ATC Level Research Articles

The prevalence of polypharmacy in older Europeans: A multi-national database study of general practitioner prescribing.

The aims of this study were to measure the prevalence of polypharmacy and describe the prescribing of selected medications known for overuse in older people with polypharmacy in primary care. This was a multinational retrospective cohort study across six countries: Belgium, France, Germany, Italy, Spain and the UK. We used anonymized longitudinal patient-level information from general practice databases hosted by IQVIA. Patients ≥65 years were included. Polypharmacy was defined as having 5-9 and ≥10 distinct drug classes (ATC Level 3) prescribed during a 6-month period. Selected medications were: opioids, antipsychotics, proton pump inhibitors (PPI), benzodiazepines (ATC Level 5). We included country experts on the healthcare context to interpret findings. Age and gender distribution was similar across the six countries (mean age 75-76 years; 54-56% female). The prevalence of polypharmacy of 5-9 drugs was 22.8% (UK) to 58.3% (Germany); ≥10 drugs from 11.3% (UK) to 28.5% (Germany). In the polypharmacy population prescribed ≥5 drugs, opioid prescribing ranged from 11.5% (France) to 27.5% (Spain). Prescribing of PPI was highest with almost half of patients receiving a PPI, 42.3% (Germany) to 65.5% (Spain). Benzodiazepine prescribing showed a marked variation between countries, 2.7% (UK) to 34.9% (Spain). The healthcare context information explained possible underreporting for selected medications. We have found a high prevalence of polypharmacy with more than half of the older population being prescribed ≥5 drugs in four of the six countries. Whilst polypharmacy may be appropriate in many patients, worryingly high usage of PPIs and benzodiazepines supports current efforts to improve polypharmacy management across Europe.

Polypharmacy Independently Predicts Overall Survival in Patients with Lymphoid Cancer

Introduction Comorbidity is common among patients with lymphoid cancer (LC) and may limit treatment options. Often, comorbidity is accompanied by medication leading to polypharmacy in multimorbid patients. Whereas comorbidity is difficult to eliminate, discontinuing inappropriate medication may offer an attractive modifiable risk. Aim To investigate the effect of polypharmacy and comorbidity on overall survival (OS) in patients with LC. Methods We retrieved data on all Danish patients registered with chronic lymphocytic leukemia (CLL) from the Danish CLL Register since 2008 and with mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma (FL) from the Danish Lymphoma Register since 2005. All patients were diagnosed before June 2019; those with more than one LC diagnosis were excluded. Baseline data were used to calculate international prognostic indices (IPI). International Classification of Diseases (ICD10) diagnosis codes were retrieved from the Danish Patient Register, and Charlson comorbidity index (CCI) scores were calculated (Quan et al., Am J Epidemiol, 2011) at time of LC diagnosis. All patients were given a hematological CCI score of 2. Information on medication prescribed within the year up until LC diagnosis was retrieved from the Danish Prescription Register, and the number of drug classes (using the third ATC level, e.g. C03) was used to define polypharmacy as at least 5 drug classes. OS was calculated from time of diagnosis until death or end of follow-up. Multivariable analyses were equally adjusted for CCI, polypharmacy, and appropriate IPI. Results We identified 15,314 patients with LC including 5155 with CLL, 953 with MCL, 6182 with DLBCL, and 3024 with FL. The median age was 69 years (IQR 60;76). CLL-IPI and R-IPI are provided in the Figure. MIPI was low, intermediate, and high in 137 (15%), 297 (32%), and 493 (53%) patients, respectively, and FLIPI2 was low, intermediate, and high in 391 (16%), 1469 (62%), and 518 (22%), respectively. The median CCI score was 2 (including the hematological CCI score of 2, IQR 2;2). Most common comorbidities included chronic pulmonary disease (5%), congestive heart failure (CHF; 3%), rheumatic disease (RD; 3%), and metastatic cancer (MC; 2%). MC (3% vs 1-2%), RD (4% vs 2%), and AIDS (0.3% vs 0.0%) were significantly more prevalent in DLBCL as compared with other LCs ( P≤0.00054). Patients had most frequently been prescribed antibacterial (J01; 50%), analgesic (N02; 40%), renin-angiotensin system (C09; 33%), antithrombotic (B01; 32%), lipid modifying (C10; 30%), anti-inflammatory/rheumatic (M01; 29%), dyspepsia related (A02; 27%), and diuretic (C03; 27%) drugs. Antibacterials (54% vs 46-51%), analgesics (46% vs 33-36%), dyspepsia related (32% vs 22-28%), anti-inflammatory/antirheumatic (33% vs 24-28%), and systemic corticosteroid (H02; 13% vs 6-8%) drugs were being prescribed significantly more often in patients with DLBCL as compared with those with other LCs ( P<0.0001). In multivariable analyses adjusted for disease specific IPIs and CCI (2 vs >2), polypharmacy (<5 vs ≥5) was an independent prognostic marker of OS in CLL (hazard ratio [HR] 1.7, 95% confidence interval [CI]; 1.5;2.0), MCL (HR 1.4, 95% CI 1.2;1.7), DLBCL (HR 1.6, 95% CI 1.5;1.8), and FL (HR 1.8, 95% CI 1.6;2.1; P<0.0001). Using polypharmacy as a continuous variable (0-2 vs 3-4 vs 5-6 vs 7-8 vs 9-10 vs >10), we further demonstrated a dose-response effect on OS in CLL, DLBCL (Figure), MCL, and FL (data not shown). Similar to CLL and DLBCL, FL with >2 drug classes were significantly associated with shorter OS, whereas in MCL, polypharmacy groups were small ( n≤262) and only significantly associated with shorter OS for groups with ≥5 drug classes. Conclusion Polypharmacy is an important prognostic marker of OS independent of the CCI and IPIs in CLL, MCL, DLBCL, and FL. Polypharmacy is most likely a result of an underlying comorbidity, still informing the prognosis further than register based CCI scores. Further studies will seek to clarify the extent of medication that may be considered for discontinuation in newly diagnosed patients. Moreover, these results indicate that consistent collection of data on both comorbidity and polypharmacy at baseline in clinical trials may improve subgroup analyses and clinical translation of results. This is particularly important when extrapolating clinical trial results to ineligible populations.

