GPI: DEFINING DOSAGE REGIMENS OF ERLOTINIB AND GEFITINIB IN NON-SMALL CELL LUNG CANCER PATIENTS USING MODELLING AND SIMULATION

DEFINING DOSAGE REGIMENS OF ERLOTINIB AND GEFITINIB IN NON-SMALL CELL LUNG CANCER PATIENTS USING MODELLING AND SIMULATION

 

European Statement: 

  • Clinical Pharmacy Services 

Author(s): 

SOFIA KONSTANTINIDOU
VANGELIS KARALIS 

What was done?: 

Population pharmacokinetic (PK) – pharmacodynamic (PD) modelling was utilised to simulate erlotinib and gefitinib dosage regimens for non-small cell lung cancer. In silico clinical trials with virtual patients, of several resistance levels, were simulated in order to optimise pharmacotherapy and get better therapeutic outcomes.

Why was it done?: 

Tyrosine kinase inhibitors (TKIs), like erlotinib and gefitinib, are widely used in anticancer therapy. However, after long term administration of TKIs, resistance is observed in the majority of patients. Thus, it is necessary to be able to define individualised dosage regimens for TKIs in cancer patients. Nowadays, modelling and simulation approaches represent the most powerful tool in the hands of clinical pharmacists towards precision medicine.

How was it done?: 

The utilised PK/PD model and average parameter values were obtained from the study of Eigenmann and colleagues. This model was fully validated using statistical criteria and goodness of fit plots. In order to simulate many possible conditions that may occur in clinical practice, several different values of erlotinib and gefitinib clearance, absorption rate, pharmacodynamic characteristics (like tumor volume), and resistance were assessed. In addition, several dosage schemes were simulated. The entire modelling work was performed in Monolix® 2019R1.

What has been achieved?: 

Concentration vs. time and effect vs. time plots for the virtual patients were simulated for a variety of conditions and tumour resistance levels. For both TKIs, decrease of body clearance led to higher plasma concentrations, as well as more intense and longer duration of the effect (i.e. tumour volume shrinkage). Enhanced drug effect on resistant cells resulted in a decrease in tumour volume. In addition, a variety of concentration-time profiles were simulated, making it possible to choose the best regimen for each patient.

What next?: 

In this study, the use of modelling techniques led to the simulation of many conditions of patients and adjustment of dosage regimens according to their needs. Wider application of in silico methods using virtual patients will allow the design of the most appropriate individualised dosage schemes tailored to the patients’ requirements.

Keywords: 

  • Clinical pharmacy›Clinical pharmacy services
  • Drug prescribing and dosing›Optimisation of therapy
  • Drug safety›Safety profile
Conflict of interest: 

I have no potential conflict of interest to disclose

PROMOTING THE USE OF SAFER INJECTABLE MEDICINES USING A NOVEL METRIC

Author(s): 

Gillian Cavell

What was done?: 

We have developed a series of metrics to measure compliance with national guidance for the safe use of injectable medicines. The guidance recommends use of ready-to-use (RTU) or ready-to-administer (RTA) injectable products, where these are available, to reduce the risk of patient harm from errors in the preparation of injections and infusions on hospital wards.

Why was it done?: 

Despite the availability of RTU and RTA formulations of high-risk injectable medicines they were not always used. We developed the metric, to compare the use of RTU and RTA injectable medicines with the use of concentrates requiring further dilution or manipulation prior to administration e.g. dilution of morphine 10 mg/ml to 10 mg/10 ml prior to intravenous administration, e.g. withdrawal of 5 x 10 ml fentanyl 500 mcg/10 ml into a 50 ml syringe for continuous infusion, and identify areas for improvement.

How was it done?: 

The metric utilises pharmacy-issue data to compare the number of units of RTU or RTA formulations issued to wards and clinical areas with the numbers of units of alternative products of the same drug entity. Expressed as a percentage the metric informs the organisation of the extent to which safer injectable medicines are being used, providing a baseline against which to review practice and reinforce the need to use alternative, safer formulations. A high percentage indicates good compliance.

