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CHEMOTHERAPY MEETS HERBAL MEDICINE: NAVIGATING THE INTERACTION MAZE IN THORACIC ONCOLOGY

European Statement

Clinical Pharmacy Services

Author(s)

Margot DESCHAMPS, Nejib BORGAAOUI, Jimmy ROSE, Jennifer LE GRAND, Louise NICOLAS

Why was it done?

One of the clinical pharmacy activities in the thoracic oncology department is the analysis the interactions between chemotherapy and Complementary and Alternative Medicine (CAM). Cancer patients often seek alternative treatments which requires a rigorous evaluation of potential interactions. The goal of this study is to assess the methods used to analyze these interactions.

What was done?

To ensure traceability of the analysis, a tracking table for requests was created. The requests, coming from doctors, nurses, or patients, are recorded with key information such as name, date of birth, and the purpose of the analysis. Five information sources were selected, including the Herbal Medicine section of MedlinePlus, the website of the Memorial Sloan Kettering Cancer Center (MSKCC), a database of plants and dietary supplements published by the French National Agency for Food, Environmental and Occupational Health Safety, a database from the European Scientific Cooperative on Phytotherapy, and a publication from the journal Medical Oncology (Vol 36, number 45, 2019).

How was it done?

In nine months, 25 interaction requests were processed, 70% of which were from doctors. The analysis took an average of 30 minutes and were completed within 24 to 48 hours. The interactions mainly concerned oral chemotherapies (n=18), particularly Osimertinib (n=13). The requests involved various CAM (essential oils, medicinal plants, dietary supplements), with an average of four products per request. Desmodium was the most frequently analyzed product (n=5). In total, for 24 CAM, including Desmodium, was not recommended for use after analysis due the drug interaction risk and modification of liver metabolism of chemotherapies.

What has been achieved?

It is difficult to prohibit CAM to patients, and most substances can be taken at recommended doses. However, determining the precise dosage at which an interaction with chemotherapy occurs is complex due to the lack of a single reference. Using various sources allows for cross-referencing expertise and obtaining complementary information. For instance, MedlinePlus offers a generalist approach, while MSKCC focuses on interactions in oncology. Using international sources broadens the analysis and fills geographical or cultural gaps.

What next?

For the future, we would like to develop a tool that compiles the five data sources in order to be exhaustive in our future analysis.

Can my medicine be returned to the refrigerator? Minimisation of wastage in case of storage incidents of cold-chain homecare medications

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European Statement

Clinical Pharmacy Services

Author(s)

Hilde Omestad, Maria Grønkjær Abrahamsen, Fatima Afif Mouaanaki, Charlotte Mosbæk Dybdahl, Anne Wulff Petersen, Emil Dalsgaard Züricho, Philip Hojrizi, Charlotte Arp Sørensen

Why was it done?

The sustainability strategy of the Central Denmark Region include less consumption and less waste. Our Pharmacy delivers an increasing amount of high-cost homecare medications, requiring refrigerator storage. In case of an accidental temperature exposure, patients may ask whether their medicine can be used or not. There may be a delay during transport or a breakdown of their refrigerator at home. During these medicines’ shelf-lives, most products can be kept at room temperature for days, weeks or months. When SmPC and the insert package leaflet says that the product should not be returned to the refrigerator, high-cost medicines sometimes are wasted, only because of this warning, instead of giving them a shorter shelf-life. When we hesitate to return packages to the refrigerator, time can elapse while waiting for the manufacturer’s or pharmacist’s answers to the patient’s questions after storage incidents.

What was done?

The Hospital Pharmacy categorized 47 Blood Coagulation Factors and Monoclonal Antibody Products requiring storage at 2-8 °C if Summary of Product Characteristics (SmPC) had any warning of returning a product to the refrigerator or not, after an unwanted time at room temperature

How was it done?

We asked manufacturers if a return of their product to the refrigerator would cause any harm. Should their product be disposed of because it has been put back into a refrigerator after being left out? Our findings were documented in a local guideline and in the Danish national information database (SAID).
Drug Information Pharmacists discussed several cases of real-world handling situations to be more confident to reduce medicine wastage.

What has been achieved?

Being aware of the reasons for these warnings, reduced medicine wastage in certain cases of incidental storage. The pharmacists have been given tools for pharmaceutical professional assessments in cases of temperature challenges.

What next?

