*Article* **Medication Use and Storage, and Their Potential Risks in US Households**

**SuHak Lee \* and Jon C. Schommer**

College of Pharmacy, University of Minnesota, 308 Harvard Street, S.E., Minneapolis, MN 55455, USA; schom010@umn.edu

**\*** Correspondence: leex6829@umn.edu

**Abstract:** Background: Medications stored in US households may pose risks to vulnerable populations and the environment, potentially increasing societal costs. Research regarding these aspects is scant, and interventions like medication reuse may alleviate negative consequences. The purpose of this study was to describe medications stored in US households, gauge their potential risk to minors (under 18 years of age), pets, and the environment, and estimate potential costs of unused medications. Methods: A survey of 220 US Qualtrics panel members was completed regarding medications stored at home. Published literature guided data coding for risks to minors, pets, and the environment and for estimating potential costs of unused medications. Results: Of the 192 households who provided usable and complete data, 154 (80%) reported storing a medication at home. Most medications were taken daily for chronic diseases. The majority of households with residents or guests who are minors and those with pets reported storing medications with a high risk of poisoning in easily accessible areas such as counters. Regarding risk to the aquatic environment, 46% of the medications had published data regarding this risk. For those with published data, 42% presented a level of significant risk to the aquatic environment. Unused medications stored at home had an estimated potential cost of \$98 million at a national level. Implications/Conclusions: Medications stored at home may pose risks to vulnerable populations and the environment. More research regarding medications stored in households and their risks is required to develop innovative interventions such as medication reuse to prevent any potential harm.

**Keywords:** medication; storage; risk; reuse; household; inventory

#### **1. Introduction**

With the increasing use of prescription and over-the-counter (OTC) medications, more drug products are being accumulated in US households [1–14]. Larger medication inventories at home, and subsequent waste can endanger patient safety, reduce quality of care, and harm the environment. To develop interventions that efficiently mitigate unintended, negative consequences, there is a need to study medication use, storage, and disposal in households more in-depth and comprehensively. For instance, medication reuse pertains to redispensing of medications that were once acquired by an individual or healthcare facility. Redistributing unused medications can reduce healthcare waste and costs, and enhance access to care [15–22]. Patients are recognized as the primary consumers of reused medications and as one of the potential primary sources of medications to be reused [23–27]. Therefore, understanding the interplay between patients and their medications will clarify the types of risk that medication reuse can minimize, guide its efficient implementation, and illuminate its benefit. However, comprehensive research regarding the use, storage and disposal of their medications especially in the US is scant.

Accumulating medication inventories at home can harm patients and their families by increasing the risk of medication poisoning. Sorensen et al., found that the higher number of medications stored at home may increase the risk of taking someone else's medications

**Citation:** Lee, S.; Schommer, J.C. Medication Use and Storage, and Their Potential Risks in US Households. *Pharmacy* **2022**, *10*, 27. https://doi.org/10.3390/ pharmacy10010027

Academic Editor: Parastou Donyai

Received: 27 December 2021 Accepted: 2 February 2022 Published: 9 February 2022

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**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

within the same household [28]. According to the 2019 report of the American Association of Poison Control Center's National Poison Data System (NPDS), out of over two million reported exposure cases, 92.1% occurred in residence either of their own or someone else's. The poisoning of patients younger than 20 years of age comprised 57.5% of the reported exposure cases, so they seem to be particularly at higher risk than other age groups [29]. The NPDS reports from the previous years showed similar trends [30–33]. In addition to the high rate of occurrence, poisoning accidents of minors can cause injuries leading to emergency department visits and at times be fatal, but they are preventable and should be critically discussed [29–36].

Selective serotonin reuptake inhibitors (SSRIs), nonsteroidal inflammatory drugs (NSAIDs), acetaminophen (APAP), histamine-1 receptor antagonists (H1RAs), and sedatives/hypnotics/antipsychotics (SHAs) have been identified as medications commonly involved in child poisoning in the NPDS reports [12–14,28,29]. Opioids have also been identified as harmful and high-risk medications for poisoning of minors [35–45]. Regardless of the types of medications, the ease of access seems to play a significant role in pediatric exposure. For example, one survey that analyzed children who were poisoned by their grandparents' medications found medications stored in easily accessible locations such as shelves lower than three feet from the floor were significantly more involved in poisoning than those stored in high shelves [34]. Storing in closed spaces like drawers and closets would also provide additional physical barriers and keep medications away from children more effectively. Nevertheless, for opioids which are extremely habit forming, two studies found that 26% and 36% of the participants stored them in open spaces at home, respectively, noting unsafe storage of the high-risk medication [37,38].

The NPDS report also showed that 98.6% of all non-human exposures involved dogs or cats, implying that these household pets may be at risk of poisoning [29]. The NPDS reports did not specify the substances involved in these cases, but Cortinovis et al. comprehensively reviewed the drugs intended for human use that were frequently involved in poisoning of dogs and cats. Most medications of concern in the review were the same as the high-risk medications for humans, while some, such as vitamin D, iron salts, and β2-agonists seem to be high-risk more specifically for dogs and cats [46].

In addition to poisoning, accumulation of unused, unwanted, and expired (UUE) medications at home in the US has been frequently reported in the literature [13,14,37,39–43]. The accumulation of UUE medications may represent inefficient medication utilization and a potential source of financial waste in healthcare. The economical loss may not seem so apparent, as no significant difference in total prescription costs between those who had any unused medications and who did not was found [14]. However, these medications are stored without fulfilling their intended consumption goals. They can continuously require storage costs and hamper adequate access to medications for other potential purchasers that could have benefited from their use [47,48].

It is concerning when UUE medications are discarded in the end, especially because the most common locations of medication disposal were identified as garbage, toilet and sink in the literature [11,38,39,42]. These disposal methods are also recommended by the Food and Drug Administration (FDA) [49]. However, with these methods, pharmaceuticals still can be introduced into the water system and eventually into the groundwater, lakes, and streams, harming the environment and potentially humans [12,22,27,50–52]. Considering the negative implications, assessment of the potential environmental effects of medications stored at home is imperative. Such an assessment would reaffirm the significance of the environmental issues associated with these medications and help develop better disposal practices to minimize environmental harm.

The 2014–15 Environmentally Classified Pharmaceuticals report by the Stockholm County Council provides the most comprehensive assessment of various medications' environmental effects [53]. However, the evidence provided by the report was based on the Swedish water system and their standard medication doses, and may not be fully applicable in the US. Despite the shortcomings, no study has critically explored the potential

environmental risk of medications stored in US households. The Stockholm report can serve as a foundational reference for exploration and basic assessment of the potential risk.

Besides the different types of risk discussed above, the higher number of medications stored at home has been associated with deeper underlying issues with patients such as high severity of illness, therapeutic duplication, confusion between generic and trade names, low medication adherence and lack of medication administration routine [28]. Possessing unused medications also has been associated with a greater number of comorbidities, more frequent visits to emergency departments, primary care physicians, or specialists, and higher total medical cost of care [14]. Similar to these factors, polypharmacy, commonly defined as concurrent use of five or more medications, seems to be strongly associated with greater and unnecessary medication use [54]. The older population especially has a higher chance of comorbidity and is more likely to experience polypharmacy. Maneuvering through multiple, intricate medication therapies can be burdensome for many [54–58]. For this reason, when older patients manage their medications on their own, polypharmacy can arguably contribute to low medication adherence [59–61], potentially creating an unnecessary reservoir of medications stored at home.

