Search

Purpose: The aim of the present paper is to study which prescription pain medications are most commonly dispensed to people with chronic headache (CH), particularly those with medication-overuse headache (MOH). Methods: This cross-sectional study analysed prescription pain medications dispensed within 1 year to 68,518 respondents of a national health survey. Participants with headache ≥15 days per month for 3 months were classified as having CH. Those with CH and over-the-counter analgesic use ≥15 days per month or purchase of ≥20 or ≥30 defined daily doses (DDDs) of prescription pain medication per month (depending on the drug) were classified as having MOH. Associations between CH and other chronic pain conditions were analysed by logistic regression. Results: Among those with CH (adjusted prevalence 3.3 %, CI 3.2-3.5 %), pain medications most commonly dispensed were paracetamol, tramadol, ibuprofen and codeine. CH was associated with osteoarthritis, back pain, and rheumatoid arthritis. Among those with MOH, 32.4 % were dispensed an opioid at least once within 1 year. Only 5.1 % of people with CH were dispensed triptans. Conclusions: High prevalence of opioid use among people with CH may be due to inappropriate headache treatment or development of MOH among those treated for other pain conditions. While there were cases of triptan overuse, triptans remain underutilized among those with CH, suggesting that migraine may be under-recognized and inappropriately treated, leading to overuse of other medications. Education of physicians on appropriate headache management is essential for MOH prevention. There is a need to increase universal awareness about MOH as an adverse effect of long-term analgesic use. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries. Methods: Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions (2018 vs. 2010). Results: Prevalence proportion of statins increased from 24.8% to 24.6% (UK), 21.0% to 22.3% (Region of Southern Denmark [RSD]), 12.9% to 14.3% (Udine, Italy), and 20.3% to 23.2% (Spain). Prevalence proportions of antithrombotics declined in all four countries: 18.7% to 15.9% (UK; − 2.8% points), 18.9% to 18.1% (RSD; − 0.8% points), 17.7% to 16.6% (Udine; − 1.1% points) and 15.0% to 13.6% (Spain; − 1.4% points). These declines were driven by reductions in low-dose aspirin use: 15.3% to 8.9% (UK; − 6.4% points), 16.3% to 9.5% (RSD; − 6.8% points), 13.5% to 11.6% (Udine; − 1.9% points), and 10.2% to 8.8% (Spain; − 1.4% points). In the UK, low-dose aspirin use declined from 9.1% to 4.3% (− 4.8% points) for primary CVD prevention, and from 49.6% to 36.9% (− 12.7% points) for secondary prevention. Oral anticoagulant use gradually increased but did not fully account for the decrease in low-dose aspirin use. Conclusions: Antithrombotic use in the UK, RSD, Udine and Spain declined between 2010 and 2018, driven by a reduction in use of low-dose aspirin that is not completely explained by a gradual increase in OAC use. Use of statins remained constant in the UK, and increased gradually in the RSD, Udine and Spain. [ABSTRACT FROM AUTHOR]

Purpose: A rapidly increasing use of biological drugs has led to substantial costs. Shift to biosimilars enables considerable reduction of these costs without jeopardizing the treatment of patients, but most countries have extensive possibilities of untapped cost-savings. The aim of this study was to describe the Danish quick and near-complete implementation of the two first TNF inhibitor biosimilars (infliximab and etanercept). Methods: We shed light on the considerations and experiences made during the implementation, and present key figures from the implementation. Results: The infliximab biosimilar constituted 90.6% of the total amount of infliximab four months following patent expiration of the biooriginator. Similar results were seen for etanercept biosimilar. Substantial cost reductions were experienced in the way that e.g. the infliximab-shift reduced cost by two thirds. Conclusion: We believe that a thorough preparation and an organizational setting supporting the implementation is crucial for the successful implementation. This same implementation model will be used for future biosimilars. [ABSTRACT FROM AUTHOR]

Purpose: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. Methods: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. Results: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). Conclusions: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile. [ABSTRACT FROM AUTHOR]