What has been achieved?: 

The metrics have been used to successfully maximise the use of a range of safer formulations including RTA potassium chloride, RTU fentanyl 2500 mcg/50 ml vials for critical care infusion, 100 mg/10 ml paracetamol in neonatal units and RTU magnesium sulphate 20% (50 ml vials) for obstetric emergencies. Since the introduction of the metrics in 2016 a monthly scorecard of performance is reviewed by the Hospital Medication Safety Committee to identify and account for deviations.

What next?: 

The metrics are being shared with other organisations to benchmark performance. Ideas to promote implementation and business cases can be shared between organisations who may find implementing RTA and RTU injectable medicines challenging, especially where these are more expensive than formulations in established use.

Keywords: 

  • Drug administration›Ready to use
  • Hospital setting›Secondary care
  • Patient safety›Error-avoiding strategies
Conflict of interest: 

I have potential conflict of interest to disclose *

Disclosure statement: 

I have received an honorarium from hameln pharmaceuticals to present a case for using ready-to-use fentanyl 2500mcg/50ml infusions in critical care units. hameln are currently the only licensed manufacturer of this product.

IMPLEMENTING THE PRODUCTION OF STERILISED SYRINGES IN THE HOSPITAL: IMPROVING MEDICATION SAFETY AND SAVING HEALTHCARE COSTS

Author(s): 

Karin Larmene-Beld
Rommert Wijnsma
Gerrit de Weerd
Maarten Postma
Erik Frijlink
Katja Taxis

What was done?: 

Development and implementation of sterilisable plastic syringes produced in the hospital pharmacy for large-scale production of ready-to-administer products.

Why was it done?: 

Medication administration errors are common in hospital practice. Meta-analyses suggest that about 10% of administrations are erroneous, with much higher error rates occurring during intravenous drug administrations. It has been demonstrated that 21% of the errors can be eliminated when prepared syringes are used. Many countries struggle with the problem of optimising the process of safe parenteral medication in hospitals. Different guidelines across countries outline how preparation of parenteral medication in the clinical environment should be done. Recently the Council of Europe published a resolution about preparation of medication which encourage the supply of ready-to-administer products by the pharmacy. Moving the activities of preparation of medication from the clinical environment to the pharmacy requires investments in pharmacy equipment but will result in efficacy, better quality and reduction in preparation medication errors in the hospital.

How was it done?: 

A new development in this area are ready-to-administer pre-filled sterilised syringes (PFSS) produced by the pharmacy. PFSS are produced on stock under GMP conditions by the hospital pharmacy using (semi) automatic filling and closing machines whereby quality and safety are embedded in the whole process of manufacturing. A total cost of ownership analysis is performed showing PFSS prepared in the hospital pharmacy yielded cost savings compared to conventional preparation on the ward. The process of production, filling, closing and sterilisation has been validated using newly acquired equipment. With the introduction of the cyclic olefin polymer (COP) syringes a new type of primary container is implemented in the pharmacy. To ensure patient safety and product quality a science- and risk-based strategy has been developed for testing extractables and leachables to qualify the new container as primary packaging material.

What has been achieved?: 

Introducing PFSS is cost saving for the healthcare system:– COP syringes are suitable as primary packaging material; –enhancement styles for better readability of labels are established; and – already, 15 products are validated and available for use in the hospital. 1. KHM Larmené-Beld KHM, Touwen-Spronk J, Luttjeboer J, et al. A cost minimization analysis of ready-to-administer pre-filled sterilized syringes in a Dutch hospital.. Submitted for publication in Clinical Therapeutics. 2. Larmené-Beld K, Kuiper A, van Berkel S, et al. A science- and risk-based strategy to qualify sterilized prefilled syringes as primary packaging material in a hospital pharmacy. Abstract submitted for 24th EAHP Congress. 3. Larmené-Beld KHM, Kim Alting E, Taxis K. A systematic literature review on strategies to avoid look-alike errors of labels. Eur J Clin Pharmacol 2018 74:985–93.

What next?: 

Introducing more drugs as ready-to-administer products. Optimising the label of ready-to-administer syringes to avoid look-alike errors based on the results of the review.