Research assessing the aforementioned risks and economic implications of medications stored in the US households is scant. To fill the gaps in the literature, the first objective of the study was to describe medications stored in U.S. households including the number, indications, frequency of use, and storage locations. The second objective was to evaluate unintended consequences of these medications regarding (a) risk for poisoning of minors, (b) risk for poisoning of pets, and (c) risk to the environment. The third objective was to estimate the potential economic cost of the unused medications stored at home.

#### **2. Materials and Methods**

The 2018 National Household Medication Inventory Survey was the data source for this cross-sectional study. The survey was deemed to be non-human research and exempt from full review by the University of Minnesota Institutional Review Board. A total of 220 Qualtrics panel members in the U.S. were surveyed from May–June 2018. The Qualtrics Panel members who volunteered to participate in the survey received an invitation from Qualtrics, and the survey was self-administered. Upon completing the survey, each panel member earned credits which were reimbursed monetarily later. The overview of the data analysis is shown in Figure 1.


**Figure 1.** Study Overview ( a : prescription only, b : over-the-counter, c : serotonin reuptake inhibitors, d : nonsteroidal inflammatory drugs, e : acetaminophen, f : histamine-1 receptor antagonists, g : sedative/hypnotics/antipsychotics, h : persistence (P), bioaccumulation (B), and toxicity (T), i : calcium channel blockers).

#### *2.1. General Assessment of Households and Stored Medications*

#### 2.1.1. Household Analysis

In the survey, the participants were asked to choose from "0 medication," "1–4 medication(s)," "5–10 medications," or "more than 10 medications" for the number of medications stored by each household. The participants who reported storing no medication were asked to stop at the beginning of the survey without answering any subsequent questions about the household members.

The survey also assessed whether a household had a resident under 18 years old, a monthly guest under 18 years old, a resident older than 65 years old, and a pet. The Fisher's exact test was utilized to compare the number of medications stored by the households with at least one resident older than 65 years and those without.

#### 2.1.2. Medication Analysis

#### (a) Categorization of medications

The names of medications the participants stored in their households were reviewed and categorized by their prescription status (prescription, controlled substance, or OTC) and common indications. The controlled substance status was determined based on the Controlled Substances Act, following the federal classification. Medications like aspirin and omeprazole which can be available both as prescription and OTC, were categorized as OTC.

The typical indications of the reported medications were determined by the principal investigator (S.L.) who practices as a pharmacist in Minnesota, USA. The categorization of indications intended to be as inclusive as possible without having much overlap among the indications. A detailed description of the process of assigning medication indications is provided in Appendix A. A response with a typo that hindered interpretation of the exact name of the medication was categorized as "invalid." When the same medication was reported more than once by the same household, any responses reported subsequently to the first response were categorized as "duplicate."

#### (b) Medication frequency of use and storage locations

For the frequency of use of each medication, the participants were asked to choose from "taken daily," "taken as needed," "not taken, saving for future," "not taken, would like to discard," and "other." The participants were not given an option to specify "other." For the storage location of each medication, they were asked to choose from "bathroom counter," "bathroom cabinet," "garage," "kitchen counter," "kitchen cabinet or drawer," "utility room," "hallway closet," "bedroom counter," "bedroom cabinet," "bedroom closet," and "other." The participants were not asked to specify "other" in the survey.

#### *2.2. Potential Risk of Poisoning Analysis*

The risk analysis assessed whether high-risk medications for poisoning of minors and pets were stored on the counter by the households with a resident or monthly guest younger than 18 years old and a pet. Based on the literature, high-risk medications were determined as those more commonly involved in poisoning or associated with serious poisoning with harmful outcomes for minors and pets, particularly dogs and cats. The types of pets owned by the households were not asked in the survey, and it was assumed that the households owned either dogs or cats for simplicity and to adapt the findings of Cortinovis et al. [46].

The high-risk medications for minors included selective serotonin reuptake inhibitors (SSRIs), nonsteroidal inflammatory drugs (NSAIDs), acetaminophen (APAP), histamine-1 receptor antagonists (H1RAs), sedative/hypnotics/antipsychotics (SHAs), and opioids [29–33]. In the National Poison Data System (NPDS) reports, the SHA medications are comprised of barbiturates, atypical antipsychotics, benzodiazepines, buspirone, chloral hydrate, ethchlorvynol, meprobamate, methaqualone, phenothiazines, and histamine-related OTC sleep aids excluding diphenhydramine [29–33]. The high-risk medications for dogs and

cats included analgesics (NSAIDs and acetaminophen), antihistamines (diphenhydramine, doxylamine, hydroxyzine, loratadine), calcium channel blockers (CCBs), SSRIs, baclofen, sedative-hypnotic drugs such as benzodiazepines, and non-benzodiazepine hypnotic sedatives, loperamide, vitamin D, and β2-adrenergic receptor agonists [46].

#### *2.3. Potential Environmental Risk Analysis*

Based on the 2014–15 Environmentally Classified Pharmaceuticals published by the Stockholm County Council, each reported medication was assigned with a risk of toxicity to the aquatic environment and Persistence, Bioaccumulation, Toxicity (PBT) score. The persistence (P), bioaccumulation (B), and toxicity (T) of the PBT scores represent the ability to resist degradation in the aquatic environment, accumulation in adipose tissues of aquatic organisms, and the potential to poison aquatic organisms, respectively. Each characteristic is assigned a score ranging from 0–3, with a higher value indicating a higher risk. The sums of the scores of the three characteristics of medications have been reported as the PBD Index and utilized for the analysis in the current study [53].

The risk levels were classified as "insignificant," "low," "moderate," and "high." Medications that had undetermined risk levels due to insufficient evidence or were not mentioned in the report were categorized as "insufficient data." Vitamins, electrolytes, amino acids, peptides, proteins, carbohydrates, lipids, vaccines, and herbal medicine were not considered to pose a risk to the environment in the Stockholm report and were given the "exempt" status [53].

For combination medications whose active ingredients could be identified with the given response, the highest known risk level and highest known PBT score of the comprising ingredients were assigned. For example, when the comprising ingredients had both "insufficient data" and "insignificant" risk levels, the "insignificant" ingredient was determined to have more conclusive evidence for the risk and deemed the higher known risk level.

#### *2.4. Cost Analysis*

The potential cost of the medications that were reported to be either "not taken, saving for future" or "not taken, would like to discard" was assessed. The survey did not specify the units for quantities and strengths of medications to be reported for the participants. Without standardized units, the responses for quantities and strengths did not show a particular trend and could not be used for cost analysis. In order to estimate the potential cost, the sum of the lowest package Average Wholesale Price (AWP) on Red Book® for each medication regardless of the dosage form, strength, and package size was utilized [62]. The sum was then extrapolated to a national level, based on the US census data [63]. Utilizing the lowest unit AWP was considered, but it was suspected that the chance of storing multiple units of a medication would be higher than storing just one unit. Therefore, the next lowest cost estimate available which was the lowest package AWP at the time of the analysis in 2021 was utilized for the analysis.