Trends in National Pharmaceutical Expenditure in Korea during 2011 - 2020.

This study aimed to identify the trends in pharmaceutical expenditure (PE), share of PE in health expenditure (HE), and trends in expenditure by pharmacological groups (ATC level 1 classification) in Korea for a 10-year period (2011 - 2020) and compare the data with those of other Organisation for Economic Co-operation and Development (OECD) countries. Using the findings, we determined the current status of pharmaceutical expenditure (PE) management in Korea and derived the implications for establishing future macroscopic policies on PE. We analyzed the OECD Health Statistics and the Korean national health insurance claims database from January 2011 through December 2020. The outcome measures were HE, PE, and pharmaceutical sales data for ATC level 1 medicines from OECD Health Statistics data during 2011 - 2020. As OECD collects limited ATC level 1 data, we used the HIRA health insurance claims data for PEs of ATC level-1 classification, including D, L, P, and S. PE in Korea increased by 38.5% from 19.9 billion USD in 2011 to 27.6 billion USD in 2020, whereas the share of PE in HE decreased by 6.3%p from 26.4% in 2011 to 20.1% in 2020. In 2020, Korea ranked third in PE per capita (760.9 USD PPP) and had the highest share of PE (20.1%) among the 19 OECD countries studied. By ATC level 1 class, the highest PE was A (alimentary tract and metabolism) at 4.3 billion USD, and L (antineoplastic and immunomodulating agents) had the highest increase at 13.4%; in contrast, J (anti-infectives for systemic use) had the lowest increase in annual average PE at -0.2% in 2020 relative to 2011. Among the 17 OECD countries, Korea had the highest and the third-highest expenditures for ATC codes A and J, respectively. PE in Korea has continued to increase between 2011 and 2020, indicating the need for macroscopic management of PE. Our results on PE by ATC code may help health authorities in establishing future policies on PE.

Massive presence of off-label medicines in Danish neonatal departments: A nationwide survey using national hospital purchase data.

