1 10.1515/sjph-2016-0022_Zdrav Var 2016; 55(3): 195-178 Paut Kusturica M, Tomas A, Tomic Z, Bukumiric D, Corac A, Horvat O, Sabo A. Analysis of expired medications in Serbian households. Zdrav Var 2016; 55(3): 195-201 ANALYSIS OF EXPIRED MEDICATIONS IN SERBIAN HOUSEHOLDS ANALIZA KOPIČENJA ZDRAVIL S PRETEČENIM ROKOM TRAJANJA V SRBSKIH GOSPODINJSTVIH Milica PAUT KUSTURICA1*, Ana TOMAS1, Zdenko TOMIC1, Dragica BUKUMIRIC1, Aleksandar CORAC1, Olga HORVAT1, Ana SABO1 'University of Novi Sad, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Hajduk Veljkova 3, 21000 Novi Sad, Serbia Original scientific article Introduction. An ongoing issue of expired medications accumulating in some households is a universal problem around the world. The aim of the study was to investigate the extent and structure of expired medications in Serbian households, and to determine which therapeutic groups generated the most waste. Methods. This was an observational, cross-sectional study conducted in households in the city of Nov' Sad, Serbia. The study had been performed over 8 month period (December 2011 - July 2012) and it consisted of personal insights into the medication inventory in households. Results. Of 1008 families, 383 agreed to participate and complete the questionnaire (38.3% response rate). In almost a half of households (44.4%), expired medications were maintained. The amount of expired medications was 402 items, corresponding to 9.2% of total medications presented in surveyed households. The majority of expired medications (64.7%) was in solid dosage (tablets, capsules, granules, lozenges), following semisolid (ointments, creams, gel, suppositories) and liquid dosage forms (drops, syrups). Expired medications in the households belonged mostly to 3 categories: antimicrobials for systemic use (16.7%), dermatological preparation (15.9%) and medications for alimentary tract and metabolism (14.2%). Conclusions. This study revealed that there were relatively large quantities of expired medications in Serbian households, with a high prevalence of antibiotics for systemic use, anti-inflammatory and antirheumatic products, and medications for alimentary tract and metabolism. Received: Sep 15, 2015 Accepted: Mar 21, 2016 ABSTRACT Keywords: drug wastage, households, expired medications, Serbia IZVLEČEK Ključne besede: odpadna zdravila, gospodinjstva, zdravila s pretečenim rokom trajanja, Srbija Uvod. Težava s kopičenjem zdravil s pretečenim rokom trajanja v gospodinjstvih je velik problem po vsem svetu. Cilj te študije je bil raziskati obseg in sestavo zdravil s pretečenim rokom trajanja v srbskih gospodinjstvih in določiti, katere terapevtske vrste zdravil predstavljajo največji odpad. Metode. Opazovalna, presečna raziskava je bila izvedena v srbskih gospodinjstvih v Novem Sadu. Trajala je osem mesecev (od decembra 2011 do julija 2012). Sestavljena je bila iz osebnega vpogleda v zalogo zdravil v gospodinjstvih. Rezultati. Od 1008 družin se jih je 383 odločilo za sodelovanje in izpolnilo vprašalnik (38,3-odstotna odzivnost). V skoraj polovici gospodinjstev (44%) so imeli zdravila s pretečenim rokom trajanja. Skupno sta bili najdeni 402 zdravili s pretečenim rokom trajanja, kar predstavlja 9,2% vseh zdravil v anketiranih gospodinjstvih. Večina zdravil s pretečenim rokom trajanja (64,7%) je bila v trdi obliki (tablete, kapsule, granule, lozenge), sledila so zdravila v poltrdni obliki (masti, kreme, geli, suspenzije) in tekočine (kapljice, sirupi). Večina zdravil s pretečenim rokom trajanja v gospodinjstvih pripada eni od naslednjih treh skupin: antimikrobna zdravila za sistemsko rabo (16,7%), dermatološki preparati (15,9%) in zdravila za bolezni prebavil in