Once the total potential cost of "not taken" medications was determined, the ratio of the number of US households based on the US census data (120,756,048 households) [63] and the number of households storing those medications was used to extrapolate the cost nationally.

The survey results were analyzed with Microsoft Excel 2016, SPSS (v. 27.0), and R (v.4.1.0).

#### **3. Results**

*3.1. General Assessment of Households and Stored Medications*

#### 3.1.1. Household Analysis

A total of 192 households (87.3%) out of the 220 households who volunteered to participate completed the survey. The zip codes of the participating households matched the geographic distribution of the US census data, indicating that the collected data were nationally representative [63]. The number of medications stored in the households is shown in Table 1. Note that 154 households (80.2%) reported storing at least one medication at home.

**Table 1.** Number of medications stored by households with at least one resident older than 65 years vs. without a resident older than 65 years.


<sup>a</sup> Fisher's exact test.

Forty-six households (24%) had at least one resident older than 65 years old (Table 1). The Fisher's exact test determined no significant difference in the number of medications reported by the households with a resident older than 65 years and the number reported by those without (*p* = 0.10).

#### 3.1.2. Medication Analysis

#### (a) Categorization of medications

A total of 457 medications stored at home were reported. After excluding eight "invalid" and 45 "duplicate" responses, a total of 404 valid responses were included in the analysis. Of the valid responses, 261 medications (64.6%) were prescription-only and 143 medications (35.4%) were OTC. Among the prescription-only medications, 25 medications (9.6%) were controlled substances. Table 2 has the breakdown of the indications of the reported prescription, controlled, and OTC medications. The three most commonly reported indications for prescription-only medications were cardiovascular therapy (33.5%), mental health therapy (18.6%), and endocrine therapy (16.5%). Mental health conditions (60%) such as attention deficit hyperactivity disorder (ADHD), and anxiety were the most commonly reported indications for controlled substances. The three most commonly reported indications for OTC medications were pain (37.1%), supplements (18.2%), and gastrointestinal therapy (13.3%) (Table 2). Among the households storing at least one medication at home, 72 households (46.7%) had at least one OTC medication stored at home. The crude responses for medication names are categorized by indications in Appendices B and E.

#### (b) Medication frequency of use and storage locations

Some of the responses for medication names categorized as "invalid" had their valid frequencies and locations reported. Also, a majority of the medications categorized as "duplicate" had different storage locations. For comprehensiveness, the frequency and location responses corresponding to "duplicate" or "invalid" in the medication indication analysis were included in the current analysis. The inclusion of these responses in the analysis yielded a total number of samples higher than the number of medications reported in the categorization.

A total of 465 responses for the frequency of use was collected. Table 3 shows most of the reported medications were being used: "taken daily," and "taken as needed" (93.8%).


**Table 2.** Indications of the medications stored in the households (*n* = 404 a ).

<sup>a</sup> "Invalid" and "duplicate" responses were excluded from the current analysis, b Includes indications with counts of 8 or fewer (complete counts provided in Appendix F), <sup>c</sup> Notably includes 9 benzodiazepines and 1 nonbenzodiazepine hypnotic sedative, <sup>d</sup> Notably includes 4 opioids and 1 neuropathic pain, e Includes indications with counts of 8 or fewer (complete counts provided in Appendix F).

**Table 3.** Medication frequency of use.


For storage locations, a total of 464 responses was collected. Most medications were stored in kitchens (31.9%), bathrooms (28.9%), and bedrooms (21.3%). A total of 147 medications (31.7%) were stored on open counters in bathrooms, kitchens, or bedrooms, which would be more accessible than those stored in drawers, closets, or cabinets (Figure 2). Two households submitted different numbers of responses for the frequencies and locations for their medications, and yielded different sample sizes (*n* = 465 vs. *n* = 464).

**Figure 2.** Medication storage locations (*n* = 464) \* Misc. in the x-axis includes 14 "utility room," 8 "garage," and 42 "other." The participants were not asked to specify "other" in the survey.

#### *3.2. Potential Risk of Poisoning Analysis*

Among households storing at least one medication (*n* = 154), 75 (39.1%) had at least one resident younger than 18 years old, 55 (28.6%) had at least one monthly guest younger than 18 years old, and 112 (58.3%) had at least one pet.

A total of five out of the six (83%) high-risk medications (all except opioids) was being stored on the counter by at least one household with one or more resident(s) younger than 18 years old. At least one household with one or more monthly guest(s) younger than 18 years old stored four out of the six (67%) high-risk medications (all except selective serotonin reuptake inhibitors (SSRIs) and opioids) on the counter. Of the nine high-risk medications, seven (78%) (all except vitamin D and baclofen) were being stored on the counter by at least one household with one or more pet(s). In fact, baclofen storage was not reported by any households with one or more pets.

#### *3.3. Potential Environmental Risk Analysis*

After excluding "duplicate" and "invalid" responses, a total of 404 valid medications reported in the survey were included in the environmental analysis and reviewed. Of the valid responses, six OTC medications had only their brand names reported, and were excluded from the current analyses. These brand medications are available in different variations of active ingredients, but the specific types were not reported in the survey. A total of 27 medications were "exempt" from the risk analysis per the 2014–15 Environmentally Classified Pharmaceuticals by the Stockholm County Council [53].

A majority of the medications, 53.9% and 60.1% of the medications did not have sufficient data to determine their risk of toxicity to the aquatic environment and their Persistence (P), Bioaccumulation (B), Toxicity (T) scores respectively (Figures 3 and 4). Among those with data, medications with insignificant-risk level (26.7%) were most prevalent (Figure 3). On the other hand, medications with PBT scores of 4 or higher (35%) were far more frequently identified compared to those with PBT scores lower than 4 (4.9%) (Figure 4).

**Figure 3.** Toxic risk levels assigned to the aquatic environment of the reported medications based on the 2014–15 Environmentally Classified Pharmaceuticals by the Stockholm County Council [53] (*n* = 371) \* "Insufficient data" includes medications with undetermined risk levels due to insufficient evidence or those that were not mentioned in the Stockholm report.

**Figure 4.** Persistence (P), Bioaccumulation (B), and Toxicity (T) scores of the reported medications. The PBT score is a sum of the P, B, and T score, each ranging from 0–3, assigned to a particular medication reported in the 2014–15 Environmentally Classified Pharmaceuticals by the Stockholm County Council. The higher the score, the higher the risk [53] (*n* = 371) \* Medications without a PBT score in the Stockholm report were categorized as "insufficient data.".

#### *3.4. Cost Analysis*

Out of the 19 "not taken, saving for future" or "not taken, would like to discard" responses, 14 had appropriately reported medication names. Based on the lowest package AWP, the 14 medications were worth \$156.54. Extrapolating this result to a national level, \$98,453,915.39 of medications were potentially stored at home without being used and potentially being wasted.

