Off-label drug use in neonates and infants in Spain: A five-year observational study.

OBJECTIVES: To provide information about the off-label rate of all drug prescriptions in neonates and infants up to 1 year in Spain. Also, to analyse the off-label prescription of medicines under current practice in this age group according to different evidence sources. STUDY DESIGN: A five-year (2015-2019) exploratory observational study about off-label prescription in neonates and infants (0 to 1 year) at primary health care in Spain. All drug prescriptions in this age group were analysed and classified according to their labelling in off-label or on-label. The drugs prescribed off-label were subsequently reviewed in national formularies and other databases to assess its evidence of use beyond what is recommended in the Summary of Product Characteristics (SmPC). RESULTS: On average 34.50% of total prescriptions were prescribed off-label according to the SmPC. 17.93% of total prescriptions in neonates and infants up to 1 year old were not based on clinical evidence from SmPC, Pediamécum, BNF or DailyMed. In more than 88% of cases, off-label use was related to the posology section of the SmPC, followed by the therapeutic indications and contraindications sections, in 35.20% and 24.10% of cases, respectively. Almost 13% of off-label drugs were over-the-counter. Salbutamol followed by topical tobramycin and colecalciferol were the drugs most prescribed off-label. CONCLUSIONS: Off-label use of drugs remains as an important public health concern, especially for neonates and infants up to 1 year, who receive the greatest proportion of off-label prescriptions. The evidence-based off-label prescription is a widespread practice that has shown a stable trend during the 5-year study period providing also a certain extent of flexibility to paediatricians in some therapeutic decisions.

Effects of the Off-Label Drug Prescription in the Paediatric Population in Spain from the Adoption of the Latest European Regulation: A Pre-Post Study.

The year 2021 marks the 15th anniversary of the Paediatric Regulation (1901/2006/EC) in Europe. The main aim of the study was to conduct a pre-post comparison on the annual off-label prescription rates in the under-18 population in Spain and assess the potential influence of the Paediatric Regulation adoption. An observational study in the paediatric population was performed. Four cross-sectional annual periods, one before and the three latest periods after the adoption of the Regulation, were compared. Prescriptions in the primary health care setting were sorted by age group and drug and off-label status were determined. The number of off-label prescriptions issued by paediatricians was over two million per year. Prior to the adoption of the Paediatric Regulation, the off-label prescription rate was estimated at 7% of total prescriptions. Although the increase in the off-label rate over the study periods was mild, it was statistically significant (OR: 1.045; 95% CI: 1.043-1.046; p < 0.05). One of the most vulnerable population groups was neonates and infants up to 1 year, in which the off-label prescription rates showed the highest increase during the post follow-up period, which was statistically significant (OR: 4.270; 95% CI: 4.253-4.287; p < 0.05). The findings can help raise awareness and advocate for the development and authorization of medicines for children in the primary health care setting.

Prevention strategies to identify LASA errors: building and sustaining a culture of patient safety.

BACKGROUND: Potential look-alike, sound-alike (LASA) errors in outpatient and inpatient prescriptions have been widely described worldwide. However, most strategies of reducing drug name confusion have been only focused on the processes of prescribing and dispensing, often following local rules. MAIN TEXT: An illustrative recent example about this topic is given: the antidepressant Brintellix® (vortioxetine) (Takeda Pharmaceuticals USA, Inc.) and the antiplatelet medication Brilinta® (ticagrelor) (AstraZeneca LP). Revision of the initiatives that are currently applied to prevent potential LASA errors in different countries around the world and debate about the emerging strategies that could be implemented in short and mid-term. At present, a common policy worldwide on the authorization of unique names for innovative medicines does not exist. The implication of authorities in topdown strategies and the importance of developing an international health policy on the authorization of unique names for innovative medicines are highlighted in the following piece of opinion. CONCLUSIONS: Building and sustaining a culture of patient safety should be considered as a global top-down strategy which involved all the elements in the system (regulatory bodies, manufacturers and suppliers). The precedent established by the FDA in prevention strategies to identify and avoid LASA errors has been extremely important and should lead to international discussion. Coordinated international efforts are urgently needed in this area for the sake of patients' safety.