There is currently insufficient knowledge of gestational age dependent medicine disposition in neonates. Accordingly, the use of off-label medication, i.e., use of medicines outside its approved marketing authorization, is high in the neonatal departments. By using data from the Danish National Pharmaceutical Hospital Purchase Database, we identified the most commonly occurring medications and calculated the on/off-label ratios for premature and term neonates. Data was extracted on ATC level 5 and based on defined daily doses as per WHO. Data covered the 4 high-level NICUs and 10 of 13 of the intermediate/standard level Danish neonatal departments. Of the identified medication, 87% and 70% did not have approved marketing authorization for use in premature and full-term neonates, respectively. Furthermore, one-fifth of the top 100 medicines did not have a (Danish) marketing license. Overall, off-label medication was widespread covering virtually all ATC groups and no ATC group had an off-label level lower than 50% (range 50%-100%). Finally, in 21% of medications, additives from 8 different chemical groups with potential deleterious effects for neonates were identified. In conclusion, off-label medication in the Danish neonatal departments is widespread. The pharmaceutical industry is unlikely to solve this problem, and we may for a very long time be occasionally forced to use off-label medication. Practical solution must therefore come from multidisciplinary clinical and academic collaboration. Use of formulation list as guidance for prescriptions and NICU-friendly galenic formulations may mitigate the problem temporarily while waiting for definitive studies.

Consumption of oral anticancer drugs in Norway compared by different units of measurements – introduction of new DDDs

Background: Antineoplastic agents (ATC group L01) have not been assigned DDDs due to highly interindividualvariation in dosages. Consumption data has therefore been presented in other measurement units such as grams of active ingredient. However, the protein kinase inhibitors (PKIs) are a rapidly growing drug group that was introduced to the market recently and are administered orally in a fixed dose. DDDs were therefore established for the PKIs in 2020. In this study we aim to assess whether the newly assigned DDDs would better express drug utilisation patterns in Norway than the current units of measurement.Methods: Sales data for PKIs (ATC level L01E) by grams, cost, units and packages for 2019 were collectedfrom the Norwegian Drug Wholesales Statistics and data on number of prescriptions and prevalence for 2019were collected from the Norwegian Prescription Database (NorPD). DDDs were calculated by applying thevalues of the new DDDs.Results: The proportions of the different substances varied according to the unit of measurement. DDDs andpackages had the highest similarity and correlated better than grams with the prevalence of use in theNorwegian population. BCR-ABL tyrosine kinase inhibitors was the largest group accounting for 31% ofthe total consumption (DDD/1000 inhabitants/day) and imatinib was the most sold PKI in all units of measurement except cost.Conclusions: Using an international agreed unit of measurement gives reliability to the study result. Assignment of DDDs to PKIs will improve the quality of drug utilisation studies in this area.

Trends and patterns in EU(7)-PIM prescribing to elderly patients in Germany.

The aim of this study was to explore patterns and long-term development in prescribing potentially inappropriate medication (PIM) according to the EU(7)-PIM list to elderly patients in Germany. We analysed anonymized German claims data. The study population comprised 6.0 million insured individuals at least 65years old, including all their prescriptions reimbursed in 2019. For the analysis of long-term development, we used data for the years 2009-2019. Factors associated with PIM prescribing were considered from two perspectives: patient-oriented analysis was performed with logistic regression and prescriber-oriented analysis was performed with multiple linear regression. EU(7)-PIM prevalence was reduced from 56.9% in 2009 to 45.1% in 2019. Average annual volume (DDDs/insured) decreased from 145 in 2009 to 121 in 2019. These figures are substantially greater than those for the older PRISCUS list. The majority of investigated ATC level 2 groups with the highest EU(7)-PIM DDD volume exhibited substantial decreases; moderate increases were found for antihypertensive and urological drugs. Antithrombotics increased strongly with the introduction of direct oral anticoagulants. The most prevalent EU(7)-PIM medication was diclofenac; however, in the age group 85+ years, apixaban was twice as prevalent as diclofenac. Polypharmacy, female sex, age < 90years, need for nursing care and living in Eastern regions were identified as risk factors. Prescriber specialty was the most marked factor in the prescriber-oriented analysis. Although the use of EU(7)-PIMs has been declining, regional differences indicate considerable room for improvement. The comparison with PRISCUS highlights the necessity of regular updates of PIM lists.