Purpose: Montelukast is a leukotriene receptor antagonist used in asthma and rhinitis treatment. Despite being marketed nearly two decades ago, little is known about its utilisation pattern. Methods: Using the Danish National Prescription Registry, we identified subjects filling a montelukast prescription between 1998 and 2017. Using descriptive statistics, we reported the development in incidence, and prevalence, as well as a measure of treatment duration, and concomitant use of asthma- or anti-allergic therapy. Results: We identified 147,247 individuals filling 1,327,489 montelukast prescriptions. A total of 54,349 users (37%) filled only one montelukast prescription. The prevalence increased from 0.9/1000 persons in 1998 to 3.3/1000 persons in 2016. The rate of new users reached its maximum of 2.1/1000 person-years in 2009. Among new montelukast users, 28% were still users after 1 year. Among all montelukast initiators, 60% filled at least one prescription of short-acting beta-2-agonists (SABA) up to a year prior to montelukast initiation, and 49% filled a prescription of inhaled corticosteroids (ICS). Only 0.8% ( n = 1148) of all individuals initiated montelukast without a redeemed prescription of short- or long-term inhalation therapy, systemic antihistamines, or nasal topical anti-allergic treatment. Conclusions: The usage of montelukast has increased over threefold since its market entry in 1998, mainly driven by an increased number of prevalent users. The majority of individuals who initiated montelukast filled a prescription of SABA up to a year prior to montelukast initiation, whereas almost half filled a prescription of ICS. [ABSTRACT FROM AUTHOR]

Aims: We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors. Methods: We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC). We categorized the place where the error occurred, the processes and types of error involved, the person responsible, and the clinical outcome. Results: We identified 173 errors. In 109 (63 %), either harm resulted or could not be excluded; of these, 26 (15 %) resulted in serious harm, including nine deaths (5 %); 53 (31 %) involved incorrect daily administration; and 107 (62 %) involved a dosing error. Sixteen events (9.2 %) concerned insufficient or faulty monitoring, with four serious outcomes and two deaths. Prescription errors involving daily rather than weekly administration, by hospital physicians, were most likely to result in serious outcomes, including deaths. The error mechanism was evaluated in 129 events. Action-based errors comprised 50 % and knowledge-based errors 34 %. Action-based errors were more likely to result in completed errors, whereas knowledge-based errors more often resulted in near misses. Conclusions: The medication errors in this survey were most often action-based (50 %) and knowledge-based (34 %), suggesting that greater attention should be paid to education and surveillance of medical personnel who prescribe and monitor methotrexate, particularly physicians, who accounted for 40 % of the errors. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe primary non-adherence (PNA) in a Danish general practitioner (GP) setting, i.e. the extent to which patients fail to fill the first prescription for a new drug. We also assessed the length of time between the issuing of a prescription by the GP and the dispensing of the drug by the pharmacist. Lastly, we sought to identify associations between PNA and the characteristics of the patient, the drug and the GP. Methods: By linking data on issued prescriptions compiled in the Danish General Practice Database with data on redeemed prescriptions contained in the Danish National Prescription Registry, we calculated the rate of PNA among Danish patients from January 2011 through to August 2012. Characteristics associated with PNA were analysed using a mixed effects logistic regression model. Results: A total of 146,959 unique patients were started on 307,678 new treatments during the study period. The overall rate of PNA was 9.3 %, but it varied according to the major groups of the Anatomical Therapeutic Chemical (ATC) Classification System, ranging from 16.9 % for 'Blood and bloodforming organs' (ATC group B) to 4.7 % for 'Cardiovascular system' (ATC group C). Most of the patients redeemed their prescriptions within the first week. Older age, high income and a diagnosis of chronic obstructive pulmonary disease were found to be significantly associated with lower rates of PNA, while polypharmacy and a diagnosis of ischaemic heart disease were associated with higher rates of PNA. Conclusions: The overall rate of PNA among Danish residents in a GP setting was 9.3 %. Certain drug classes and patient characteristics were associated with PNA. [ABSTRACT FROM AUTHOR]