Spread the good news. Improve communication between manufacturer and pharmacy, because manufacturer can’t be responsible for storage different from their SmPC. Inspire manufacturers to improve their storage warnings in SmPC

Impact of drug-drug interaction alerts on prescribing patterns in a teaching hospital

European Statement

Patient Safety and Quality Assurance

Author(s)

Joana Pinto, José Feio, Sebastião Silva, Francisco Machado, Ana Dinis, Margarida Abreu, João Peres, Mariana Guia

Why was it done?

Clinical decision support systems comprising information on DDI improve DDI risk detection, avoiding preventable patient harm. The resulting DDI alerts can change prescribers’ behaviour to benefit patient care. However, an excessive number of alerts can lead to alerts’ desensitisation by prescribers.

What was done?

We monitored the drug-drug interactions (DDI) alerts displayed in the prescription system through three subsequent homologous periods, occurring after the integration of a DDI database in the prescribing software system of a teaching hospital to assess its impact on the prescribing pattern.

How was it done?

We developed a DDI database – MedH® – to be integrated into the prescribing software system to support hard stop DDI alerts. only the higher clinical risk DDIs were included in this database in order to restrain the burden of alerts and warrant acceptance by health professionals.
Data of all inpatient hospital prescriptions over a 12-month period prior to MedH® implementation were extracted and intersected with MedH® DDI BD to identify the top 10 co-prescribed binomials at risk of severe DDI. The number of alerts for the same binomials was then monitored through three subsequent, post-implementation, homologous periods.

What has been achieved?

Considered the TOP10 observed in the pre-implementation period, the number of alerts for all binomials has consistently reduced over the three post-implementation periods analysed.
The integration of MedH® DDI BD into the prescribing system, resulted in changes in the prescribing pattern, translated by a decrease, between 67% and 100%, in the number of alerts for a sample of control risk binomials coinciding with the top 10 co-prescribed risk binomials observed in the pre-implementation period. These results reflect the good acceptance by the professionals and the didactic effect achieved by the exposure to alerts.
More importantly, these results are indicative of the effectiveness of the implementation of MedH® Alerts in reducing patient exposure to high-risk combinations of medicines, thus promoting patient safety.

What next?

It will be important to ensure that data from IDD alerts are rigorously analysed to recognise clinical situations in which the co-administration of risk binomials is justified, to ensure consistent application of recommended risk minimisation measures, and the availability of safer therapeutic alternatives whenever possible.

Software tool development for reconstitution and administration of parenteral antibiotics in hospitals: an international project

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European Statement

Patient Safety and Quality Assurance

Author(s)

Zora Ćetković, Dragana Rajinac, Ivana Baralić , Jelena Marković, Darija Kuruc Poje, Miroslav Kota, Špela Urh, Irina Tegelj, Vesna Bizjak, Dragana Mitrić, Tijana Kovačević, Andrej Pečet, Irena Radivojša, Sanja Filkova, Vesna Bašić-Milošević

Why was it done?

Medication errors regarding reconstitution and administration of parenteral antibiotics are frequent in hospitals. In our study conducted in 12 Southeastern European hospitals in 2021, we demonstrated the need of parenteral antibiotic reconstitution/dilution database in hospital pharmacy practice. Moreover, according to European Statements of Hospital Pharmacy (statement 5.5.), implementation of electronic decision support system by HPs should help to decrease the risk of medication errors. The purpose of software tools is to gather all relevant information regarding parenteral antibiotic reconstitution/dilution and make them easily accessible.

What was done?

A group of hospital pharmacists (HPs) from 6 Southeastern European countries created new software tools (a mobile-responsive website and mobile applications for Android and iOS) for providing information on reconstitution and administration of parenteral antibiotics in collaboration with software developer. These tools contain parenteral antibiotic reconstitution/dilution database in seven different languages (English, Serbian, Croatian, Slovenian, Bosnian, Macedonian and Montenegrin).

How was it done?

Technical requirements for website and mobile applications were designed by HPs. The development of these software tools was carried out by a software developer and funded by European Association of Hospital Pharmacists (EAHP). The final version of the software went through a rigorous evaluation, conducted by HPs during development and all technical problems were resolved consequently.

What has been achieved?

· Designing and developing these software tools helps HPs to provide evidence-based information about parenteral antibiotic reconstitution/dilution at the point of care, thus improving decision-making process and patient safety. · Reconstitution of parenteral antibiotics in wards is efficient and smooth. · Oral and written instructions for parenteral antibiotic reconstitution/dilution are replaced by electronic decision support tools, designed to prevent medication errors. · HP’s interventions are required to support the use of these software tools.

