FormalPara Key Points

The prevalence of potential drug duplications (DDs) has almost doubled in older adults with ordinary prescriptions from 2006 to 2021.

The drug groups most frequently implicated in the DDs were cardiovascular drugs, vitamin B12 and folic acid, and drugs for peptic ulcer and gastroesophageal reflux disease.

As DD may increase the risk of adverse drug reactions, more national efforts are needed to revert this trend, including a nationally available complete drug list for all patients, and prescriber support to detect DDs.

1 Introduction

Drug duplication (DD), defined as the concurrent use of two drugs with the same active ingredient(s), is an underrecognized medication error increasing the risk of overdose and adverse effects [1]. The dose increase associated with unintended DDs may be specifically harmful to older adults, being more sensitive to high drug concentrations [2]. This might contribute to the already high overall risk of adverse drug reactions (ADRs) in older adults, resulting in morbidity, hospitalization, healthcare costs, and mortality [3]. DDs have been reported to be more common among older adults with polypharmacy (usually defined as the concurrent use of five or more drugs) and among persons with more than one prescriber [1, 4]. Given that the prevalence of polypharmacy has been reported to be on the rise [5, 6], it is of great importance to also monitor trends in DD and the specific drugs implicated.

DD can occur for a number of reasons, including automatic generic substitution (substitution to the cheapest brand with the same active ingredient), multiple prescribers, shortcomings of electronic prescription systems and multiple sources of medication lists [7]. Compared with therapeutic duplications (concurrent use of drugs in the same class), DDs are more often unintended and inappropriate. However, as noted in previous studies of duplicate drugs using routinely collected data, it is difficult to distinguish between stockpiling and duplicate use when only dispensing records are available and not data on actual consumption [1].

Previous research has shown that the prevalence of DD is high among older adults. For example, a study in the UK reported a high baseline prevalence of DD (9%) in patients treated in general surgical wards, indicating the widespread occurrence of this phenomenon even among non-older populations [8]. In ambulatory care settings, a study using Korean national health insurance claims data found that DD was more frequent for antihypertensives and lipid-modifying drugs, both within and between prescriptions [9]. A study in Italy found that the prevalence of patients exposed to at least one DD increased significantly from hospital admission to discharge, and the majority of patients discharged with duplicate drugs were still taking them at a 3-month follow-up [10].

In Sweden, previous studies have reported a relatively high prevalence of DD in older patients with chronic conditions. For instance, a report on drug utilization reviews in ambulatory older patients in Sweden during 2007–2008 reported therapeutic duplication (use of two or more drugs with similar pharmacodynamic properties) as high as 13% in individuals aged 65 years and older [11]. Another study based on electronic data in patients with diabetes mellitus, congestive heart failure, or osteoarthritis found a prevalence of DD of 4.9% in the medication list in the electronic medical record and 6.1% in the list stored in the national prescription repository [12]. A more recent Swedish study reported a prevalence of 9.3% for DD [7], suggesting that DD is a prevalent issue.

Despite the previous findings of a high prevalence of DD in older adults, there is a lack of research investigating time trends in DD in Sweden and elsewhere. This is of particular interest considering the continuously increasing drug use in older adults [5, 6]. Therefore, the primary aim of this study was to investigate trends in potential DD in older adults in Sweden from 2006 to 2021. Additionally, this study aimed to report the drug groups that are most frequently implicated in these DDs.

2 Methods

We used routinely collected administrative prescription data with national coverage, from the Swedish National Prescribed Drug Register (SPDR), for the years 2006, 2011, 2016, and 2021. The SPDR contains extensive information on all prescribed medications dispensed at a pharmacy for the whole Swedish population.

2.1 Study Design and Population

In this repeated cross-sectional study, we included older adults (age ≥65 years) with ‘ordinary’ drug prescriptions, i.e. drugs dispensed at community pharmacies, during the study years. We excluded persons with multidose dispensing each year, since multidose dispensations typically are delivered regularly every 2 weeks, and therefore the likelihood of finding DDs according to the present definition would be very low. The number of excluded multidose users was 152,937 in 2006, 187,652 in 2011, 221,097 in 2016, and 283,622 in 2021.

2.2 Drug Exposure

For each person, information on all drugs dispensed during the year was collected. Drug exposure windows for each dispensation was calculated from the dispensing date to the date when the supply of the drug ended. The end date was calculated by dividing the amount of drug dispensed by the prescribed daily dose (available in free text), which gives an assumed number of days that given drug dispensation should last, and then adding this number to the dispensing date, as previously described [13].