Keywords: 

  • Patient safety›Error-avoiding strategies
  • Patient safety›High risk medication
  • Preparation and compounding›Sterile production
Conflict of interest: 

I have no potential conflict of interest to disclo

PROTOCOL IMPLEMENTATION FOR PRESCRIBING AND DISPENSING POSTEXPOSURE PROPHYLAXIS KITS FOR HUMAN IMMUNODEFICIENCY VIRUS IN A THIRD-LEVEL HOSPITAL

Author(s): 

Clara Estaún-Martínez
Isabel Moya-Carmona
Laila Dani-Ben Abdel-lah
Jose Manuel Fernández-Ovies

What was done?: 

A protocol was implemented in order to standardise the prescription and dispensation of postexposure prophylaxis (PEP) after occupational or nonoccupational exposure to human immunodeficiency virus (HIV).

Why was it done?: 

This initiative was taken in order to improve uptake and completion rates of PEP, and to homogenise the healthcare circuit for these patients and the prescribed drugs.

How was it done?: 

A multidisciplinary team including Infectious Diseases and Preventive Medicine (PM) doctors, pharmacists and Emergency Room (ER) staff developed the following protocol for PEP according to World Health Organisation and national guidelines: – standard three-drug regimen for PEP: Tenofovir disoproxil fumarate/Emtricitabine + Raltegravir for 28 days. The pharmacy service (PS) repackages kits for five, 23 or 28 days that include antiretroviral drugs (AD) and written information about the treatment (use, length of the treatment, main interactions and side effects, contact number). Only 5-day PEP kits will be located in the ER. – Twenty-four-hour access granted to PEP kits as it is strongly recommended to initiate PEP as early as possible (ideally within 72h). – Established healthcare circuit for patients in the ER: • Monday–Fridays (8h00–15h00): patients will be immediately referred to PM, then they will go the PS in order to receive a 28-day PEP kit and pharmaceutical care. • Out of this schedule and bank holidays: ER doctors will give patients a 5-day PEP kit and they will be referred to PM the next working day. After visiting PM, the patient will go to the PS in order to receive the rest of PEP (23-day kit) and pharmaceutical care. – Several meetings took place in order to explain this new circuit to the health professionals involved and written copies were available on the ER as well as on the intranet.

What has been achieved?: 

The implementation of this protocol was well embraced by all the staff involved, since it allowed a more efficient healthcare circuit for the patients. It also optimises the evaluation and monitoring of these patients by PM and the pharmacist, and grants prompt PEP initiation and 24h access to the AD. The 28 days (or 5+23 days) kits help to accomplish the proper length of treatment, without using the regular packages which include 30 days of treatment (saving €43.17 per treatment).

What next?: 

We will monitor the compliance with this protocol and the drugs prescribed for PEP.

Keywords: 

  • Drug prescribing and dosing›Prescription compliance
  • Quality›Improvement action
  • Theraputic areas›Antiretroviral therapy
Conflict of interest: 

I have no potential conflict of interest to disclose

HOSPITAL PHARMACY UNIFIES ELECTRONIC STANDARD PRESCRIPTION THROUGHOUT THE REGION

Author(s): 

Linda Jeffery

What was done?: 

The regional Drug and Therapeutics Committee (DTC) commissioned the Hospital Pharmacy, Central Denmark Region to take over management of electronic standard prescriptions (ESP) in the shared Electronic Prescribing System (EPS). The pharmacy was also commissioned to lead the unification of local to regional ESPs, in collaboration with clinical specialists. ESPs are electronic ‘packages’ of one or more prescriptions, set up for treatment of defined conditions/procedures e.g. knee-replacement. When the clinician prescribes an ESP, the predefined prescriptions appear automatically in the patient’s medicines list.

Why was it done?: 

The primary aim was to increase patient safety by quality-assuring ESPs and guiding clinicians to rational and safe prescribing. The Central Denmark Region (1.3 million citizens) has five hospitals, each with their own hospital and ward management. ESPs were previously set up and maintained locally, often by clinicians at ward level, resulting in several thousand, and a huge variety of ESPs for the same indication/treatment. Often only small differences separated these, but larger differences were also observed. Both patients and clinicians move around hospitals within the region. Varying ESPs from hospital to hospital confused clinicians and compromised patient safety.