What next?

Our next challenge is wider use of these software tools in order to ensure the appropriate reconstitution/dilution of parenteral antibiotics in wards by nurses and physicians. These software tools are applicable in hospital setting and can be used by all regional hospitals. Additionally, they can be easily incorporated in hospital information system. We also plan to update periodically antibiotic reconstitution/dilution database, as new information becomes available.

Elaboration of a Good Practice Guide for the administration of parenteral antibiotics at children’s hospital

European Statement

Patient Safety and Quality Assurance

Author(s)

MOHAMMED ADNANE EL WARTITI, WAFAA ENNEFFAH, BOUCHRA MEDDAH, MUSTAPHA BOUATIA

Why was it done?

The GPG was developed in a concern of practices standardization to guarantee the safety and efficacy of parenteral antibiotics, especially those stored in vials which reuse in possible only if conditions of administration and stability are respected.

What was done?

We developed a Good Practice Guide (GPG) for the usage of major available parenteral antibiotics.

How was it done?

After we listed all parenteral antibiotics available at the hospital pharmacy, we selected the most used ones and we synthesized all manufacturers’ data to establish a GPG for their administration. We also used literature data to complete missing information in “Summaries of Product Characteristics” related to pediatric use of these drugs. Finally we determined the most antibiotics consuming units according to their defined daily doses, where GPG recommendations will be implemented, before their extension to all other units.

What has been achieved?

The GPG concerned the most used antibiotics, which mainly belong to the following classes: Beta-lactam, Glycopeptide and Imidazole antibiotics, Aminoglycosides and Quinolones. It specifies the galenical presentation, used solvents, volume and duration of administration, stability after reconstitution as well as incompatibilities and special measures relating to the use of these drugs. The most antibiotics consuming units are pediatric intensive care units, “IIB” pediatric unit and pediatric surgical emergency department.

What next?

The approach used in this work can be adopted in other similar structures in order to establish GPGs within the framework of a quality control policy aiming to raise the standard of care.

ANALYSIS OF DISCREPANCIES BETWEEN DATABASES OF DRUG-PLANT INTERACTIONS: A NEW TOOL THAT FACILITATES DAILY DECISION MAKING

European Statement

Clinical Pharmacy Services

Author(s)

Belén Serna Serrano, Victoria Lerma Gaude, Ana Valladolid Walsh, Cristina Del Pozo Carlavilla, Juan Manuel Collado Sanz, Héctor Alabort Ayllón, Eduardo Tébar Martínez, Andrea Drozdz Vergara

Why was it done?

In the pharmacist-patient clinical interview (CI), DP-I revision is frequent due to consumption increase of phytotherapy in recent years. The aim of the initiative was to study the degree of discrepancy (DD) based on the severity criteria (SC) found about the recommendations on the management of DP-I. Nowadays there are multiple databases with lack of unification. Patients diagnosed of Multiple Sclerosis (MS) are frequently interviewed by the pharmacist and they often take herbal medicines (HM).

What was done?

We unified the information collected from the commonly consulted databases of drug-plant interactions (DP-I) whose information could be scarce or contradictory, by creating a tool based on the most consulted plants in our clinical practice (CP).

How was it done?

To create our own DP-I tool, the sources consulted were:
– Our own plant database based on CP. A total of 56 plants.
– Six official databases of DP-I: (A)-Phytotherapy official monographs, (B)-MedInteract®, (C)-Micromedex®, (D)-UpToDate-Lexicomp® (E)-Medscape®.

In order to unify the DP-I information consulted and to be able to identify the DD (0 to 2), the SC for all databases were unified in 3 levels: if the database had 5 levels (1=1-2; 2=3-4; 3=5) or 4 levels (1=1-2; 2=3; 3=4). In first place we decided to test this tool with a small sample size of drugs (6 drugs commonly used for the treatment of MS) to check whether the discrepancy between the databases usually consulted was significant or not.

What has been achieved?

Finally, 6 DP-I were detected with Hypericum perforatum (HP) and Echinacea angustifolia (EA):

The DD seems to be similar between A-B databases and greater respect to the rest of them. Depending on the database consulted the pharmacist’s performance could change and consequently, pharmaceutical care may be affected. Since this tool was implemented in our CP, none of our MS patients have taken HP or EA, therefore, it has not been necessary to modify their treatment because of DP-I.

What next?

This tool could speed up the pharmacological review of possible DP-I and improve decision-making for the care of MS patients. Our next step is to increase the sample of analysed drugs commonly used in other pathologies, such as antiretroviral drugs.