#### **4. Discussion**

#### *4.1. Objective #1: To Assess the US Household Members and the Number, Indications, Frequency of Use and Storage Locations of Their Medications Stored at Home*

Approximately 20% of the participating households did not store any medications at home. On the other hand, a household survey conducted in IL found all participating households storing at least one prescription or OTC medication at home [11]. No other US household surveys that could be used as a reference were identified during the literature review. Other similar studies assessed medication possession by individuals, not households.

The bivariate comparison of the number of medications between the households with and without any residents older than 65 found no statistical difference. However, the current survey did not collect the number of medications specifically stored by the individual residents older than 65, and the statistical analysis was explorative at best. The self-administered and online nature of the survey may have also heightened the barrier for the elderly to actively participate in the household survey.

The three most prevalent indications of the reported prescription medications were cardiovascular therapy, mental health, and endocrine therapy including diabetes. The Centers for Disease Control and Prevention (CDC) reported that 6 in 10 US adults suffer from chronic diseases including but not limited to the three identified in the current study. The most common indication of the reported OTC medications was "pain." This result may correspond to arthritis, another prevalent chronic disease reported by the CDC and often managed with analgesics. The prevalence of chronic diseases was also reflected in the most common medication frequency of use being "taken daily" [64–67].

Approximately a half of the households reported storing at least one OTC medication at home, consistent with the high prevalence of OTC medication use published in the literature. 8 of 10 US patients do not seek help from a healthcare professional initially for their minor illnesses and resort to OTC medications [9]. Considering the high barrier to healthcare access in the US, OTC treatment can be a convenient option for many patients.

Most medications reported in the study were stored in bedrooms, kitchen, and bathrooms. The alarming trend was a high number of medications being stored in bathrooms, which is inappropriate for medication storage. Funk et al. did a separate analysis for the appropriateness for each reported medication and their storage space, utilizing the published humidity and temperature ranges of various household locations and specific medication storage recommendations [68].

## *4.2. Objective #2: To Evaluate the Potential Risk for Poisoning of Minors and Pets and for the Environment Posed by the Medications Stored in the Study Households* 4.2.1. Poisoning Risk

A considerable amount (37.1%) of the reported medications were being stored on open counters in kitchens, bathrooms, and bedrooms. In addition, most of the high-risk medications for pediatric and adolescent poisoning were stored on counters by at least one household with a minor or pet. Counters are easily accessible and are not appropriate for medication storage, especially for households with vulnerable populations. In order to prevent and minimize harm by pediatric medication poisoning at home, the CDC recommends storing medications up and away and out of sight in a cabinet where a child cannot reach, never leaving medications unattended when a child is around, and having the Poison Help number readily available in the household [69]. It is uncertain whether patients living with minors or frequently having minor guests are educated about the importance of storage locations and how appropriately they store medications to prevent poisoning. As for pets, although only a small number of calcium channel blockers were reported, they have a small margin of safety, and ingestion of a small amount can be fatal for dogs and cats [46,70], and the pet owners should be appropriately educated.

Opioids were another type of high-risk medications reported in the literature. All the reported opioids in the study were not stored on a counter, suggesting that the study households were able to alleviate the risk of opioid poisoning and diversion to some degree. Locked spaces would be the optimal storage locations for opioids, but the survey did not assess whether the reported opioids were stored in locked spaces. Unlike the previous surveys with at least 30% of their samples having leftover opioids [37–43,71], the current study only had a small number of opioids reported. The discrepancy could also have been caused by inaccurate reporting or social desirability bias of the sample. The study sample might not have included a reasonable number of households with opioids and UUE medications in general.

#### 4.2.2. Environmental Risk

Almost a half of the reported medications had a Persistence, Bioaccumulation, Toxicity (PBT) score of 4 or higher, where a higher score indicated a higher environmental risk. In contrast, those with insignificant or low toxic risk to the aquatic environment combined took up a similar proportion. This finding highlights that medications without direct toxic effects on the aquatic environment can harm the environment via other mechanisms such as high persistence (P) and bioaccumulation (B). Despite the various ways of pharmaceuticals harming the environment, the literature found that up to 80% of the US patients are not educated about proper disposal methods of medications [11,37–39,42]. Additionally, the current disposal mechanisms and systems in the US have apparent limitations. The Resource Conservation and Recovery Act (RCRA) governs the framework for the generation, transportation, treatment, storage, and disposal of hazardous waste, but it recognizes only a small fraction of OTC medications as hazardous waste [52]. A new rule passed under RCRA in 2018 also set the threshold for pharmaceutical waste from healthcare facilities [72]. However, the rule seems to request the stakeholders to accomplish the set outcomes without providing sufficient support for achieving those goals. More efficient support can only be provided after more thoughtful consideration of the sources of pharmaceutical waste.

In addition to addressing the sources of the waste, the environmental effects of pharmaceutical substances need to be more extensively researched. In the current study, more than a half of the reported medications did not have any or enough environmental information available to determine their toxic risk to aquatic organisms or PBT score. The Stockholm report is the most comprehensive resource for the environmental effects of medications to this date, but it lacks considerable evidence and cannot be generalized to countries other than Sweden. PharmEcovigilance is a dimension of pharmacovigilance that governs the environmental effects of pharmaceuticals. The concept of pharmEcovigilance should be more actively promoted for accurate assessment of potential environmental risk and development of interventions protecting the environment from the potential harm [22]. Under this agenda, more pharmaceutical manufacturers should also be encouraged to research the environmental effects of their medications and share the findings with the public.

#### *4.3. Objective #3: To Calculate the Potential Cost of the Unused Medications or Medications Reported to Be "Not Taken" and Stored in the US Households*

The cost of the unused medications estimated based on the nationally representative sample was extrapolated to a national level, and the result was unremarkable. The national estimate reported by Law et al., was much higher than the estimate from the current study, ranging from \$2.4B to \$5.4B [13]. Their calculation may have overestimated the cost, as their data from the convenience samples were collected at drug-take-back events. At the same time, their estimate may be more accurate than the estimate of the current study, as they were able to tally the number of units and exact strengths of unused, unwanted and expired (UUE) medications collected from the sample. In spite of the deviation from the published estimate, the basic cost analysis of the current study would promote discussions about potential costs of UUE medications in the US.

Besides the apparent costs of the UUE pharmaceutical products, their invisible costs are equally concerning. When medications are stored at home, the transfer of medication inventories from suppliers to consumers incurs costs for acquisition and storage [47,48]. The limited access to healthcare in the US adds an additional cost to acquisition for most prescription medications. As for the storage costs, solid dosage medications may not take up a huge volume or require significant storage costs. However, liquid formulations such as insulin or biologics may require delicate storage conditions and additional storage costs. The storage costs can be further increased indirectly, considering the risk of harm via intentional or accidental poisoning or drug diversion, and its potential contribution to the total healthcare costs.