Adverse Drug Events in Patients with Dementia and Neuropsychiatric/Behavioral, and Psychological Symptoms, a One-Year Prospective Study.

Older people usually present with adverse drug events (ADEs) with nonspecific symptoms such as cognitive decline, recurrent falls, reduced mobility, and/or major deterioration. The aims of this study were to assess the ADEs of patients with dementia and presenting neuropsychiatric/behavioral, and psychological symptoms in dementia (BPSD) and to categorize and identify the principal factors that allow to prevent ADEs, and separately ADEs that result in falls. To that end, a one-year prospective study in a psychogeriatric ward (July 2015 to July 2016) was performed. All patients admitted to this ward were eligible for enrolment. Patients who met any of the following criteria were excluded from the study: Patients without cognitive impairment, a length of stay under 7 days, and palliative or previous psychiatric pathology. We included 65 patients (60% women, 84.9 years ± 6.7) with mild to moderate cognitive impairment, moderate to severe functional dependence, and a high prevalence of geriatric syndromes and comorbidity. A total of 87.7% were taking five or more drugs (mean 9.0 ± 3.1). ADEs were identified during the interdisciplinary meeting and the follow up by clinical record. Sixty-eight ADEs (81.5% patients) were identified, of which 73.5% were not related to falls. From these, 80% were related to drugs of the nervous system. The Naranjo algorithm determined that 90% of ADEs were probable. The severity of the ADEs was Category E in 34 patients (68%). The number of preventable ADE according to the Schumork⁻Thornton test was 58%. The main ADE was drowsiness/somnolence (27.7%). ADEs related to falls represented a 26.5%. The balance between effective treatment and safety is complex in these patients. A medication review in interdisciplinary teams is an essential component to optimize safety prevention.

Readability assessment of package leaflets of biosimilars.

OBJECTIVES: To assess the degree of readability and the length of the package leaflets of biosimilars. SETTING: The package leaflets analysed were downloaded from the European Medicines Agency (EMA) website. PARTICIPANTS: The study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35). DESIGN: This was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine. RESULTS: A considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects. CONCLUSIONS: Package leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.

Current evidence in the stability of medicines in dose administration aids: implications for patient safety.

INTRODUCTION: As the elderly population and polypharmacy are increasing, it is predicted that interventions to enhance medication adherence, as dose administration aids (DAA), will grow. One of the limitations of repackaging medicines into DAA is to assure the stability of medicines, and, therefore, their quality, efficacy and safety. AREAS COVERED: This article collects and summarises data of all the stability studies of repackaged medicines into DAAs. Computerized search in databases: PubMed, Google Scholar, SciELO, and reference texts related to the field (keywords: drug stability, DAAs, compliance aids, and repackaging), open access databases and guidelines. Also, it provides recommendations on the suitability of repackaging and compares them with those established. EXPERT OPINION: Since medicines are removed from primary package, their stability can be compromised due to psychochemical characteristics of the drug substance and product, the dosage form, the type of DAA selected, the co-storage and splitting, the repackaging conditions, and the conditions of storage. This review reflects the need of more standardized stability studies to guarantee the quality of repackaged medicines. In addition, the importance of them to support the pharmacist to make the best decisions in order to maximize outcomes and minimize risks related to patients' medication when repackaging it.

Assessing the stability of lamotrigine dispersible/chewable tablets when stored in blister punch cards.

OBJECTIVES: To determine the stability of lamotrigine dispersible/chewable tablets (DCTs) when stored in blister punch cards (BPCs). METHODS: Lamotrigine 100 mg DCTs were randomly repackaged into a US Pharmacopeia Class A 1 week cold-sealed BPC. Chemical and physical stability were evaluated over a 60 day period, in controlled conditions corresponding to Climatic Zones I/II (25 °C ± 2 °C; 60% ± 5% relative humidity). At scheduled times, various tests were performed on tablets in their primary packaging (reference samples) and on tablets repackaged (BPC samples). A validated high-performance liquid chromatography method adapted from the US Pharmacopeia was used to quantify lamotrigine. RESULTS: Lamotrigine content remained within the US Pharmacopeia acceptance range of 90%-110% during the 60 day study period and there were no significant changes compared with reference samples (p = .386). The increase of weight and the reduction of hardness of the repackaged tablets did not affect their dissolution profiles, and no change in appearance was observed. All tests complied with the compendial requirements of the pharmaceutical physical tests. CONCLUSIONS: Although changes in hardness after 14 days have not impacted on outcomes in terms of compliance with compendial requirements, a cautious recommendation would probably be a BPC storage of lamotrigine DCT of up to 14 days after repackaging.