2.3 Duplicate Drugs

DD was defined as the dispensations of two or more drugs with the same active substance (7-character, 5th level, Anatomical Therapeutic Chemical [ATC] code) but with different brand names, overlapping for 30 days or more during a 3-month period (October–December) each year. DD consisting of at least one drug for external use (ointments, mouthwash, etc.) or for as-needed use were excluded due to difficulty in estimating the correct daily dose and thus the end date of the medication. Drugs for injection were also excluded from the analysis, as it is likely that a DD with drugs for both oral and parenteral administration is either intentional or the result of clinically justifiable switches.

Sex and age (categorized into 65–79 years and ≥80 years) was extracted from the SPDR.

2.4 Statistical Analysis

The prevalence of DD was calculated each year by dividing the number of individuals with duplicated drugs by the number of persons with at least one ordinary drug dispensation estimated to be in use during October–December each year. Descriptive statistics, including proportions (%), mean, standard deviation, median and interquartile range (IQR), were calculated using SPSS 26.0 (IBM Corporation, Armonk, NY, USA).

3 Results

The study populations consisted of more than 1 million individuals each study year with filled ordinary prescriptions estimated to be in use October–December each year. The populations included more women than men. The average number of used drugs increased over the 15 years from 2006 to 2021 (Table 1).

Table 1 Description of the study populations 2006, 2011, 2016 and 2021, divided by age
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The overall prevalence of potential DD increased from 5.8% in 2006 to 10.9% in 2021. The increasing trend was observable in both women and men, and in both age groups (Figs. 1a, b). Men showed a slightly higher prevalence of DD compared with women, and persons ≥80 years of age showed a higher prevalence than those aged 65–79 years.

Fig. 1
figure 1

Prevalence of duplicate drug use in men (blue bars) and women (orange bars) in 2006, 2011, 2016 and 2021. a 65–79 years of age; b ≥80 years of age

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The top five drug classes (ATC level 3; pharmacological subgroup) implicated in the potential DD are shown in Table 2. Vitamin B12 and folic acid (ATC: B03B) and β-blocking agents (C07A) were among the top five drug groups for all 4 years. Lipid-modifying agents (C10A) in 3 of 4 years, and drugs for peptic ulcer and gastroesophageal reflux disease (A02B; mainly consisting of proton pump inhibitors [PPIs]), high-ceiling diuretics (C03C) and angiotensin II receptor blockers (C09C) were among the top five drug groups in 2 years. At the substance level, metoprolol and bisoprolol were the most common duplicated drugs from the β-blocking agent group. It can also be noted that the antithrombotic agents, being more common among the DDs in 2021, mainly consisted of acetylsalicylic acid, although clopidogrel was nearly as frequent.

Table 2 Prevalence (%) of drug duplications at the pharmacological subgroup and substance level, in 2006, 2011, 2016 and 2021
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3.1 Subgroup Analyses

The drug groups most implicated in the potential DD were also analyzed separately for women and men (electronic supplementary material [ESM] Table S1) and for those aged 65–79 years and ≥80 years (ESM Table S2). The differences between men and women were small in all study years. For persons ≥80 years of age, high-ceiling diuretics (C03C) were more often implicated in DD, as compared with 65- to 79-year-olds.

4 Discussion

In this register-based study, we report that the prevalence of potential DD has almost doubled from 2006 to 2021 among older adults with ordinary prescriptions in Sweden, with a similar trend across age groups and sex. As a whole, more than 1 in 10 individuals had a DD during the three observed months in 2021. The drug groups (ATC level 3; pharmacological subgroup) most frequently implicated in the DD were overall cardiovascular drugs, vitamin B12 and folic acid, and drugs for peptic ulcer and gastroesophageal reflux disease, and, in 2021, additionally antithrombotics. National efforts are needed to revert this concerning trend.

Relatively few studies have investigated the prevalence of DD at the substance level, defined by the WHO as ‘double medication’ or ‘ingredient duplication’. To our knowledge, this is the first study reporting time trends at a national level. In a Swedish study from 2010 in which Ekedahl et al. [12] examined the discrepancies between the currently prescribed treatment stated by patients, the medication list from the electronic medical record, and the list stored in the national prescription repository, they found a prevalence of DD between 4.9% and 6.1% of all prescriptions. Using a similar methodology, a more recent Swedish study reported the prevalence to be 9.3% [7], which aligns with our results of an increasing trend. Ekedahl et al. also observed that duplicate drugs were more frequent in patients with congestive heart failure, compared with patients with diabetes mellitus or osteoarthritis [12]. This is in line with our findings that cardiovascular drugs are often implicated in DD. Thus, overall, our results are in accordance with previous findings in Sweden.