#### *4.4. Potential Solutions for Risk Mitigation*

Most existing interventions such as drug-take-back programs intend to minimize the environmental and poisoning risks by removing the unnecessary stocks stored at home. Their benefits have been studied mostly from an environmental perspective. Although any consolidated data regarding disposal methods of pharmaceutical waste in the US could not be identified during the literature review, most of the collected medications are suspected to be incinerated and contribute to more pollution [73]. On the other hand, medication reuse or drug repository programs may be a more environmentally friendly and economical alternative. As of 2018, 38 states and Guan in the US have enacted laws for medication donation and reuse, but about a third of them still do not have operational

programs. In order for medications to be donated, they have to meet multiple criteria including but not limited to being unexpired and unopened in their original, sealed, tamper-evident packaging, and having no signs of adulteration or misbranding. With the stringent provisions, the types of donors and medications are limited to certain oral medications [74,75]. These provisions are necessary as aligned with the general public concerns and perception about medication reuse [23,24,26,76], but innovative approaches such as packaging for pharmaceuticals, enhancing the quality and safety of medications and enabling their reuse are needed [77,78].

Despite the challenges, the medication reuse programs in the US have shown prospects for growth and benefit. Iowa and Wyoming reported their success in redistributing \$17.7 million and \$12.5 million worth of medications in one fiscal year, respectively [74]. The American Society of Clinical Oncology also publicly expressed its commitment to supporting drug repository programs in 2020. Although their support is only for redistribution of oral medications maintained in a controlled and supervised healthcare environment, this may indicate that more sectors within healthcare are recognizing the need for such programs [75]. In addition, better success and expansion of the repository programs can be realized with services or technologies that streamline donation, and inspection of donated medications. For instance, SIRUM, a non-profit organization in California, which provides streamlined donation packaging and shipping services, has now expanded into Colorado, Oregon, and Ohio [79,80].

Ruhoy et al., however, have determined that these "downstream" approaches may incur high costs and have inefficiently captured all medications accumulated as waste historically [12]. Instead, "upstream" approaches targeting the sources of pharmaceutical waste that can reduce the overall healthcare costs and burden of proper medication disposal should also be considered. Some of the recommended upstream approaches are unit packaging, providing trial scripts for new medications, low-quantity packaging of OTC medications, free samples, and drug repository programs that accept donations from patients [12]. Sweden has developed "Kloka Listan" or the Wise List that provides healthcare clinicians with a list of medications for common diseases recommended based on cost-effectiveness and environmental effects [53]. This type of comprehensive database would greatly help US health providers make more economical and environmentally appropriate decisions when prescribing.

#### *4.5. Limitations*

The findings suggested certain areas of improvement in healthcare and aspects for which patients and their household members should be better educated. As a household survey, however, the analysis did not reflect the medication use and storage by individuals. Some of the variables could have been more accurately and precisely collected. Both frequencies of use and storage locations did not specify the response collected as "other." The unit for quantities and strengths of medications, and the type of pets owned by the households were not specified as well. Sampling bias, recall bias and social desirability bias may have led to under-reporting of certain medications. Without collecting actual poisoning incidences and disposal methods, the results of the risk analyses could not be determinative. The Stockholm report that was utilized as the reference for the environmental risk analysis did not have conclusive evidence for various medications. Their Sweden-based data also may not be completely applicable in the US.

In-person and on-site assessment would be the most accurate method for evaluating medications stored at home and overcome the limitations that the current study had. The study by Sorenson et al. that found the association between the number of medications stored at home and the risk factors and health outcomes was done through in-person home visits in Australia [28]. Similar direct observations of the medication use, storage, and disposal by investigators in US homes may help tailor patient education and systemic interventions to minimize waste and maximize the efficiency of care and medication use.

#### **5. Conclusions**

Various areas of medications stored at home including, the use, storage, and poisoning and environmental risk, have been discussed in this paper. The study especially highlighted the negative implications of medications stored in US households. Notably, a significant portion of the medications stored in the participating households could put the vulnerable populations at risk of accidental exposure and harm the environment. Without studying more about these risks and their intricate associations with patients and household members, the society may keep suffering from the negative consequences. Thus, the findings attest to the dire need for more extensive research in this field to complements the limitations of the study. Those limitations include, but are not limited to, a small sample size and the explorative nature of the study that could not measure direct risks. Such research will guide efficient development and implementation of innovative interventions like medication reuse to prevent any potential harm.

**Author Contributions:** Conceptualization, S.L. and J.C.S.; methodology, S.L. and J.C.S.; software, S.L. and J.C.S.; validation, S.L. and J.C.S.; formal analysis, S.L.; investigation, S.L. and J.C.S.; resources, S.L. and J.C.S.; data curation, S.L. and J.C.S.; writing—original draft preparation, S.L.; writing—review and editing, S.L. and J.C.S.; visualization, S.L. and J.C.S.; supervision, J.C.S.; project administration, J.C.S.; funding acquisition, J.C.S. All authors have read and agreed to the published version of the manuscript.

**Funding:** The University of Minnesota provided funding for data collection and for software support (QualtricsXM; IBM SPSS Statistics 27; R v.4.1.0; and Microsoft Excel 2016).

**Institutional Review Board Statement:** University of Minnesota, Institutional Review Board Exempt from Full Review Number: HRP-503.

**Informed Consent Statement:** Your participation is voluntary and your response is confidential. Only aggregate responses will be reported. By completing the survey form, you are providing your consent to participate in the project.

**Data Availability Statement:** Data files are stored in encrypted format at University of Minnesota. Requests for access to the files may sent to the corresponding author at schom010@umn.edu.

**Acknowledgments:** Expert advice regarding research referenced in this paper from Ya-Feng Wen, Anthony W. Olson, Donald L. Uden, and Ronald S. Hadsall is greatly appreciated.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **Appendix A. Process of Assigning Medication Indications**

The categorization of indications intended to be as inclusive as possible without having much overlap among the indications. For instance, "cardiovascular therapy medications" included antihypertensive, anticholesteremic, antithrombotic, antianginal, and heartrate control medications. For medications with multiple active ingredients, their most likely common indication was assigned. For instance, the common indication of a combination of acetaminophen, dextromethorphan, and doxylamine was "cold," rather than a more specific indication for each ingredient. If the multiple active ingredients, however, did not have a common indication, all of their typical indications were assigned. For example, the indication of Yosprala containing aspirin and omeprazole was categorized as "cardiovascular therapy/gastrointestinal therapy." If a medication had multiple indications, the more commonly used indication was reported. For example, gabapentin was initially developed to treat seizures, but in current practice, it is predominantly used for neuropathic pain. Hence, for this study, its indication was categorized as "neuropathic pain." If one medication had multiple competing indications equally common in practice, then all of the indications were reported. For example, hydroxyzine was categorized as "mental health therapy" for its use for both anxiety and "allergies." For medications with various indications and without any distinct, predominantly common indications, their medication class was used for categorization. For instance, methotrexate which can be used for various

autoimmune diseases was categorized as "immunosuppressants." For responses classified as "duplicate," when a participant reported a medication in its brand name first and generic name afterward, for instance, Advil and ibuprofen, only the first response was assigned with an indication, and the rest was deemed "duplicate."