Readability Analysis of the Package Leaflets for Biological Medicines Available on the Internet Between 2007 and 2013: An Analytical Longitudinal Study.

BACKGROUND: The package leaflet included in the packaging of all medicinal products plays an important role in the transmission of medicine-related information to patients. Therefore, in 2009, the European Commission published readability guidelines to try to ensure that the information contained in the package leaflet is understood by patients. OBJECTIVE: The main objective of this study was to calculate and compare the readability levels and length (number of words) of the package leaflets for biological medicines in 2007, 2010, and 2013. METHODS: The sample of this study included 36 biological medicine package leaflets that were downloaded from the European Medicines Agency website in three different years: 2007, 2010, and 2013. The readability of the selected package leaflets was obtained using the following readability formulas: SMOG grade, Flesch-Kincaid grade level, and Szigriszt's perspicuity index. The length (number of words) of the package leaflets was also measured. Afterwards, the relationship between these quantitative variables (three readability indexes and length) and categorical (or qualitative) variables were analyzed. The categorical variables were the year when the package leaflet was downloaded, the package leaflet section, type of medicine, year of authorization of biological medicine, and marketing authorization holder. RESULTS: The readability values of all the package leaflets exceeded the sixth-grade reading level, which is the recommended value for health-related written materials. No statistically significant differences were found between the three years of study in the readability indexes, although differences were observed in the case of the length (P=.002), which increased over the study period. When the relationship between readability indexes and length and the other variables was analyzed, statistically significant differences were found between package leaflet sections (P<.001) and between the groups of medicine only with regard to the length over the three studied years (P=.002 in 2007, P=.007 in 2010, P=.009 in 2013). Linear correlation was observed between the readability indexes (SMOG grade and Flesch-Kincaid grade level: r(2)=.92; SMOG grade and Szigriszt's perspicuity index: r(2)=.81; Flesch-Kincaid grade level and Szigriszt's perspicuity index: r(2)=.95), but not between the readability indexes and the length (length and SMOG grade: r(2)=.05; length and Flesch-Kincaid grade level: r(2)=.03; length and Szigriszt's perspicuity index: r(2)=.02). CONCLUSIONS: There was no improvement in the readability of the package leaflets studied between 2007 and 2013 despite the European Commission's 2009 guideline on the readability of package leaflets. The results obtained from the different readability formulas coincided from a qualitative point of view. Efforts to improve the readability of package leaflets for biological medicines are required to promote the understandability and accessibility of this online health information by patients and thereby contribute to the appropriate use of medicines and medicine safety.

Stability of enalapril repackaged into monitored dosage system.

A monitored dosage system (MDS) is a professionally prepared blister-type repackaging system used to improve medication adherence. The objective of this study was to determine the stability of enalapril tablets, a widely prescribed drug, commonly used by the elderly but potentially unstable in MDSs. No degradation of enalapril tablets repackaged into MDSs was observed during the 60 day study period.

Is the pharmacokinetics of bupivacaine equivalent after lumbar epidural administration through a needle or a catheter in male and female adults?

We assessed possible pharmacokinetic modifications due to different epidural injection techniques using either a needle or a catheter. Adult patients (n=23) undergoing lower abdominal or lower extremity surgery were randomly assigned a single bupivacaine epidural injection anesthesia (0.5%, 15 mL, 0.3 mL/s) through needle or catheter device. Plasma bupivacaine concentration was quantified using a validated HPLC method and non-compartmental pharmacokinetic parameters estimated. CMAX and TMAX were similar in both groups: 952 ± 346 ng/mL, 0.65 ± 0.5 1h in the needle group; 810 ± 307 ng/mL, 0.43 ± 0.29 h in the catheter group respectively. Plasma AUC0→∞ was also similar in both groups: 3868 ± 1687 ngh/mL for needle versus 4096 ± 1748 ngh/mL using catheter. The catheter group showed slower disposition than the needle group: t1/2=3.9 ± 2.3 h, MRT=6.0 ± 3.1 h versus 2.7 ± 1.03 h and 4.5 ± 1.2 h with needle administration respectively though it did not reach statistical significance, Cl/F and V/F were also similar. Lastly, female patients showed significant longer t1/2 after administration through catheter (5.7 ± 2.0 h) than needle (2.7 ± 0.6 h) group (P=0.0279). The device type does not affect the pharmacokinetics which is similar in both groups although sex-based differences might exist.