Purpose: This nationwide study is aimed at describing to what extent the European Paediatric Regulation has met therapeutic needs in children. Methods: Data for each drug substance in defined daily doses (DDD) were extracted from the national Danish data base. We evaluated if drug substances were used off-label and whether they had a paediatric investigation plan (PIP). This study did not include drug prescriptions for individual paediatric patients; thus, it was not possible to make use of all off-label categories previously used. Additionally, paediatric standard assortments (SA) were compared to the European survey on paediatric medicinal products. Results: Thirteen percent of the 100 most used drug substances were determined as being used off-label, four of which had a PIP and one had a full waiver. Only one of the three drug substances used off-label most often, accounting for 85 % of such use, had a PIP. Neonates were included in one-third of PIPs and adolescents in 15. Nineteen out of 21 PIPs had a waiver and 14 PIPs were deferred. In line with the European survey, carbapenems, corticosteroids and proton pump inhibitors were frequent found in SAs. Conclusion: PIPs only cover a small proportion of the drugs found to be used off-label in this study. Despite waivers granted, drug substances were used nonetheless. Unmet regulatory needs are still considerable in some therapeutic areas in neonates as well as in children. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to characterise the utilization of the glucagon-like peptide-1 (GLP-1) analogues exenatide and liraglutide in Denmark. Methods: From the Danish National Prescription Registry, we extracted all prescriptions for either liraglutide or exenatide twice-daily in the period 1 April 2007 to 31 December 2012. Using descriptive statistics, we calculated incidence rates, prevalence proportions, daily consumption, and concomitant drug use. For a subset of users we included data from other registries and characterised the baseline characteristics of incident users of GLP-1 analogues. Results: We identified 21,561 and 2,354 users of liraglutide and exenatide respectively. From market entry in 2009 liraglutide showed an increasing prevalence reaching 2.4 per thousand inhabitants in 2012. Exenatide ranged between 0.01 and 0.25 per thousand inhabitants from 2007 to 2012. Treatment intensity showed geographical variation ranging from 1.84per thousand inhabitants to 3.22 per thousand inhabitants for liraglutide. Average doses were 1.34 mg/day (liraglutide) and 16.4 μg/day (exenatide). Treatment initiation was most often performed by a hospital physician and was not associated with any changes in concomitant treatment with antihypertensives, cholesterol-lowering drugs or anticoagulants. Of liraglutide and exenatide users, 38 % and 43 % also used insulin. Low kidney function (eGFR < 30 ml/min) was found in 10.1 % and 9.0 % of users of liraglutide and exenatide respectively. Conclusions: The preferred GLP-1 analogue in Denmark is liraglutide. Certain aspects of the utilization of GLP-1 analogues, such as large regional differences and concomitant use of GLP-1 analogues and insulin, warrant further investigation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether general practitioners, hospital physicians and specialized practitioners in psychiatry have similar preferences for initiating treatment with expensive serotonin-specific reuptake inhibitors (SSRIs). Methods: All first-time prescriptions for the SSRIs escitalopram, citalopram and sertraline reported to the Danish National Register of Medicinal Product Statistics from April 1, 2009 until March 31, 2010 were analysed with regard to treatment naivety and type of prescriber. A prescription was considered as first time if the patient had not received a prescription for the same drug within the last 2 years. Patients who had not received a prescription for an antidepressant within 6 months prior to the date of redemption were classified as treatment-naïve. Results: We included 82,702 first-time prescriptions, 65,313 (79 %) of which were for treatment-naïve patients. Of the treatment-naïve patients, 19 % were initially prescribed escitalopram. Hospital physicians prescribed escitalopram to 34 % of their treatment-naïve patients, while practitioners specialized in psychiatry prescribed it to 25 %, and general practitioners prescribed it to 17 %. General practitioners, however, were responsible for initiating 87 % of all treatment-naïve patients. Conclusion: The most expensive SSRI, escitalopram, is prescribed as first choice to one in five patients receiving their first antidepressant of escitalopram, citalopram or sertraline. General practitioners made the bulk of all first-time SSRI prescriptions to treatment-naïve patients. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to characterize utilization patterns for drugs used to treat attention deficit/hyperactivity disorder (ADHD) on the level of the individual patient among Danish users, focusing on treatment duration, doses used, and concurrent use of ADHD and non-ADHD drugs. Methods: Using the Danish Registry of Medicinal Product Statistics, we extracted data on 1,085,099 prescriptions for ADHD drugs issued to a total of 54,024 persons in the study period 1 January 1995 to 30 September 2011. For users in the final year of the study period, we further extracted 315,365 prescriptions for non-ADHD drugs. Drug utilization was characterized using descriptive statistics. Results: The mean duration of ADHD treatment was highest (3.6-4.2 years) for patients initiating therapy at a young age (age<13). Dropout rate after receiving only one prescription was highest among off-label users (age<6 and age >17). All age categories showed an increase in the average daily dosage of methylphenidate used from 2003 to 2010. Concomitant treatment with methylphenidate and atomoxetine was rare, as only 2 % of methylphenidate treatment overlapped with atomoxetine treatment. Nineteen percent of methylphenidate instant-release treatment overlapped with methylphenidate controlled-release treatment. Users of ADHD drugs across all age categories had an increased use of drugs related to the nervous system, especially antipsychotics [standardized morbidity rate (SMR), 6.4-19.5] and antiepileptics (SMR, 4.0-5.5). Conclusion: We found certain traits that warrant further investigation: the apparent increase in average daily doses, the low adherence to treatment among off-label users, and the increased use of other psychotropic medication. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study was to characterize the utilization of medication against attention deficit hyperactivity disorder (ADHD) in Denmark between 1995 and 2011 from a national perspective, by using population-based prescription data. Methods: National data on drug use in Denmark between 1 January 1995 and 30 September 2011 were extracted from the Registry of Medicinal Product Statistics (RMPS). Drug utilization was characterized using descriptive statistics. Results: A total of 1,085,090 prescriptions issued to 54,020 persons were identified. The incidence rate was stable in the last 3 years of the study period, and a slightly decreasing incidence rate and a stabilizing prevalence were observed towards the end of this period. The therapeutic intensity was 6.7 defined daily dose/person/day, with large regional differences that ranged from 64 to 145 % of the national average. Methylphenidate accounted for 92.6 % of DDDs used. The general practitioner (GP) rarely initiated treatment, although treatment initiation based on the GP's advice increased with older age of the patient. Maintenance treatment was found to be distributed roughly equally between prescriber types. For methylphenidate, 1 % of users accounted for 6.1 % of the drug volume and 50 % of users accounted for 84.4 %. The data therefore do not suggest a high proportion of heavy users. Conclusion: The findings of this analysis are mostly reassuring, with the data indicating a seemingly stagnant incidence and prevalence rate and lacking evidence of heavy users. However, the prescriber profile for incident users and the large regional variances raise concerns. It is therefore vital that the use of ADHD drugs is closely monitored. [ABSTRACT FROM AUTHOR]