How was it done?: 

The Hospital Pharmacy highlighted clinical areas/treatments with several variations of the same ESP. The DTC appointed relevant clinicians to work with a pharmacist on unifying these, to one (or more) standardised ESPs, to be used in the whole region. The pharmacist was coordinator for the ad-hoc working groups. After approval by the DTC, these ESPs replaced the existing. If a department wanted an ESP that differed from the regional ESP, this had to be approved by the DTC.

What has been achieved?: 

Regional ESPs have been approved for: • Abortion (reduced from 17 to six). • Helicobacter pylori eradication (reduced from 28 to two). • Treatment of paracetamol-overdosage. Many new ESPs have been approved, promoting: • Safe prescribing of complicated regimes e.g. fosphenytoin loading/maintenance. • Use of regional formulary drugs e.g. antibiotics for pneumonia/urosepsis.

What next?: 

We continue to work on other regimes that can be unified e.g. treatment of Wernickes prophylaxis/syndrome and parenteral nutrition. We recently met with pharmacists from two other regions that use the same EPS as us – maybe we can share ESPs nationwide in future.

Keywords: 

  • Drug prescribing and dosing›Computer assisted prescribing (cpoe)
  • IT›Electronic prescribing system
  • Patient safety›Error-avoiding strategies
Conflict of interest: 

I have no potential conflict of interest to disclose

DRUG-FOOD INTERACTION GUIDE PREPARATION FOR OUTPATIENT CONSULTATION

Author(s): 

Gregorio Romero Candel
Paula Ruiz Belda
Carmen Caballero Requejo
Maria Jesus Sanchez Cuenca
Jose Marco del Rio
Juilan Castillo Sanchez
Luna Carratala Herrera

What was done?: 

Preparation of the drug and food interaction guide for outpatient consultations.

Why was it done?: 

Some drugs dispensed in the outpatient office present interactions with food, leading to changes in their bioavailability. These changes which can result in a decrease in therapeutic activity or an increase in adverse effects, when dealing with narrow therapeutic margin drugs, may lead to alterations in their efficacy and/or toxicity. Developing the quick and accessible consultation table, we improved the quality and effectiveness of the treatment.

How was it done?: 

The technical specifications of all drugs that are dispensed in the hospital outpatient office were consulted, and the possible interactions with food of every one of them were analysed by consulting the following electronic databases: Technical sheet, Bot Plus, Micromedex, Pubmed, UpToDate and Online Medicine Information Centre of the AEMPS. A database was developed with drugs that presented some type of restriction with meals, designing a quick reference table for outpatient consultation.

What has been achieved?: 

One-hundred specialities were reviewed, of which 22 were to be taken without food, 43 with food and 35 could be taken with or without food. The information given to the patient was quick and efficient, improving the effectiveness and safety of the treatment.

What next?: 

Our goal is to continue developing tools that allow us to provide quality information to the patient, improving the effectiveness and safety of treatments.

Keywords: 

  • Clinical pharmacy›Medicines optimisation
  • Drug information›Patient information
  • Drug safety›Drug interaction
Conflict of interest: 

I have no potential conflict of interest to disclose

PREPARATION OF A CYTOSTATIC STABILITY GUIDE AFTER RECONSTITUTION AND DILUTION

Author(s): 

Gregorio Romero Candel
Paula Ruiz Belda
Maria del Carmen Caballero Requejo
Maria Jesus Sanchez Cuenca
Jose Marco del Rio 
Julian Castillo Sanchez
Luna Carratala Herrera

What was done?: 

A cytostatic stability guide after reconstitution and dilution has been made. The active principles and commercial presentations that are used in the intravenous mixtures area were reviewed.

Why was it done?: 

In common clinical practice, the stability of medications is an area of interest to obtain maximum security and efficiency. After reconstitution and dilution, knowing the validity period is very important for the effectiveness and safety of the treatment, since it must be administered to the patient under the appropriate conditions. In recent years, a large number of high-impact cytostatic medicines with limited stability data have been registered and incorporated into clinical practice. Frequently, the stability data results are contradictory or insufficient. The main goal is to make a reliable quick guide of reference with the validity periods of the reconstituted and diluted active principles according to physicochemical stability, therefore increasing safety, reducing queries for these doubts and improving the management of unused remains that have high economic impact.