**Appendix B. Crude Responses (Prescription-only Non-Controlled Medications)**



#### **Appendix C. Crude Responses (Controlled Substances)**


#### **Appendix D. Crude Responses (OTC Medications)**



#### **Appendix E. "Duplicate" and "Invalid" Responses**


## **Appendix F. Complete Counts of Indications of Medications Stored in the Households (***N* **= 404)**



#### **References**


## *Commentary* **Stakeholder Views on the Idea of Medicines Reuse in the UK**

**Parastou Donyai 1, \* , Rachel McCrindle 2 , Terence K. L. Hui <sup>2</sup> and R. Simon Sherratt 2**


**Abstract:** People's views about medicines reuse are being examined in a handful of qualitative studies and this commentary adds to that work by drawing on our own discussions with groups of stakeholders in the UK in the past two years. The reuse of medicines within the community pharmacy setting is not permitted in the UK but our multidisciplinary team anticipates that this position will change in the coming years as medication shortages and worries about environmental waste and financial losses from the destruction of unused medicines are brought to the fore. Indeed, for many stakeholders, the issue of waste is a strong feature of conversations about medicines reuse. In addition to this, stakeholders identify the numerous barriers to medicines reuse in the UK. This includes the current uncertainty about the quality of unused medicines returned to pharmacies, which could otherwise be reused. However, stakeholders have also been very willing to propose solutions to a range of existing barriers. Our commentary draws on stakeholder meetings to elaborate the range of views about medicines reuse within a UK context. The challenge is to move forward from these views to advance the technologies that will facilitate medicines reuse practically as well as legally.

**Keywords:** medicines; reuse; recycle; medicines reuse; attitudes

## **1. Introduction**

A limited number of studies have examined people's views about the concept of 'medicines reuse' [1–4] and the purpose of this commentary is to add to this body of knowledge by reporting on our own discussions about the topic with groups of stakeholders in the UK in the past 24 months.

The concept of 'medicines reuse' itself is open to different interpretations and definitions. For example, some might understand it to relate to reusing a patient's own medicines when they are admitted to a hospital ward [5]; or the concept might be related to the recycling of medicinal components or packaging in future manufacturing processes [6]. The phrase medicines reuse has also been used to refer to the repurposing of old drugs for new conditions. A number of related terminologies also exist, including re-dispense, recycle, redistribute and reverse flow. These ideas and related concepts, although important, are not the focus of the current paper. Here, we use the term 'medicines reuse' to mean the idea that within a community pharmacy context, "medication returned by one patient can be dispensed by a pharmacist to another patient (instead of disposal as waste–which is what currently takes place)". Our paper is focused within a UK context, where pharmacists working within community pharmacies are not permitted to reuse medicines. What prevents medicines reuse in this setting is a combination of the law, professional guidance and past precedence.

In the UK, apparently how a medicine is sourced is not generally relevant as long as a medicine is supplied in accordance with the relevant prescription, for the specific purposes of part 12 of the Human Medicines Regulation 2012 [7]. However, reusing medicines

**Citation:** Donyai, P.; McCrindle, R.; Hui, T.K.L.; Sherratt, R.S. Stakeholder Views on the Idea of Medicines Reuse in the UK. *Pharmacy* **2021**, *9*, 85. https://doi.org/10.3390/ pharmacy9020085

Academic Editor: Jon Schommer

Received: 7 March 2021 Accepted: 13 April 2021 Published: 16 April 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

reportedly invalidates the terms and conditions under which medicines are supplied from wholesalers [8]. Additionally, because legislation governing the supply of medicines requires persons trading medicines (other than directly supplying to patients) to hold a wholesale dealer's license [unless supplies are small, take place occasionally, are not-forprofit and not for onward wholesale distribution], this legislation also limits the receipt and redistribution of returned medicines between different units/legal entities along a supply chain (e.g., from one pharmacy to another) [9]. Furthermore, under normal circumstances, medicines reuse is not recommended by the Department of Health because the quality of any medicine that has left the pharmacy cannot be guaranteed [10,11]. In fact, in the UK, none of the regulatory and professional bodies currently support the reuse of medicines within the community pharmacy setting. This includes the Medicines and Healthcare Products Regulatory Agency (MHRA), the Association of British Pharmaceutical Industries (ABPI), the General Pharmaceutical Council (GPhC), the National Health Service (NHS), the British Medical Association (BMA), and the Royal Pharmaceutical Society (RPS). Our research group, however, is investigating the sustainability of this position.

Based on existing knowledge about pharmacy and the technology that might be integrated within pharmaceutical packaging, our multidisciplinary team Reuse of Medicines through Informatics, Networks and Sensors (ReMINDS) (www.reading.ac.uk/ReMINDS, accessed on 14 April 2020) is composed of academics from the pharmacy, computer science and biomedical engineering fields at the University of Reading. 'ReMINDS' communicates our opinion on medicines reuse candidly (we are pro researching medicines-reuse) so our paper is arranged as a commentary rather than a research paper, the aim being to present new viewpoints on an existing problem, while also drawing on original data. Here, we draw on key themes conveyed to our group by a range of stakeholders in meetings organized to discuss medicines reuse, while acknowledging that our paper is imbued with personal opinion, in line with Berterö's definition of a commentary [12].

We draw on our discussions with a range of stakeholders that includes young people, future pharmacists, pharmacists working within the primary-care, community, hospital, and homecare settings, pharmaceutical industry representatives, specialists in medicines supply, patients, and researchers.

#### **2. The Wastage of Medicines**

Medicines reuse as a concept stems from the problem of medication waste. After all, if there was zero medication wastage, there would be no medicines *to* reuse. Thus, a range of ideas about medicines reuse are expressed by people, directly in relation to the creation and prevention of medication waste.

A range of practices and settings are thought to contribute to medication waste. For example, using multi-compartment compliance aids (MCCAs) as a practice is thought to be wasteful; in MCCAs, individual doses, having been removed from their packaging, are placed with other medicines within distinct compartments a month or more in advance of actual consumption, rendering the medicines 'expended' as soon as the MCCA is prepared. Then if a patient's medication regimen is changed (e.g., a medication is discontinued), the entire content of their MCCA becomes unusable for that patient—this is because it is too risky to remove individual discontinued tablets from the compartments (risk of error) so the entire contents have to be discarded once the regimen changes. MCCAs are utilized widely within care homes, where there is also a notion by some stakeholders that care-home staff contribute to the wastage of medicines by excessive reordering and the stockpiling of medicines.

Outside of formal care settings, another factor associated with medication waste is medication non-adherence, where patients fail to fully follow the dosage instructions of their medication, for example by not taking their medicines at all or failing to complete the full course. The reasons for non-adherence are complex, multi-factorial and well researched but some noteworthy insights from our patient stakeholders include the need to create conditions that allow patients to disclose their real medication-taking patterns, and to address their fear, disinterest or lack of understanding about medicines, some of which are potentially engendered, it seems, through the physical appearance (design/text) of medicinal packaging.