Unexpected beneficial effects of drugs: an analysis of cases in the Dutch spontaneous reporting system.

Drug use is inherently related to both beneficial effects on health as well as the occurrence of risks. The beneficial effects may be related to efficacy, the treatment range of a product, or even to user-friendliness of a product. However, in addition to the occurrence of adverse drug reactions, a drug can also have an unexpected beneficial effect on a patient's health, not related to the indication for which the drug was used. The aim of this article is to characterize the reports of unexpected beneficial effects of drugs in the Dutch spontaneous reporting system. A descriptive analysis was used to gain insight in number of reports and drug classes responsible for unexpected beneficial effects of drugs. Grouping of positive side effects into classes was done by a conventional qualitative content analysis of the cases. Four hundred nine reports which described unexpected beneficial effects of drugs were included, which mentioned 451 associations between suspected drugs and unexpected beneficial effects. There were 147 drug classes on the 4th ATC level involved. Content analysis of the reports gave rise to 22 categories of unexpected beneficial effects of drugs, including one "other category". DISCUSSIONAND CONCLUSION: The analysis showed a diverse spectrum of reported reactions and drugs with some categories of unexpected beneficial effects of drugs mentioned multiple times for certain drug classes on the 4th ATC level. Most of these findings are consistent with the existing literature and knowledge on the pharmacological mechanism of the drugs in question. Coding harmonization would make it possible to study these effects in international databases.

Medication use among older people in Europe: Implications for regulatory assessment and co-prescription of new medicines.

AimsThe aim of this study was to elucidate drug prescription patterns in older European people with the objective to support regulatory contextualisation of (1) the suitability of enrolment criteria for new clinical trials; and (2) the understanding of the potential interactions/incompatibilities of newly authorised medicines with those most frequently used by older people.MethodsMedicines agencies in Portugal, Poland, Slovakia and England were approached to provide a list of the 10 most frequent prescriptions in 2016 for systemically used medicines per active substances (i.e. ATC level 5), in older people. For each active substance and for the most common therapeutic subgroups (i.e. ATC level 2), the percentages of older patients receiving at least one prescription were calculated per older age categories (65–74; 75–84; 85+) and gender.ResultsThere was considerable alignment in the most commonly prescribed active substances and therapeutic subgroups represented; these were gastroprotectants (A02), lipid‐modifying agents (C10) and analgesics (N02). Some gender differences were observed (A02 and N02 were prescribed more frequently to women), but trends on age categories were consistent; A02 and N02 prescriptions continued to rise with age, while C10 slightly decreased in the 85+ age group in all countries.ConclusionsThe findings of this study are consistent with the major chronic diseases reported in the older European population. Evidence on co‐medication of newly applied medicines with the currently identified most commonly used medicines in older people should be generated during the (non)clinical development of new medicines to support regulatory assessment and adequate user information.

Drug-induced vitiligo: a case/non-case study in Vigibase® , the WHO pharmacovigilance database.

Vitiligo is a common depigmenting disorder ensuing the loss of epidermal melanocytes. It is a multifactorial disease with immunological, genetic and environmental factors including drug exposure. The purpose of the study was to investigate the drugs and therapeutic subclasses associated with vitiligo occurrence reported in VigiBase® , the WHO pharmacovigilance database. A case/non-case study was carried out by defining cases as vitiligo reports and non-cases as all other reports. The reporting odds ratio (ROR) was calculated for the 'suspected' drugs and drug classes according to ATC level 4. During the study period, 741 cases of vitiligo were registered. Mean age was 49±20years. The disproportionality analysis showed an association between vitiligo and pembrolizumab (ROR 116.9, 95% Confidence Interval (CI) 94.8, 144.3), nivolumab (ROR 22.6, 95% CI 15.8, 32.4), ipilimumab (ROR 41.7, 95% CI 25.0, 69.7), imiquimod (ROR 152.8, 95% CI 103.0, 226.7), adalimumab (ROR 3.8, 95% CI 2.5,5.8), infliximab (ROR 2.6, 95% CI 1.65, 4.01), alemtuzumab (ROR 27.8, 95% CI 17.6, 43.9), and ustekinumab (ROR 9.3, 95% CI 5.6, 15.6). Concerning the pharmacological classes ATC level 4, a significant association was found with monoclonal antibodies, interferons, selective immunosuppressants, TNF-alpha inhibitors, interleukin inhibitors, and topical antivirals. This study confirmed the expected associations between vitiligo and immune checkpoint inhibitors and strengthened the emerging signal about the association between vitiligo and imiquimod, TNF-alpha inhibitors and interferons. New signals were shown with selective immunosuppressants including alemtuzumab and interleukin inhibitors.