How was it done?: 

The obtaining of the physical-chemical stability data has been done by reviewing the information available in Stabilis, Pubmed, Lexicomp and technical data sheets.

What has been achieved?: 

Fifty-four pharmaceutical specialities from 44 active principles, all in the cytostatic group, were checked. Tables of reference for the elaboration sites were made for consultation. It has reduced the number of consultations conducted and improved the time of preparation of these products. The rest of the elaborations for other administrations have been taken advantage of, making a better use of the pharmacotherapeutic resources.

What next?: 

The next step is to keep developing consultation tools that improve the safety and management of hospital drugs.

Keywords: 

  • Clinical pharmacy›Medication error
  • Drug safety›Drug safety
  • Patient safety›High risk medication
Conflict of interest: 

I have no potential conflict of interest to disclose

A SET OF QUALITY IMPROVEMENT INTERVENTIONS TO INCREASE THE PERCENTAGE OF STAT IV MEDICINES, MEETING THE GOAL OF BEING READY WITHIN 30 MINUTES

Author(s): 

MELINDA LITAO
HANY ELATROUSH 
KHATHLEEN ESER
ARWA AFANA
AHMED BAIBRAHIM
JAYSON DE JUZMAN
BAYAN RAMBO
DERI PASCUAL
MA ENCARNACION DELOS ANGELES
MANAL SALLAM
MALIK KHUWAJA

What was done?: 

A set of quality improvement interventions to increase the percentage of STAT IV medicines, meeting the goal of being ready within 30 minutes.

Why was it done?: 

STAT orders have always been a priority, however there are some areas which require some modification in the workflow to attain higher efficiency and to increase the percentage of STAT IV medicines, meeting the goal of being ready within 30 minutes.

How was it done?: 

This was a pre-post study in a government hospital between January and September 2018. LEAN and FOCUS-PDCA models were implemented to design the process of improvement. A medication-tracking system (MedBoard) was used to collect the data to measure the number of STAT IV medicines ready within 30 minutes. Data was also collected from the number of phone calls and faxes received from the day procedure unit (DPU) and home health care unit (HHC).

What has been achieved?: 

The cumulative data showed an increase in the percentage of STAT IV medicines being ready by 7%, equivalent to 707 orders per month (90% vs 97%), a reduction in the number of phone calls by 87.5% (48 vs six calls per day) and fax by 100% from the DPU and HHC units, which means that implementing the set of interventions were associated with an increase in percentage of STAT IV medicines being ready within 30 minutes. Additionally, there was a significant decrease in the number of phone calls and faxes, which allowed pharmacists to focus more on STAT IV orders.

What next?: 

Since the hospital pharmacy receives numerous orders on a day-to-day basis, this will facilitate prioritisation during the entire process. This aligns with the hospital goal of attaining ‘zero harm’, and is therefore a good example of good practice in a hospital setting. The use of Medboard in tracking medications and monitoring performance can be applied to allow any healthcare setting to ensure that goals are reached, and performance is maintained at the highest level. Designing a list of eligible medications that can be ordered as STAT can be used as a guide to avoid the abuse of STAT orders and can help in prioritising order preparation in the STAT IV room.

Keywords: 

  • Drug administration›Ready to use
  • Drug selection›Drug selection
  • Patient safety›High risk medication
Conflict of interest: 

I have no potential conflict of interest to disclose

PHARMACISTS IMPROVE DOCUMENTATION OF DRUG ALLERGIE

European Statement: 

  • Patient Safety and Quality Assurance 

Author(s): 

Mohammed Almeziny
Fahad Alkharji 
Ali Alkhudair 
Jameel Al Mutairi

What was done?: 

Increase the allergy documentation from 14% to 96%.