Background: It is essential that pharmacies and prescribers have an overview of each patient's medication in order to prevent drug interactions, unintentional co-prescribing, unnecessary polypharmacy and underprescribing. We have assessed this overview by measuring the 'fidelity coefficient', a measure of the extent to which a drug user has a preference for one prescriber or one pharmacy. Methods and setting: Data for all prescriptions issued for the population in Southern Denmark (population 1.2 million) in 2009 was extracted from the Odense University Pharmacoepidemiological Database (OPED). Analysis of the extracted data was then limited to persons with at least ten prescriptions within the year, resulting in 8,246,064 prescriptions issued to 283,388 individuals. For each individual, we identified the most used prescriber and calculated the proportion of all prescriptions accounted for by that prescriber (FC). The individual user's most frequented pharmacy was also identified and the FC calculated in a similar fashion. Results: The average FC and average FC were 0.883 (standard deviation 0.158) and 0.927 (0.139), respectively. The estimated difference was 0.0446 (95% confidence interval 0.0439-0.0453). Among the factors associated with a high FC and high FC were older age, male gender and a high volume of prescriptions. The major drug classes that were most often prescribed by a non-main prescriber were beta-lactams, antidepressants and opioids. Similarly, the major drug classes associated with use of non-main pharmacy were beta-lactams, antidepressants and inhaled beta-agonists. Conclusion: Based on this analysis, both prescribers and pharmacies generally have an equal potential for maintaining an excellent overview of their patients' medication, but the pharmacies account for a slightly higher proportion of patients. [ABSTRACT FROM AUTHOR]