PDG48 AN ANALYSIS OF THE DANISH MODEL FOR ANALOGUE COMPETITION OF HOSPITAL MEDICINE BASED ON THE THERAPEUTIC AREA, HEPATITIS C

The expenses for hospital pharmaceuticals in Denmark has increased more than 80% the last decade. The increased expenditure is particularity caused by new and expensive patent-protected medicine. Amgros carries out EU-tender calls for 98% of hospital medicine used at public hospitals in Denmark. The opportunity to achieve price discounts on patent-protected pharmaceuticals through tender calls are minimal due to the limited competition. In order to accommodate this, a unique analogue competition model was developed by Amgros and the Danish Regions. The purpose of this study was to explore the effects of the analogue competition model on pharmaceutical prices in the therapeutic area hepatitis C in the period from 2014-2018. The study was designed as a case study including semi-structured interviews with relevant stakeholders in the industry, Danish Regions, and Amgros. Quantitative data including both list prices and actual purchase prices were withdrawn with special permission from Amgros´ database. The qualitative and quantitative analysis showed that the price for one hepatitis C treatment decreased 77% (from 531.406 DKK to 121.798 DKK per patient) for genotype 1 and 32% (from 531.406 DKK to 363.780 DKK per patient) for genotype 3 within the period 2014-2018. Important factors leading to the price decreases were the following: the therapeutic treatment guidelines produced by the Danish Medicines Council equalling the medicine at ATC level 5, the number of pharmaceuticals for each disease genotype on the market at each tender, the incentive structure created by the Amgros tender system with possibilities of being ranked as first choice with an 75% market share, and the size of the patient population. The analysis showed that the analogue model was effective in creating an oligopoly competition market situation within the therapeutic area hepatitis C.

Analysis of the fall-related risk of pharmacotherapy in Czech hospitals: A case control study.

Falls are among the major problems occurring in hospital setting, when drugs are viewed as important modifiable risk factor of falling. The aim was to analyse the effect of pharmacotherapy on the risk of falls in hospitalized patients. A multicentre prospective case-control study was conducted in 2017 retrieving data from four hospitals in South Bohemia, Czech Republic. An online database was constructed to collect patient and fall-related data. Each fall that occurred during hospitalization was assigned to appropriate controls (no fall during hospitalization) based on gender, age, length of hospitalization, and the number of drugs. Univariate and multivariate correlations were performed with a significance level of P < .05. A total of 222 fall cases (107 males; median age, 81 y) and 1076 controls (516 males; median age, 80 y) were included. According to the first ATC level classification, drugs from groups S, N, and P were significantly associated with fall-related risk compared with controls (P < .05); further analysis of ATC levels showed that only psycholeptics (N05), antipsychotics (N05A), and tiapride were significantly associated with falls. Regression analysis revealed use of psycholeptics N05 (OR = 2.06; 95% CI, 1.56-2.76), or ophthalmologicals S01 (OR = 2.72; 95% CI, 1.37-5.41), as factors with the highest fall-related risk. Apart from the commonly considered fall-risk increasing drugs, other groups, such as ophthalmologicals, should also be considered; however, regarding clinical practice, it is difficult to evaluate the effects of individual drugs in the context of other risk factors of falls, due to the multifactorial nature of falls.

Changes in prescription patterns in older hospitalized patients: the impact of FORTA on disease-related over- and under-treatments.