Why was it done?: 

Poor allergies’ documentation may cause harm to the patients, if the concerned medication reaches them. The hospital is planning to implement a new Health Information System, which includes a Computerised Provider Order Entry. However, this is a long-term project, so in order to minimise that risk, the hospital administration gave the pharmacists the privilege to do so. The percentage of documented drug allergies was 14%. The issue of compliance from the medical, nursing and pharmacy staff was a major obstacle in allergies’ documentation. For that reason, the pharmaceutical services initiated an improvement project to enhance allergies’ documentation. it is the responsibility of the physician to document any allergy on the inpatient prescription form (IPPF). On the other hand, it is the responsibility of the nurse to ensure that all information is completed on the IPPF before it is sent to the pharmacy. The role of the pharmacist is to document the patient’s allergy in the pharmacy system.

How was it done?: 

The FOCUS PDCA was adopted. Find: It was found that the compliance rate was not satisfactory. Patients might receive a medication that is known to cause an allergic reaction, because the allergy was not documented and communicated with other healthcare providers. Organise: The team consisted of all involved departments. Clarify: Some IPPF may not contain allergies and some pharmacy staff do not document the allergy in the pharmacy system. Understand: The factors that may influence the process were identified, although some healthcare professionals consider the documentation as a time-consuming process. The pharmacy system is an old system which does not support enforcing function. Select: The targeted outcome was 90% within 1 year of its inception, July 2017 to July 2018. Plan: All allergies MUST be assisted, and the pharmacy will act as the enforcing body. Do the plan: All pharmacists were reminded to enforce hospital policies by not accepting any incomplete prescription and document all drug allergies in the pharmacy system. Check: Statistics regarding compliance were presented in monthly meetings to highlight the challenges, difficulty or any serious issue. It is a proactive meeting and members can freely suggest any tools required to improve the situation.

What has been achieved?: 

There was a significant improvement from 14% to 96%.

What next?: 

Start e-prescription to enforce the documentation of allergies.

Keywords: 

  • Drug safety›Allergy
  • Patient safety›Error-avoiding strategies
  • Quality›Risk minimization
Conflict of interest: 

I have no potential conflict of interest to disclose

SAFER DRUGS WITH AWARD-WINNING DATABASE

European Statement: 

  • Patient Safety and Quality Assurance 

Author(s): 

Teimori Kaveh

What was done?: 

Nurses, doctors and pharmacists were provided with accessible and evidence-based information on IV drug compatibility in order to improve drug therapy, working environment and patient safety.

Why was it done?: 

Hospitalised patients often need multiple IV drugs simultaneously which are commonly mixed in-line before entering the bloodstream. Physicochemically incompatible drugs cause reduced efficacy, clogged catheters and drug precipitation, which can be harmful or even fatal. The risks add uncertainty to the stressful working environment for clinical practitioners. According to a local 2012 survey 68% (n=44) of Sahlgrenska University Hospital (SUH) intensive care unit (ICU) nurses had co-administered drugs uncertain of their compatibility. Hospital pharmacists were hence asked for guidance to optimise compatibility and patient safety.

How was it done?: 

Drug compatibility data was collected by hospital pharmacists who assessed its applicability to Swedish conditions. The results were documented in charts and procedure documents. A project for creating a database was initiated in collaboration with the IT organisation in Västra Götaland Region (VGR). A survey was designed to evaluate how the SUH’s ICU nurses experienced the database. Collaboration with nurses, doctors and clinical pharmacists helped to improve the quality of the database.

What has been achieved?: 

Drug compatibility lectures were given to nurses, doctors and pharmacists on a continuous basis. Procedure documents were implemented in eight clinics. A peer-reviewed workflow was established. The database contains over 2,500 assessed drug combinations. Over 700 nurses, doctors and pharmacists from 11 counties plus Norway and Denmark have requested access to the database. Clinics avoid drug mixing by choosing multi-lumen catheters with greater capacity. The 2016 survey showed that 88% (n=86) of SUH’s ICU nurses had co-administered drugs uncertain of their compatibility. The database affected their decisions in 93% (n=45) of the cases, 85% (n=34) found information easier and 88% (n=34) felt more certain when making decisions. A new pharmacist role – IV Compatibility Manager – was introduced and implemented in VGR. In 2016, this work received the national annual award Guldpillret (‘The Golden Pill’).

What next?: 

In the next years, the database will become nationally available and integrated into electronic journal systems. Compatibility issues may then be identified when prescribing, further improving patient safety.