Horizon Scanning in Denmark: Providing the health care system with an overview and impact estimation of new medicines

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European Statement

Selection, Procurement and Distribution

Author(s)

Helle Brauner

Why was it done?

There was a need for improved planning and preparing processes, as when it comes to price negotiations and estimates on financial burden and strategic procurement.

What was done?

Amgros, a part of the Danish health care system, has secured the supply of medicines and hearing aids to public hospitals and hearing clinics across Denmark for 30 years. This is done through efficient procurement and tendering procedures, creating economies of scale and savings.

In addition to this, in January 2017, Amgros launched its own Horizon Scanning unit. Now, the Danish Horizon Scanning system provides the health care system with an overview of medicines, indications and extensions e.g. pharmaceutical forms expected to be entering the Danish market within the next 2-3 years.

How was it done?

In 2016, it was decided to establish an Horizon Scanning system in Denmark. Then, input from internal and external stakerholders regarding their needs and expectations were gathered.

The outputs from the Horizon scanning unit consist of an overview of medicines about to reach the Danish market, as well as estimates of costs for new, expensive medicines and possible savings, for example if there are cheaper biosimilar drugs on the market. We also assess potential patient population and location of treatment. This is done in close cooperation with several Danish clinicians.

Sources for verifying and validating the data inputs are primarily EMA, complemented with commercial databases and a niche group of other sources. Data is gathered in a database.

What has been achieved?

The outputs enable our stakeholders to better plan the introduction of new medicines, to secure more cost-effective health solutions for everyone and to achieve more health for money in the Danish hospital setting.

Danish Regions, the interest organization for the health care regions, use the estimates in their annual negotiations with the Government on finances and the individual regions use them in their own budgets.

The predictability this system brings to Denmark is key in a future with more rare diseases, treatments and advanced pricing.

What next?

The Horizon scanning function is continuously being developed to meet the needs of our stakeholders, as we want to enable them in providing health care to the Danish citizens.

IMPACT OF PLANTS ON ANTICANCER DRUGS METABOLISM: DEVELOPMENT OF A DATABASE TO FACILITATE THE PHARMACIST’S EXPERTISE (submitted in 2019)

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European Statement

Clinical Pharmacy Services

Author(s)

ANAIS AMAR, SIMON CLAUTRIER, MORGANE GIOVANELLI, REGINE CHEVRIER

Why was it done?

The phytotherapy market has continued to grow for several years. However, in oncology, concomitant use of plants with oral or injectable chemotherapies can be harmful. Plants can interact with many cytochromes (CYP), impacting on the biotransformation and kinetics of drugs. While grapefruit or St John’s wort are already recognised as interfering with many therapies, the impact of many plants remains unknown for healthcare professionals. Tools exist to evaluate their effects on drug metabolism, but the multiplication of sources delays and complicates the advice of pharmacists.

What was done?

Centralise information on plant metabolism on a single support by creating a database. Facilitate pharmacist’s expertise about interactions between plants and anticancer drugs.

How was it done?

To create the database, it was necessary to establish an exhaustive list of plants. Three sources of information have been used:
– Inventory of phytotherapy products marketed in 4 drugstores
– Census of plants consumed by patients seen in pharmaceutical consultation (PC)
– Consultation of websites specialized in phytotherapy
Then, an Excel table has been developed:
– each line corresponds to a plant
– each column corresponds respectively to 17 CYP, a transport protein (Pgp), estrogen-like (EL) and antioxidant (AO) properties of the plant.
A colour code has been defined according to the inhibitory (yellow), inductive (blue), EL (purple) and AO (red) action of the plant. If there is no interaction, the box remains blank.
Plant effects data were collected from Hedrine®, Oncolien®, MSKCC, RX list and Drugs.com websites.

What has been achieved?

Finally, 174 plants have been accounted in drugstores, 82 were identified during PC and 129 found on websites. If 10% of plants have an EL action and 16% an AO effect, approximately 30% have inductive and/or inhibitory action of at least one CYP and/or PgP. Since the tool’s creation: 91% of answers could be given immediately to patients compared to only 9% delayed (plants still unreferenced).

What next?

This database is an essential tool for answering questions from patients with anticancer drugs. It saves precious time and responsiveness during PC, but also during patient phone calls. However, critical work with divergent information between sources is to be expected. Currently, as a precaution, we don’t recommend the use of plants subject to such a contradiction.