Our findings are also compatible with the international literature. Using claims data, a Korean study in an ambulatory care setting reported that the most frequently implicated drugs in DD were drugs for acid-related disorder [such as PPIs] (8%), antihypertensives (10%) and lipid-modifying drugs (9%) [9]. These three drug groups were also among the top five groups in our present study. There is high agreement between the most frequently used drugs among persons with polypharmacy in Sweden [14] and the most frequently duplicated drugs in our study. Hence, the drugs implicated in duplications seem to reflect frequency of use rather than any specific clinical consideration. This is also reflected by the higher proportion of duplicated diuretics in the older age group, as diuretics are used more frequently by the oldest segment of the population [14, 15]. Furthermore, we found only small sex differences in the prevalence of DDs, as has been reported by others [16].

Interestingly, our results showed a continuous increase in the prevalence of DD after 2006. This may reflect that new rules for generic substitution were introduced for Swedish pharmacies in 2009, stating that the cheapest exchangeable drug every month should be the first choice when dispensing prescriptions. This effectively means that a prescribed drug can be replaced each time the patient picks it up at the pharmacy. Unsurprisingly, lack of familiarity is a frequent reason for refusing substitution [17]. Given the high level of complexity in medication use for older adults with polypharmacy, adding regular switches in brand name and layout of packages might increase complexity further and increase the risk of medication errors, including DD.

Besides being irrational and unnecessary, a DD may lead to an overdose of the involved active substance(s), which in turn can result in ADRs, particularly in older persons where pharmacokinetic and pharmacodynamic changes increase the sensitivity to drugs [2]. Indeed, according to data from the Swedish suspected adverse reaction database (Swedish Medical Products Agency), connected to the European EudraVigilance system [18], several of the drug groups and substances that we found to be involved in the potential DD in the present study are prone to cause an ADR. In 2006, angiotensin-converting enzyme (ACE) inhibitors and β-blocking agents were the third and seventh most common drug groups reported to cause serious ADRs in older adults (≥65 years). In 2019, antithrombotic agents were the most common, and lipid-modifying agents the fifth most common, drug group in these ADR reports [19].

In clinical practice, the most important measures to avoid duplicate drugs is to maintain a comprehensive record of all medications the person is taking and to regularly conduct medication reviews (potentially using electronic systems with built-in alerts for duplicate therapies). A major challenge is when physicians cannot see all the medications a patient is prescribed. Many older adults have medications from more than one prescriber, potentially recorded in different systems. Thus, DDs may not be detectable for any of the prescribers. In Sweden, the development of a National Drug List (‘Nationella läkemedelslistan’) is ongoing [20]. Moreover, pharmacists in Sweden have had access to an electronic system called EES (Electronic Expert Support) since 2009 [21]. This system signals for a variety of different potential drug-related problems (DRPs), including potential DD. In an open controlled study, Danish et al. compared the rate of identification of DRPs for prescriptions dispensed by pharmacists with and without the use of EES [22]. A higher number of DRPs were identified with (n = 52) than without (n = 39) the support from EES. The most identified DRP was DD, although it was found to be detected to a lesser extent in the EES support group (10 instances) compared with the control group (15 instances). A national drug list coupled with EES might revert the increasing trend in DD; however, uptake of the EES system has been stated to be low and only used on about 20% of patients [22]. Increased awareness of the issue of DD is needed.

4.1 Strengths and Limitations

To the best of our knowledge, this is the first study to assess trends in DD in Sweden using nationwide register data. An important strength of the study is that it is based on all persons in Sweden aged 65 years and older using drugs with ordinary prescriptions. Moreover, it covers a long period of time, from 2006 to 2021, which allows examination of longer time trends in the prevalence and nature of DDs. However, there are also limitations. One is that the SPDR does not include over-the-counter (OTC) medications or drugs distributed within hospitals or dispensed from storerooms in nursing homes, which may have led to an underestimation of the prevalence of DD. Another limitation is that we do not know to what extent the studied patients are adherent to the drug prescriptions. However, we do at least know that they have picked up the medicines at the pharmacy. Finally, our calculation of the occurrence of potential DD cannot be equated with the true prevalence of DD, as some patients, or people who assist them with the drug management, might be aware that a drug is duplicated and hence avoid this error. However, it is reasonable to assume that an overlap of 30 days or more, of drugs with the same active substance but with different drug names, is highly indicative of duplicate drug use. Moreover, our measure of DD only includes overlap of medications with different brand names. Drugs with the same brand name can also be duplicated; hence, we have chosen a conservative measure of DD.

5 Conclusion

In this study, we demonstrated that the prevalence of potential DD has almost doubled in older adults with ordinary prescriptions during the last two decades, reaching 11% in 2021. In general, we found that the drugs that are most frequently duplicated tend to mirror the most used drugs in the older population. DD is a potentially hazardous medication error that can be avoided. The rising prevalence of DD suggests that more national efforts are needed to revert this trend, including a nationally available complete drug list for all patients, increased awareness, and prescriber support to detect DD.