An additional behaviour recognized and discussed by our stakeholders is the unnecessary/over ordering of medication, for example patients ordering large pack sizes, and stockpiling medication, or over/inappropriate prescribing by doctors. This issue is especially important in the UK since patients are sometimes seen not to be 'accountable' for behaviours such as over-ordering, because many do not directly pay for their medication and bear none of the financial costs. There is arguably then no real barrier to intentional or unintentional medication stockpiling, with some of the people we have spoken to suggesting that notifying patients about the monetary cost (albeit to the NHS) of their medicines (e.g., printing the price on the medicinal packet) might incentivize more responsible re-ordering behaviours—or that in any case alerting patients of their responsibility to reduce the NHS medicines spend is a worthwhile activity.

Doctors, pharmacists and other health professionals are also considered key actors who can reduce medicines waste by 'taking responsibility' for more sustainable practices. For example, by checking, discussing and challenging quantities and medicines being re-ordered, completing medication reviews to ensure rational prescribing, prescribing lower quantities for more expensive medicines or medicines that are new to patients, and ensuring better stock control (including liaising with wholesalers and delivery companies) to avoid accumulating short-dated items (including on hospital wards) or ending up with medicines that are kept at the wrong storage temperature. Related to this is the notion of deprescribing (stopping superfluous medicines), which some patients and doctors avoid out of fear (of therapeutic repercussions). Finally, as patients' own drugs (PODs) can still be used if they are admitted to hospital, another challenge is to ensure patients take their current medicines to hospital, to avoid duplicate dispensing, especially important where people have multiple admissions to hospital within a short period of time. Of course, this is not to deny that some PODs are judged to be of insufficient quality by hospital staff and re-dispensed in any case.

#### **3. Barriers to Medicines Reuse**

Similar to that reported elsewhere, our stakeholders had some concerns about medicines reuse. This included questions about the quality and safety of returned medicines and how these might be checked for suitability; and whether patients and consumers really store their medicines correctly at home, especially medicines requiring cold storage—and how people might be educated to do so. Our stakeholders recognized the potential for errors or contamination to occur within the supply chain. Further, they wondered about the cleanliness and potential for contamination of returned medication packs.

One of the concerns about medicines reuse relates to the practicality of operating such a scheme in UK community pharmacies. Community pharmacists have limited time for additional services, meaning that the addition of a medicines reuse scheme would doubtless require effective resourcing and incentivization. It also necessitates additional guidance and standard operating procedures for the receipt, separate storage, quality-assurance, and supply of reusable medicines within relatively small pharmacy spaces. National pharmacy bodies, for example, would be expected to publish consensus guidelines on medicines reuse. Or the NHS might consider taking back returned medication for storage and re-distribution. An additional challenge within community pharmacies relates to the reimbursement of prescription costs and the audit trail needed to prevent duplicate payments to pharmacies, while ensuring pharmacies are paid for the cost of administering medicines reuse.

There is also an expectation for medicines reuse to be financially logical, with implementation costs having to balance against the cost of the original medication. For example, any additional technology that might track the medicine's storage conditions, batch number, manufacturing date/product age, expiry date, etc., to manage resupply, should reasonably

be cost-effective. Stakeholders also highlight the potential paradox of having to add to a medicine's carbon footprint in order to reduce its waste—the environmental harm of medicines reuse (e.g., via any additions to the packaging) must thus balance against that created by the medicine's potential wastage if unused.

Two points came up specifically when we spoke to younger people about medicines reuse. Some conceptualized reuse as the process of taking back medicines and re-extracting the constituent elements. For packaged medicines, they thought that these are already routinely sent to other (poorer) countries for their use, but this practice is discouraged by the World Health Organisation which sees it as operating double standards.

Stakeholders pose other relevant questions within the UK context, including whether multiple re-use (re-dispensing) of a medicine might be permitted, and how recall of medicines might affect re-dispensed medicines. Another important issue is how current legislation to hold a wholesale dealer's licence impacts on medicines reuse across different sections of the NHS.

A related matter concerns the falsified medicines directive (FMD), which describes a set of measures introduced in the European Union for the regulation of medicines trade, to prevent the appearance of fake medicines in the legal supply chain. February 2019 saw the implementation of two specific safety features on medicines determined by FMD; a unique identifier (a 2D data matrix code with product code, serial number, batch number, expiry date) on medicinal packaging scannable at fixed points along the supply chain, and tamper evident features (anti-tampering devices) on the pack. Thus, medicines can be verified in their movement through the supply chain, and 'decommissioned' at the final point, on supply to the patient. The stakeholders we engaged with duly ask how medicines then might be placed back within the supply chain in light of FMD, and how the safety features determined by FMD might be harvested to verify medicines for reuse. However, FMD will no longer apply in the UK following its exit from the European Union in 2021, and while this negates the need to 're-commission' a medicine, the absence of safety features that might prevent falsified medicines from entering the supply chain is a less constructive step for medicines reuse.

#### **4. Towards Solutions**

Medicines reuse is not currently permitted in the UK but there have been ample questions and ideas from our stakeholders on how to promote engagement with such a scheme in the future. Some questions are, for example, how people might be incentivized to return their unused medicines to pharmacies in the first place, especially within the shelf life of the product. And how they might be educated to store their medication correctly at home to start with. How the stigma around returning medicines to pharmacies might be reduced—after all, these are medicines that would have been ordered/accepted but then left unused. Further, is there a need to take consent before supplying 'reused' medicines? How might we tackle negative perceptions about receiving what some might consider to be 'second-hand medicines', such that medicines reuse becomes socially acceptable, or indeed an obligation in light of eco-friendly movements? Perhaps in the future there might even be a system where people actively 'opt out' of receiving medicines within a reuse scheme.

Suggestions for changing popular opinion and social norms include teaching about the importance of medicines reuse, communicating success stories, and reshaping misconceptions about 're-used' medicines. Stakeholders believe incentivizing uptake, or at least quantifying the overall benefits of medicines reuse could encourage engagement. For example, reusing medicines to prevent medicines shortages is a logical aim. Patients also want clearer information about the current fate of medicines returned to pharmacies. Other suggestions are to learn from existing groups such as 'free cycle', and to train pharmacists and other staff to promote engagement with medicines reuse, and indeed sustainable pharmacy more broadly, and engaging with popular media, celebrity advocates and social media influencers. The use of social media and technology (e.g., smartphones) is seen as plausible, indeed inevitable but patients also express that any developments in this area

should be inclusive of older people, who use medicines the most, and poorer patients who might lack access to the newest smartphones.

The support of a range of official bodies too is seen as important for sanctioning medicines reuse in the first place, none of which currently approve medicines reuse within the community pharmacy setting. For example, engaging with medicines reuse might become a part of the community pharmacy contract and embedded within the pharmacy professional standards. Or administering medicines reuse might formally become one of the responsibilities of support staff within a pharmacy. Stakeholders suggest drawing on the experience of similar schemes in Greece [13] and the US [14] to overcome existing barriers to medicines reuse, and aiming to make medicines reuse as acceptable as reusing coffee cups and plastic bags.