Purpose: There is no doubt that paediatric immunization prevents serious diseases, but the administration of these vaccines to healthy children also involves risks of adverse drug reactions (ADRs), some of which are potentially serious. The current body of evidence on ADRs from immunization therapy at the population level is partly contradictory across countries, time periods and childhood immunization programmes. The objective of our study was to characterize reported adverse events (AEFIs) following immunization in Danish children. Methods: Adverse events (AEFIs) in 0- to 17-year-old children and adolescents reported to the Danish Medicines Agency (DKMA) between 1998 and 2007 were analysed. The unit of analysis was one AEFI. Data were categorized with respect to time, age, and gender of the children, suspected vaccines, category and seriousness of the AEFIs, and reporting rate. Results: During the study period, the DKMA received 1,365 reports covering 2,600 AEFIs, corresponding to 60% of all adverse events reported for children. One third of the AEFIs were classified as serious, and two deaths were reported. The annual number of serious AEFIs remained constant during the study period. Approximately 80% of AEFIs were reported in children aged 0-2 years. Of all reported AEs, 45% were in the category 'general disorders and administration site conditions', followed by the categories 'skin and subcutaneous tissue disorders' (20% of total AEFIs) and 'nervous system disorders' (16% of total AEFIs). The largest share of serious events was from the category 'nervous system disorders' (33% of serious AEFIs). The most frequently reported serious AEs were febrile convulsions, pyrexia, and injection-site reactions. Conclusions: In Denmark, a large number of AEFIs following paediatric immunization have been reported, but the majority of cases were non-serious. [ABSTRACT FROM AUTHOR]

Objective: To analyse associations between indicators for adoption of new drugs and to test the hypothesis that physicians' early adoption of new drugs is a personal trait independent of drug groups. Methods: In a population-based cohort study using register data, we analysed the prescribing of new drugs by Danish general practitioners. Angiotensin-II antagonists, triptans, selective cyclo-oxygenase-2 antagonists and esomeprazol were used in the assessment. As indicators of new drug uptake, we used adoption time, cumulative incidence, preference proportion, incidence rate and prescription cost and volume. For each measure, we ranked the general practices. Ranks were pairwise plotted, and Pearson's correlation coefficient (r) was calculated. Next, we analysed the correlation between ranks across different drug classes. Results: For all indicators, the general practitioners' adoption of one group of drugs was poorly associated with adoption of others (r ≤ 0.49), indicating that early adoption of one type of drugs is not associated with early adoption of another. For all drug groups, adoption time adjusted for practice size was only weakly associated with other indicators (r: -0.56 to -0.27). Indicators, based on cost and volume of drugs, were highly correlated (r: 0.96-0.99), and the others correlated reasonably well (r: 0.51-0.91). Conclusions: Within drug groups, indicators of drug adoption, except for adoption time, correlate reasonably well. However, the theory that physicians' early adoption of new drugs is a personal trait independent of the type of drug could not be confirmed. The notion of the early-drug-adopting general practitioner may be mistaken. [ABSTRACT FROM AUTHOR]

Objective: The effect of lipid-lowering drugs (LLDs) on coronary heart disease is well established. However, their utilisation is often suspected to be too low. The aim of this study was to describe the epidemiology of LLD use with special emphasis on the development of utilisation over a 6-year period in a Danish population. Methods: For all people who purchased LLDs from 1993 to 1998 in Funen County, all prescriptions for LLDs and co-medication with cardiovascular and anti-diabetic drugs were retrieved from Odense University Pharmacoepidemiologic Database (OPED). Results: During the study period, LLD use increased nearly exponentially. In 1998, statins accounted for 95% of the total LLD consumption. The incidence increased markedly around the time of the publication of the Scandinavian Simvastatin Survival Study (4S). Only 3% of the statins were purchased without reimbursement. The female/male ratio was 0.69 and the median age was 60 years. General practitioners issued 73% of the total number of LLD prescriptions, and 55% of the treatments were initiated in general practice. A larger fraction of females and elderly started treatment in general practice. About 40% of the treatments were hospital initiated, and about one-third were followed up in general practice within the first year. Conclusions: Over the 6 years studied, utilisation of LLDs approached a level that may correspond to the current guideline recommendations. Compliance with guidelines should, however, be studied by following people with coronary heart disease. [ABSTRACT FROM AUTHOR]