alonso
Maria Sanjurjo Saez
Why was it done?
High-dose methotrexate (HD-MTX) carries substantial toxicity risk. Safety hinges on timely, appropriately dosed leucovorin rescue plus high-volume hydration and urinary alkalinisation. Pharmacokinetic monitoring with proactive follow-up enables early detection of delayed clearance and better-informed decisions.
What was done?
A protocol for the administration and pharmacokinetic monitoring of HD-MTX was developed and implemented in a tertiary hospital in coordination with the Haematology Department.
How was it done?
Standardised procedures for administration were defined (hydration/alkalinisation strategies; rescue timing/dose; infusion start; sampling schedule). Adults with leukaemia/lymphoma received short (5µmol/L; long: 42h, >1µmol/L).
Pharmacist-led interventions were classified as: enhanced elimination (intravenous fluids/furosemide; bicarbonate/acetazolamide; cholestyramine), rescue optimisation (dose guided by the prediction, readjusted after the measured level, and withheld when appropriate), and monitoring (additional levels and duration).
Continuous accuracy was assessed with the individual percentage error (IPE)=[(predicted−observed)/observed]×100; we report MDIPE (median IPE; accuracy), MAIPE (median absolute IPE; precision), and the proportion within 1.5-fold. Classification against thresholds was summarised with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).
What has been achieved?
In 24 administrations (13 short, 11 long), pharmacist-led interventions were implemented in every cycle: enhanced elimination 88%, rescue optimisation 54%, monitoring 71%.
Continuous accuracy: MDIPE +35% (IQR 9–80), MAIPE 38% (IQR 11–80); 54% within 1.5-fold. Threshold performance (short/long): accuracy 69/91%; sensitivity 100/100%; specificity 67/86%; PPV 20/80%; NPV 100/100%.
Protocolised monitoring improved safety by standardising decisions and reducing errors. The predictive tool achieved 100% sensitivity and NPV, supporting early rule-out of delayed clearance; positive alerts should be interpreted cautiously given moderate overprediction and false positives near thresholds, with confirmation and close follow-up.
What next?
Next steps are full rollout, recalibration and threshold tuning in larger cohorts, and extension to Oncology and Paediatrics, tracking efficiency endpoints (time to <0.05-0.2 µmol/L, length of stay).
MEDICATION ERROR IN A CLINICAL TRIAL: ROOT CAUSE ANALYSIS AND IMPROVEMENT ACTIONS
European Statement
Patient Safety and Quality Assurance
Author(s)
Cristina Garcia Fernandez, Estela Alamino Arrebola, Bárbara Lopez Bautís, Carmen Gallego Fernandez, Begoña Tortajada Goitia.
Why was it done?
Patient safety in clinical trials relies on the correct management of both investigational and auxiliary/comparator medications. While investigational products are usually managed through automated systems (e.g., IWRS) ensuring traceability and standardization, auxiliary medications often lack similar oversight from sponsors. A preventable medication error in an oncology clinical trial—caused by the preparation of an incorrect drug concentration due to the absence of automated supply and harmonization—highlighted the need to analyze system gaps and implement corrective actions to strengthen patient safety and medication traceability.
What was done?
A Root Cause Analysis (RCA) was conducted following the detection of a medication error involving the preparation of hospital stock (20 mg/mL) instead of the clinical trial formulation (10 mg/mL). The objective was to identify systemic weaknesses and design a Corrective and Preventive Action (CAPA) plan aimed at preventing recurrence and improving management of auxiliary medication in clinical trials.
How was it done?
The RCA was performed in July 2025 using the “5 Whys” methodology, supported by:
-Document review, staff interviews, and chronological reconstruction of the event.
-Analysis of human, technical, communicative, and organizational factors.
-Classification of the incident (NCC MERP category D — no patient harm).
Corrective measures implemented included:
– Creation of a pre-trial pharmacy checklist to ensure drug availability and concentration verification.
– Mandatory pharmaceutical validation after any protocol amendment.
– Formal requests to sponsors to standardize drug concentrations across sites.
– Improved communication channels between sponsors, pharmacy, and clinical teams
What has been achieved?
-Identification of the main root cause: lack of automation in auxiliary drug supply requiring manual requests.
-Prevention of similar future events through harmonized pharmacy processes.
-Reinforcement of patient safety culture and traceability of clinical trial medications.
-Strengthened collaboration among hospital pharmacy, clinical teams, and sponsors.
-No patient harm resulted from the event, confirming the importance of early detection and system review.
What next?
-Extend IWRS automation and standardization practices to include auxiliary medications in all clinical trials.
-Share the initiative with other hospital pharmacies and sponsors to promote harmonization at institutional and multicenter levels.
-Continue monitoring the implemented CAPA and evaluate its impact on error prevention.
-Foster continuous improvement in pharmacy oversight and communication workflows for clinical research.