Physicians often face difficulties in choosing appropriate medications for multimorbid older people. The FORTA (Fit for the Aged) classification (A: absolutely, B: beneficial, C: careful, D: don't) was proposed as a clinical tool for improving the quality of drug treatment in the aged. As an implicit tool, FORTA has been shown to aid medication optimization and improve clinical end points in the VALFORTA trial. In this prospective randomized controlled study, 207 older hospitalized patients received standard geriatric treatment and 202 patients received FORTA-guided treatment. Here, changes of drug prescriptions at the anatomical-therapeutic-chemical system (ATC) level were evaluated separately for important diagnoses in descriptive analyses; over- and under-treatment rates were compared between groups. At the individual drug/drug class level related to all important diagnoses, the application of FORTA significantly improved under-treatments for 12 drugs/drug classes (e.g., ACE inhibitors to treat arterial hypertension) and over-treatments for 7 drugs/drug classes (e.g., proton pump inhibitors to treat gastroesophageal reflux disease). FORTA representing the first combined positive/negative labeling approach at the individual drug level aids the optimization of drug treatment in older people as detected for drugs/drug classes at the ATC level in important indications. FORTA is effective in addressing over- and under-treatments even if analyzed for smaller subgroups of VALFORTA.

Development of one paediatric and one neonatal formulary list in hospital settings.

The aim of this study is to describe the stepwise process towards creating two formulary lists: one for paediatric and one for neonatal patients covering common diseases in hospital settings. This study presents the concept for developing a formulary list, namely how to: (1) organize the editorial board, (2) procure drug consumption data and database management, including information on labelling status, dosing options, excipients and problematic adverse events, current guidelines, evidence and price, (3) develop the first edition for the formulary list and formulary manual, and (4) to establish a paediatric sub-committee within the Regional Drug and Therapeutic Committee to maintain and continually develop the two formularies. The total number of drugs was 411 ATC level 5, which covers 1097 unique item numbers prior to the paediatric formulary list, of which 263 item numbers were included in the final list. In neonates, 201 drugs ATC level 5 were evaluated, covering 348 unique item numbers, of which 104 item numbers were included in the final neonatal formulary list. Eighty-eight percent of the included drugs in the paediatric formulary were licensed to children (not specified by age group), 2% were unlicensed in Denmark, and 7% were extemporaneous preparations. For neonates, the percentage was 48%, 4% and 16%, correspondingly. The process is time-consuming as studies are lacking and age-appropriate dosage forms and concentrations differ amongst countries. Nevertheless, the process should be somewhat similar between countries, albeit different drugs may be selected for the final formulary lists.

Antibiotic utilisation in adult and children patients in Kosovo hospitals

ObjectivesThere are no reliable data on antibiotic use in Kosovo hospitals. The aim of this survey was to monitor volumes and patterns of antibiotic use in hospitalised patients in order...

Use of medicines by patients of the primary health care of the Brazilian Unified Health System.

ABSTRACTOBJECTIVE To characterize the use of medicines by patients of the primary health care of the Brazilian Unified Health System (SUS).METHODS This is a cross-sectional, exploratory, and descriptive study, part of the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos – Serviços, 2015 (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines – Services, 2015). Interviews were carried out with patients present in the services by semi-structured questionnaires. Sociodemographic, clinical, and use of medicines variables were assessed and the use of medicines in the 30 days prior to the interview was also verified. The population was stratified into three age groups: 18 to 44, 45 to 64, and 65 years or more. The differences between the age groups were verified using the Student’s t-test for continuous variables and chi-square test for the categorical ones. The complex samples analysis plan was employed. The medicines were classified according to the Anatomical Therapeutic Chemical Classification System.RESULTS Of the 8,803 patients interviewed, 6,511 (76.2%) reported to have used medicines in the 30 days prior to the interview. On average, each patient used 2.32 medicines, without difference between the sexes. Among medicine users, 18.2% were aged 65 years or more. Compared to the other age groups, older adults presented more comorbidities, used more medicines, and self-reported worse health conditions. They were also less educated, reported worse economic situation, and lived alone. The medicines that were mostly used were “other analgesics and antipyretics” (3rd ATC level) and Losartan (5th ATC level).CONCLUSIONS Most medicine users had lower education level and presented comorbidities. The most used medicines were the antihypertensive ones. Self-medication was higher among young people. Most patients reported to use generic medicines. The average number of medicines and the prevalence of use increased with age. Due to the characteristics observed and the difficulties in the use of medicines, older adults are in a situation of greater vulnerability.