Evaluation of electronic prescription implementation in polymedicated users of Catalonia, Spain: a population-based longitudinal study.

OBJECTIVES: To assess whether electronic prescribing is a comprehensive health management tool that may contribute to rational drug use, particularly in polymedicated patients receiving 16 or more medications in the public healthcare system in the Barcelona Health Region (BHR). DESIGN: 16 months of retrospective study followed by 12 months of prospective monitoring. SETTING: Primary healthcare in BHR, Catalonia, Spain. PARTICIPANTS: All insured patients, especially those who are polymedicated in six basic health areas (BHA). Polymedicated patients were those with a consumption of ≥16 drugs/month. INTERVENTIONS: Monitoring demographic and consumption variables obtained from the records of prescriptions dispensed in pharmacies and charged to the public health system, as well as the resulting drug use indicators. Territorial variables related to implementation of electronic prescribing were also described and were obtained from the institutional data related to the deployment of the project. MAIN OUTCOME MEASURES: Trend in drug use indicators (number of prescriptions per polymedicated user, total cost per polymedicated user and total cost per prescription) according to e-prescription implementation. RESULTS: There was a significant upward trend in the number of polymedicated users, number of prescriptions and total cost (p<0.05), which seemed independent from the implementation of electronic prescribing when comparing the preimplementation and postimplementation period. Prescriptions per user and cost per user showed a decrease between the preimplementation and postimplementation period, being significant in two BHAs (p<0.05). CONCLUSIONS: Results suggest that after the implementation of electronic prescribing, the rationality of prescribing in polymedicated patients improved. In addition, this study provides a very valuable approach for future impact assessment.

Readability assessment of package inserts of biological medicinal products from the European medicines agency website.

BACKGROUND: Package inserts that accompany medicines are a common source of information aimed at patients and should match patient abilities in terms of readability. OBJECTIVE: Our objective was to determine the degree of readability of the package inserts for biological medicinal products commercially available in 2007 and compare them with the readability of the same package inserts in 2010. METHODS: A total of 33 package inserts were selected and classified into five groups according to the type of medicine: monoclonal antibody-based products, cytokines, therapeutic enzymes, recombinant blood factors and other blood-related products, and recombinant hormones. The package inserts were downloaded from the European Medicines Agency website in 2007 and 2010. Readability was evaluated for the entire text of five of the six sections of the package inserts and for the 'Annex' when there was one. Three readability formulas were used: SMOG (Simple Measure of Gobbledygook) grade, Flesh-Kincaid grade level, and Szigriszt's perspicuity index. RESULTS: No significant differences were found between the readability results for the 2007 package inserts and those from 2010 according to any of the three readability indices studied (p>0.05). However, there were significant differences (p<0.05) between the readability scores of the sections of the package inserts in both 2007 and 2010. The readability of the package inserts was above the recommended sixth grade reading level (ages 11-12) and may lead to difficulties of understanding for people with limited literacy. CONCLUSIONS: All the sections should be easy to read and, therefore, the readability of the medicine package inserts studied should be improved.

Profile, cost and pattern of prescriptions for polymedicated patients in Catalonia, Spain.