Pharmaceutical companies are seen to play a key role and perhaps there could even be tax breaks for companies proactively changing their practices to facilitate reuse; or other incentives in lieu of their social responsibility. For example, pharmaceutical companies are recognized for holding primary raw data relating to the stability of medicines under different storage conditions—gaining access to these data might enable researchers to model and predict the integrity of medication stored in different home environments, to help define medication reuse criteria. Pharmaceutical companies might also explore whether *medication packaging* could be modified to colour-code sensitivity to environmental conditions, increase tolerance to these conditions, accommodate time/temperature indicators or other technology within the surface, or become more sustainable in itself. They might extend the usable shelf life of medicines. They might invest in the development of a secure supply chain for the return of medicines, sustainable technology that monitors medicine integrity during storage and use, or indeed tracks its whereabouts, and provide assurances about the safety, quality and cleanliness of returned medicines. Such technology would need to be secure and ensure the privacy, and even liberty of users. It would also need to be mindful of the primary users of medicines—for example, to prevent creating alarm if a visual quality indicator shows a potentially 'invalidated' medicine during first use.

Hospital pharmacies are recognized for their policies on medicines reuse (for using PODs), and pharmacies in general have risk management tools, which stakeholders expressed would be useful to learn from.

In terms of legislation, our stakeholders recognized the importance of engaging with the various professional and regulatory bodies to enable medicines reuse, recognizing the time and effort that would be required. Activities might include lobbying the MHRA for an exemption that would allow medicines to be reused within the community pharmacy setting; or illustrating potential cost savings to the Department of Health, at least for high-cost items or where drugs are vulnerable to shortages.

#### **5. Discussion**

Our stakeholders' ideas about the wastage of medicines can be summarized as relating to practices around MCCAs, especially in care homes, medication non-adherence, overordering, over-prescribing, improper stock control and inadequate use of PODs. Their concerns about medicines reuse relate to the quality and safety of returned medicines, pharmacy resources and incentivization to deal with the process, the cost-benefits of such a scheme, and legislative barriers. Finally, their proposed solutions centre on educating and incentivizing the public, removing stigma around returning and reusing medicines, defining consent processes, using technology and social media, engaging with official bodies and the pharmaceutical industry, learning from existing practices in hospitals and lobbying regulators to change the law.

The issues identified as contributing to waste have long been recognized by others and in fact mirror many of the findings of a seminal report on the scale, causes and costs of waste medicines published in 2011 [15]. Indeed, the problem of medication waste is one of the main reasons for debating medicines reuse. This is alongside the high cost of medication, for example expensive cancer drugs in developed countries [16] and the cost of

a range of other drugs for chronic and communicable diseases in developing countries such as India [17]. A small pilot in Singapore has also identified the huge potential for medicines reuse to reduce medication wastage and costs [18]. Researchers examining the benefit of long-term donation programmes in Europe, Africa and Latin America, against WHO's formal advice to withhold such donations, also report a decrease in expenditure by both patients and health facilities [19]. The issue of lack of accountability for the over-ordering of medicines identified by our stakeholders associated with free prescriptions has also been debated before, with one suggestion being to charge a nominal £1 fee for prescription items to create a symbolic contract for patients to take their medicines more responsibly [20].

Some of the concerns relating to medicines reuse expressed by our stakeholders, as well as their proposed solutions, also feature in the limited number of studies that have systematically examined medication reuse. For example, Bekker and colleagues who examined views about medicines reuse in The Netherlands in 2014/15 identified two central requirements for the re-dispensing of returned medicines; namely, patient willingness to use and trust re-dispensed medicines and guaranteed product quality of re-dispensed medicines [2]. System requirements in that study were identified as relating to legal feasibility, financial aspects that should be taken into account and the roles stakeholders can fulfil [2]. Interestingly, in 2014 Liou and colleagues devised a quality control programme to ensure the safe recycling of metered dose inhalers within a hospital setting, focusing on microbial decontamination of the partially used devices [21]. When McRae and colleagues interviewed pharmacists in the UK about medicines reuse in 2014, they identified a range of criteria to be met for pharmacists to potentially accept the redistribution of tablet and capsule medication: "protection for pharmacists; guidance from the professional regulator; tamper evident seals; 'as new' packaging; technologies to indicate inappropriate storage and public engagement" [22]. Our own findings from interviews with members of the public in the UK exploring medicines reuse beliefs in 2016 was structured around the theory of planned behaviour [3]. We reported views on the potential economic and environmental benefits of medicines reuse alongside people's worries about medication stability and safety. Our participants then also wondered if pharmacists had the time and storage space to dedicate to medicines reuse. The physical characteristics of reused medicines, and quality assurance and logistics of reuse processes were also seen to enable/obstruct engagement in medicines reuse [3]. Thus, our stakeholders' views outlined here appear to chime with the concerns expressed by others in the past, and appear to be valid and reasonable to address.

While the number of studies in this field are limited, it is also clear that once people are consulted, there is an appetite for exploring how to make medicines reuse safe, and a limited number of ideas on how to do so in practice. One of the ideas that appears to be unique to our own exploration of views here is to engage pharmaceutical companies in sharing their raw stability data to be programmed into a system for monitoring the impact of storage conditions on the continued stability of medication stored in a patient's home. We also found it interesting that when talking to our younger stakeholders, they imagined medicines reuse was already taking place, albeit at least via donations to developing countries. What is important about our work is that is brings together the views of a range of participants and reflects the latest thinking in this area. However, it is also interesting to note that as far back as 2007, Mackridge and Marriott spotted the potential that by using "modern packaging techniques, including tamper-evident seals and 'smart' labels that react to temperature and humidity, it would be possible to identify inappropriately stored medicines" [23].

#### **6. What Next**

Alongside stakeholder consultations described here and elsewhere [3], we have been progressing some of the practical ideas relating to medicines reuse within our multidisciplinary ReMINDS team. A review of the literature has allowed us to suggest a novel ReMINDS ecosystem as a solution for reusing returned prescribed medicines [24]. This system relies on active sensing technologies integrated with the Internet of Things plat-

form to validate the quality and safety of medicines while interconnecting the relevant stakeholders. Additionally, we have developed the prototype for a novel digital time, temperature and humidity indicator using smart sensors with cloud connectivity as the key technology for verifying and enabling the reuse of returned medicines [25]. The past year has also seen a global pandemic impacting on the supply of medicines which in the UK has resulted in the temporary approval of medicines reuse within the hospice and care home sectors [26]. Our challenge now is to learn from the reuse of medicines within these settings and continue to explore the technological ways in which medicines reuse can be further progressed.

**Author Contributions:** P.D. prepared, reviewed and revised the manuscript. R.M., T.K.L.H. and R.S.S. critically reviewed and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded through the University of Reading Research Endowment Trust Fund (RETF), and the Building Outstanding Impact Support Programme (BOISP).

**Acknowledgments:** We would like to thank our stakeholders who have engaged with us on the topic of medicines reuse over the past 24 months. We specifically thank Tracey Duncombe for facilitating one of the stakeholder meetings we held in 2019.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