IMPLEMENTATION OF A MULTIDISCIPLINARY PROTOCOL FOR CAB/RPV IM IN HIV CARE
European Statement
Patient Safety and Quality Assurance
Author(s)
A. VARAS PEREZ1, MJ. LOPEZ MUÑOZ1, C. RODRIGUEZ MORETA1.
1HOSPITAL SERRANIA DE RONDA, FARMACIA, RONDA, SPAIN.
Why was it done?
Long-acting injectable antiretroviral therapy represents a major advancement in HIV management. This method of administration is novel, and as such, a process must be defined that involves different healthcare professionals and that must provide the patient with the training related to the administration in the best way. The intramuscular combination of cabotegravir and rilpivirine (CAB/RPV IM) offers an alternative to daily oral regimens, potentially improving adherence and patient quality of life. To ensure safe and efficient implementation, a multidisciplinary protocol was developed in a primary hospital.
What was done?
A coordinated protocol was established for the prescription, validation, dispensing, and administration of CAB/RPV IM, involving hospital pharmacy, nursing, and medical teams. Outcomes were assessed after one year of implementation.
How was it done?
A retrospective, cross-sectional descriptive study was conducted, analyzing CAB/RPV IM administrations recorded since March 2024. Inclusion criteria included virologic suppression, stable oral regimen, absence of resistance mutations to CAB/RPV, no hepatitis B coinfection, and patient commitment to scheduled visits. Electronic prescribing via Farmatools® triggered appointments with pharmacy and nursing. Pharmacists provided individualized care and scheduled doses within the ±7-day window, aligned with nursing availability. Patients received automated email reminders; missed appointments prompted follow-up calls. Delays beyond seven days were reported to the physician. Data on administration dates, discontinuations and reasons, viral load, and dosing intervals were extracted from the External Patient Module PRISMA and electronic health records.
What has been achieved?
A total of 518 doses were administered to 138 patients. Nine patients (6.5%) discontinued treatment due to adverse effects, personal/work conflicts, pregnancy, anticoagulation, or lack of appropriate needles. No virologic failures occurred. All doses were administered within the ±7-day window (mean deviation: -1.9 ± 2.0 days). The average number of doses per patient was 3.6 (range: 1–7). Nursing intervened in 4.5% of follow-up visits due to missed appointments. Email reminders reached 81.9% of patients. The protocol enabled integrated care, improved adherence, and ensured safe delivery of CAB/RPV IM therapy.
What next?
Expansion of the protocol to new candidates is planned, along with enhanced interprofessional coordination and digital tools for active follow-up. This experience may serve as a model for other centers implementing CAB/RPV IM in HIV care.
DESIGN AND IMPLEMENTATION OF A PROGRAM FOR THE ADMINISTRATION AND FOLLOW-UP OF PHARMACOTHERAPEUTIC DRUGS IN PATIENTS WITH LONG-ACTING ANTI-HIV DRUGS
Pdf
European Statement
Clinical Pharmacy Services
Author(s)
MARTÍNEZ LLIBERATO, A; COMPANY ALBIR, MJ; VICENTE ESCRIG, E; VALLEJO GARCÍA, R; RUBIO ORTOLÁ, L; GARCÍA MONTAÑÉS, S; BELLÉS MEDALL, MD; FERRANDO PIQUERES, R
Why was it done?
It was carried out to ensure the best monitoring, traceability and conservation of long-acting antiretroviral drugs, as well as to improve adherence and patient quality of life and reduce stigma in HIV patients.
What was done?
A program was developed for the administration and pharmacotherapeutic monitoring of patients who are candidates for long-acting antiretroviral treatment (LA-ART), coordinated with the infectious diseases unit (IDU) and the Hospital Pharmacy Outpatient Unit (HPOU).
How was it done?
After the inclusion of the drugs in the pharmacotherapeutic guide, the following program was designed:
1. Identification and communication to the HPOU by the IDU of patients who are candidates for LA-ART and electronic prescription.
2. Initial visit (week 0):
• Review and validation of the treatment by the pharmacist: indication, dosage regimen, interactions, contraindications.
• Planning of the annual administration calendar, providing two dates within the window period allowed by these drugs. Patients are scheduled for pharmaceutical care (PC) and administration on working Thursdays, in the HPOU Health Education Consultation agenda, which has a nurse.
• Information to the patient by the pharmacist, orally and in writing, about administration and adverse reactions. In addition, the annual appointment schedule is provided.
• Appointment of the patient for the first successive visit, if the patient accepts the start.
3. SMS sent the day before, to remind the patient of the follow-up visit. If the patient cannot attend the scheduled appointment, he/she will contact the HPOU to schedule an alternative date according to the calendar.
4. Successive visits (week 4 and every 8 weeks):
• PC
• Intramuscular administration by a nurse.
In all visits, the information is recorded in the patient’s computerized medical history.
What has been achieved?
Of 18 candidate patients in 18 months, 15 accepted ART after the initial visit. 89 PC and administration consultations have been carried out. Adherence was 100%, all reported local discomfort at the injection site between 1 and 7 days after administration and only 1 patient reported pyrexia.
What next?
A program applicable to all HPOU that have nursing and a Health Education consultation to implement adherence in these patients.