OBJECTIVES: Polypharmacy is one of the main management issues in public health policies because of its financial impact and the increasing number of people involved. The polymedicated population according to their demographic and therapeutic profile and the cost for the public healthcare system were characterised. DESIGN: Cross-sectional study. SETTING: Primary healthcare in Barcelona Health Region, Catalonia, Spain (5 105 551 inhabitants registered). PARTICIPANTS: All insured polymedicated patients. Polymedicated patients were those with a consumption of ≥16 drugs/month. MAIN OUTCOMES MEASURES: The study variables were related to age, gender and medication intake obtained from the 2008 census and records of prescriptions dispensed in pharmacies and charged to the public health system. RESULTS: There were 36 880 polymedicated patients (women: 64.2%; average age: 74.5±10.9 years). The total number of prescriptions billed in 2008 was 2 266 830 (2 272 920 total package units). The most polymedicated group (up to 40% of the total prescriptions) was patients between 75 and 84 years old. The average number of prescriptions billed monthly per patient was 32±2, with an average cost of €452.7±27.5. The total cost of those prescriptions corresponded to 2% of the drug expenditure in Catalonia. The groups N, C, A, R and M represented 71.4% of the total number of drug package units dispensed to polymedicated patients. Great variability was found between the medication profiles of men and women, and between age groups; greater discrepancies were found in paediatric patients (5-14 years) and the elderly (≥65 years). CONCLUSIONS: This study provides essential information to take steps towards rational drug use and a structured approach in the polymedicated population in primary healthcare.

Los sistemas personalizados de dosificación en vídeo como herramienta docente en la farmacia clínica y la atención farmacéutica / A video on monitored dosage systems as a teaching tool in clinical pharmacy and pharmaceutical care

Objetivo. Difundir un vídeo como herramienta docente que pretende potenciar los objetivos de aprendizaje previamente definidos en un modelo conceptual que integra el sistema de salud y el proceso de formación del futuro profesional farmacéutico. Material y métodos. En el diseño se decidió el tipo de vídeo (alta potencialidad expresiva), finalidad (complemento de la formación) y temática (los sistemas personalizados de dosificación o SPD). Posteriormente, se llevaron a cabo las fases de elaboración: documentación, guionización, grabación y edición. El equipo estuvo formado por docentes, becarios, colaboradores y expertos en comunicación audiovisual. La grabación requirió, entre otros, material para el servicio SPD según procedimiento, el aula de simulación asistencial, un laboratorio y una farmacia comunitaria. Resultados. Se obtiene un vídeo titulado Los sistemas personalizados de dosificación como herramienta en la atención farmacéutica para la mejora de la adherencia al tratamiento y el éxito terapéutico, que complementará la sesión práctica realizada por los alumnos sobre Farmacoterapia individualizada: SPD, de la asignatura obligatoria Farmacia Clínica y Atención Farmacéutica del Grado de Farmacia de la Universidad de Barcelona. La estructura narrativa incluye los apartados: introducción, descripción del SPD, seguimiento farmacoterapéutico con SPD, equipamiento y material, procedimiento, visitas de seguimiento y conclusiones. Conclusiones. El vídeo sobre los SPD se constituye en una herramienta docente a disposición de los alumnos y el público en general, que favorecerá los objetivos de aprendizaje de competencias específicas del futuro graduado en farmacia, y fuente de información especialmente para los propios farmacéuticos con ejercicio profesional asistencial (AU)

Aim. To divulge a video as a teaching tool in order to enhance the learning objectives previously defined in a conceptual model which integrates both the health system and the training process of future professional pharmacists. Material and methods. The design included the type of video (high expressive potential), purpose (educational complement) and topic (Monitored Dosage Systems or MDS). Subsequently, the video development was conducted through a series of phases involving documentation gathering, script making, video shooting and final editing. The team consisted of teachers, scholarship students, contributors and experts in audiovisual communication. The video recording required material for the MDS service according to a protocol, a healthcare simulation classroom, a laboratory and a community pharmacy, among others. Results. The result is a video entitled The Monitored Dosage Systems as a tool in pharmaceutical care to improve treatment adherence and therapeutic success, which will complement the students’ practical session on Individualized pharmacotherapy: MDS, of the compulsory subject Clinical Pharmacy and Pharmaceutical Care of pharmacy degree from the University of Barcelona. The narrative structure of the video includes the following sections: Introduction, Description of MDS, Pharmacotherapy follow-up by MDS, Material and equipment, Procedure, Monitoring visits and Conclusions. Conclusions. The video on the MDS constitutes a teaching tool available to students and general audience, which will improve the learning objectives of specific competencies of the future pharmacy graduate, and serve as a source of information especially for pharmacists as healthcare professionals (AU)

Farmacia galénica y medicamentos huérfanos / No disponible

No disponible