Analysis of drug use in institutionalized individuals with intellectual disability and tube feeding

Objectives: Little is known about the medication used by people with intellectual disabilities (ID) and enteral feeding tube (EFT). However, in light of the complexity associated with drug administration through EFT, data on medication use in this population may be helpful in the development of practical guidelines and staff training initiatives.Methods: A cross-sectional, observational study was conducted in six Belgian residential care facilities (RCFs) for individuals with ID. Anonymized medication records of all residents receiving chronic medication through EFT were collected (n = 156). All chronic drugs were categorized according to the ATC classification, and medication records were checked for potential major drug–drug interactions (DDI).Results: The 156 residents used a total of 1029 chronic drugs via EFT, with a median of six drugs per resident (range 1–14). A total of 148 different drug molecules were identified, belonging to 38 main ATC therapeutic groups (ATC level 2). Antiepileptics, drugs for constipation and drugs for acid-related disorders were the most frequently used groups. Seventy-four of the 156 screened medication records (47%) contained at least one potential DDI; in total, 116 potential interactions were identified, which represent 38 different interacting drug pairs.Conclusion: This study describes medication use through EFT among people with ID in Belgian RCFs, with antiepileptics being the most frequently used group. Our study also demonstrated that a high number of drugs is administered through EFT, and that the number of potential DDIs is high. These observations warrant an increased attention for drug administration through the EFT in individuals with ID.

Patterns of psychotropic medicine use in pregnancy in the United States from 2006 to 2011 among women with private insurance.

BackgroundPsychiatric disorders are equally common during pregnancy as among non-pregnant women, and many of these conditions are treated with psychotropic medicines. Relatively little is known about patterns of use of many these agents during pregnancy, and specifically of how rates may have shifted during the last decade. We aimed to quantify the rate of pregnancy related exposures to categories of psychotropic medicines stratified according to the primary indication for use (antidepressants, antipsychotics, anxiolytics, and psychostimulants), trimester of pregnancy, trends over time and region, and indication for use.MethodsWe conducted a retrospective cohort study of pregnancies among women in the Truven Health MarketScan database (source population 70 million Americans), which captures person-specific clinical use and includes detailed information on filled prescriptions, hospitalizations and outpatient visits for all privately insured employees and their dependents. We classified psychotropic medicines of interest using ATC level 3 accordingly: antipsychotics (N05A); anxiolytics (N05B); antidepressants (N06A); psychostimulants, agents used for ADHD and cognitive enhancement (N06B). We also examined temporal and regional trends in use.ResultsWe included 343,299 women who had a live birth between Jan 1, 2006 and Dec 31, 2011, of whom 10.3% were dispensed one or more psychotropic medicines during pregnancy. This rate varied from 6% to 15% between states. The rate of use of psychotropic medicines was relatively stable between 2006 and 2011. The most commonly used psychotropic medicines were selective serotonin reuptake inhibitors (5.1%) and benzodiazepine or benzodiazepine-like medicines (3.9%). Among psychotropic users, the most commonly associated psychiatric diagnosis was depression (25.0%), followed by anxiety disorders (24.4%). Approximately 1.6% of women used more than one category of psychotropic medicine in pregnancy, most commonly an antidepressant and an anxiolytic medicine (1.2%).ConclusionsGiven this relatively high rate of use, the lack of evidence that the most frequently used medications improve birth outcomes and the safety concerns associated with both early and late pregnancy use for many frequently-used medications, there is a need for further study of factors driving psychotropic medication use during pregnancy.