SAFETY IMPROVEMENT IN PAEDIATRICS: ASSISTED PRESCRIPTION OF INTRAVENOUS MIXTURES (submitted in 2019)

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European Statement

Patient Safety and Quality Assurance

Author(s)

Iván Maray Mateos, Miguel Alaguero Calero, Adrián Rodriguez Ferreras, Cristina Calzón Blanco, Cristina Álvarez Asteinza, Lucía Velasco Roces, Ana Lozano Blazquez

Why was it done?

Intravenous drugs in the paediatric population bring up additional issues than the usual in adults. In their prescription, not only does the dose have to be adapted to the patient’s weight, the volume in which the drug is diluted must also be adapted to the reduced fluids requirement without jeopardising the stability of the mixture. In view of these facts, IV drug prescription in paediatrics implies a higher risk of medication errors. This new prescribing system simplifies prescription and reduces risks.

What was done?

Development of an assisted prescription system of intravenous mixtures adapted to paediatric patients in which both the drug dose and the diluent volume are automatically calculated according to the patient’s weight.

How was it done?

A literature review of drug dosing in paediatrics and their stability in different diluents was performed. For every drug the following parameters were considered: maximum dose in children (mg/kg), maximum concentration allowed (mg/ml), common doses and volumes in adults. Using these values, a system was built which calculated drug dose and diluent volume according to the patient’s weight and the maximum concentration allowed for stability reasons. For safety and to ease the preparation, the diluent volume in millilitres was rounded up to the next 10. In order to avoid overdosing overweight or older paediatric patients, maximum dose and diluent volume were narrowed down to the usual quantities in adults. Ultimately, this system was integrated in the electronic prescription system. A protocol was created, named “drug name” IV mixture PEDIATRICS. So, by selecting this protocol in a specific patient, the target dose and the diluent volume are automatically calculated.

What has been achieved?

This system was implemented for 38 drugs. From July 2018 to April 2019, 910 IV mixtures have been prescribed from the following Anatomical Therapeutic Chemical (ATC) groups: A02 Drugs for acid related disorders (39), J01 Antibacterials for systemic use (287), J02 Antimycotics for systemic use (3), J05 Antivirals for systemic use (8), A04 Antiemetics and antinauseants (175), N02 Analgesics (395), N03 Antiepileptics (3).

What next?

This method could be implemented in other electronic prescription programmes. The system must be updated by the Pharmacy Department, introducing new drugs and constantly reviewing stability databases, posology regimens, and information regarding dilution of parenteral drugs.

SUCCESSFUL DEVELOPMENT OF A SHARED INFORMATION DATABASE FOR HOSPITAL PHARMACIES IN DENMARK – BENEFITING FROM AGILE PROJECT MANAGEMENT (submitted in 2019)

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European Statement

Clinical Pharmacy Services

Author(s)

Stine Ulsø, Hilde Omestad, Susanne Weng Rømer, Sisse Emilie Mejsner, Mads Nielsen, Jesper Heltoft-Christensen

Why was it done?

The existing solution, established in 2001, was running on an insecure platform, the system was expensive to maintain and changes difficult and slow to implement. The need for an update led to a change of supplier, hosting and platform.

What was done?

A new database was developed for documentation and quality assurance of drug related queries received by hospital pharmacies in Denmark. The information in the database is shared across all hospital pharmacies in Denmark and is an important tool for the Medicines Information Centers located there. Existing queries were transferred from the old to the new database.

How was it done?

A working group was established consisting of three pharmacists and superusers from three different hospital pharmacies, one project manager employed by the sponsor (Amgros) and two developers employed by the new supplier (Progressive). The project was structured using monthly physical meetings and ad hoc video conference meetings. The work tasks in the development process were divided and carried out in two-week sprints by the developers and subsequently tested and validated by the pharmacists. All participants agreed to a periodic heavy workload and showed great flexibility. The close and frequent collaboration between all members affected the teamwork in a positive way, hence the group was motivated and managed to agree on common solutions and compromises despite different database usage and different locations.

What has been achieved?

A new, stable and more intuitive database was developed in only 5 months due to the structured and flexible way of working and a close motivated teamwork. The database was taken into use from one day to another and quickly adapted. Since the development several hospital pharmacies have increased their use of the database. The amount of information shared nationally has improved.

What next?

The initiative resulted in a useful tool implemented within a short time. The way of working intensively and focused with physical meetings and video conferences made a good basis to succeed. Especially the sprint cycles can be used in different healthcare settings involving different projects.

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