PHP9 - The Impact of Indication Extensions on Pharmaceutical Prices

To assess the impact of an indication extension on pharmaceutical prices in 9 markets: Australia, Brazil, France, Germany, Italy, Japan, Spain, Turkey, and the UK. Websites of the EMA and national regulatory agencies were surveyed to indentify medicines granted an indication extension between 2007 and 2013. Eight case studies (bevacizumab, trastuzumab, sunitinib, ivabradine, telmisartan, aripiprazole, paliperidone, and omalizumab) were selected based on market share and availability across the geographies of interest. The list prices, at ex-manufacturer levels, of these eight drugs and those of the medicines belonging to their therapeutic class (at ATC level 3) were collected for the period 2007-13. Price movements for these eight medicines were compared to the price evolution within their therapeutic class over the period. Based on the selected case studies, there is ambivalent synchrony between indication extensions and pharmaceutical list price movements in the countries analysed. The data show that list prices tend to remain stable following an indication extension. When list prices changed subsequent to an indication extension, the movements could not directly be linked to the indication extension, as external factors such as a class trend or a wider pricing and reimbursement process (e.g. blanket price cuts) could also play a role. There is inconclusive evidence that indication extensions lead to list price changes in the countries analysed. Moreover, the impact of commercial agreements and discounts should be taken into account as secondary indications may be subject to separate pricing arrangements (e.g., patient access schemes). As such, the selection of the indication for the first marketing-authorisation filing (such as a high medical need, niche indication, commanding a premium price) is pivotal for the commercial success of a medicine, as its launch price seems unlikely to be reviewed following subsequent approvals in broader patient populations.

Drug substitution associated with a hospital stay in Belgium: a retrospective analysis of a claims database

This study measures the extent of drug substitution associated with a hospital stay in Belgium. Data were extracted from the 2006-2007 dataset of the Belgian Agency of Health Insurance Funds on drug use of patients hospitalized in acute hospitals. Reimbursed drugs received in ambulatory care during the 3 months prior to hospitalization were compared with drugs received during the 3 months following hospital discharge. Both a narrow definition and a broad definition were used for drug substitution. Narrow substitution (switches between generic and originator drugs) was computed for 14 drug classes for chronic conditions with the highest public expenditure. Broad substitution (changes between chemical substances within the drug class at ATC level 4, changes in brand name) was calculated for statins and proton-pump inhibitors only. The database included 17 764 patients (mean age 66 ± 17 years; 60% female). In 71% of cases an originator drug was received prior to and following hospitalization. A generic drug was received prior to and following hospitalization in 25% of cases. Some form of narrow substitution occurred in 4% of cases: a generic drug was replaced by an originator drug in 2% of cases and an originator drug was replaced by a generic drug in 2% of cases. Some form of broad substitution occurred in 25% of cases for proton-pump inhibitors and 13% of cases for statins. Hospitalization was not a trigger for changes between originator and generic versions of a drug. Broad substitution associated with a hospital stay was relatively limited for statins and proton-pump inhibitors.

PCV26 Real World Add-On and Switch Patterns for Platelet Aggregation Inhibitors

To analyze the add-on and switch patterns for patients who dispensed platelet aggregation inhibitors, excluding heparin (acetylsalicylic acid, clopidogrel, and dipyridamole) in the South-West region of Sweden. This was a retrospective database study of medication utilization amongst patients from the South-West region of Sweden (1.5 million inhabitants). All patients who dispensed platelet aggregation inhibitors (B01AC), excluding heparin, from 2006 to 2009 were included in the study. A dispatch was classified as new, switch, add-on, or continuation. All dispatches were annotated, at the ATC level, as either new (no other anticoagulant within 105 days), add-on (another anticoagulant dispatched both before and after), switch (another anticoagulant dispatched before, but not after), or continuation (dispatched same ATC-code within 105 days). 163 330 patients had at least one B01AC filled prescription. The total number of dispatches for these patients were 3 327 499. 96% of all patients had been dispatched acetylsalicylic acid (ASA), 11% clopidogrel and 6% dipyridamole. ASA was dispatched as a new prescription in 17% of all dispatches, in <0.5% as add-on, <0.5% as switch, and in 83% as continuation. For clopidogrel the distribution was 17% (new), 4% (add-on), 3% (switch), and 77% (continuation). For dipyridamole the distribution was 7%, 18%, 8%, and 68%. Not surprisingly ASA was by far the most common treatment. ASA and Clopidogrel both had first line treatment profiles, of which it was most pronounced for ASA (<1% add-on or switch). Dipyridamole is used more as an add-on or switch therapy with 18% as add-on, 8% as switch, and only 7% as new dispatches.