presnove (14,2%). Zaključki. Raziskava je pokazala, da je v srbskih gospodinjstvih shranjenih relativno veliko zdravil s pretečenim rokom trajanja. Najpogosteje se pojavljajo antibiotiki za sistemsko uporabo, protivnetni in antirevmatski pripravki ter zdravila za bolezni prebavil in presnove. Corresponding author: Tel: ++ 381 21 522 172; E-mail: milicapaut@yahoo.com NIJZ Brought to you by | National & University Library Authenticated National Institute i' National Institute of Public Health, Slovenia. ^^ '"""V™ 195 of Public Health This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (w£&65 years or children aged <12 years in their households), this information was also recorded. The second part of the Brought to you by | National & University Library Authenticated 196 Download Date | 11/14/16 8:02 AM 196 10.1515/sjph-2016-0026 Zdrav Var 2016; 55(3): 202-211 questionnaire focused on questions (3) related to expired medications and their disposal. Statistical analysis was performed with SPSS software (SPSS 15.0 for Windows, SPSS Inc., Chicago, IL USA). Descriptive statistics on the distribution of the number of packages in the surveyed households was performed. For parametric data of independent samples t-test was used to test differences between groups. For numeric data with non-normal distribution and ordinal data MannWhitney U test was used. Chi-square test was used to test differences between nominal data (frequencies). All p values less than 0.05 were considered significant. 3 RESULTS In almost a half of households (170, 44.4%), expired medications were maintained. The total amount of expired medications was 402 items, corresponding to 9.2% of all medications present in surveyed households. Of the total expired medications, 70.4% were prescription-only and 29.6% were over-the-counter (OTC) medications. The majority of expired medications (260, 64.7%) were in solid dosage forms (tablets, capsules, granules, lozenges), following semisolid (ointments, creams, gels, suppositories) and liquid dosage forms (drops, syrups) (Table 1). Table 1. Dosage forms of expired medications. Table 2. Dosage forms of expired medications. Dosage forms Items N % Tablets, capsules, dragées, lozenges, powders 260 64.7 Ointments, creams, gel, suppositories 88 21.9 Drops, syrups 48 11.9 Inhalers, sprays 6 1.5 Total 402 100.0 Expired medications classified according to ATC classification are presented in Tables 2 and 3. Predominant therapeutic groups among expired medications were anti-infectives for systemic groups (16.7%), dermatologicals (15.9%) and medications for alimentary tract and metabolism (14.2%). ATC N % J-anti-infectives for systemic use 67 16.7 D-dermatologicals 64 15.9 A-alimentary tract and metabolism 57 14.2 M-musculo-sceletal system 48 11.9 R-respiratory system 46 11.4 N-nervous system 44 10.9 C-cardiovascular system 27 6.7 S-sensory organs 18 4.5 B-blood and blood forming organs 15 3.7 G-genito-urinary system and sex hormones 13 3.2 H-systemic hormonal preparations, excluding sex hormones and insulins 2 0.5 P-anti-parasitic products, insecticides and repellents 1 0.2 L-antineoplastic and immunomodulating agents 0 0 Grand Total 402 100 Table 3 . ATC therapeutic categories (level II) of expired medications. ATC Therapeutic groups N % J01 Antibacterials for systemic use 66 16.4 M01 Anti-inflammatory and antirheumatic products 35 8.7 N02 Analgesics 31 7.7 D07 Corticosteroids, dermatological preparations 25 6.2 D06 Antibiotics and chemotherapeutics, dermatological 24 6.0 R01 Nasal preparations 22 5.5 A07 Antidiarrheals, intestinal anti-inflammatory/anti-infective agents 17 4.2 R05 Cough and cold preparations 13 3.2 S01 Ophthalmologicals 12 3.0 A03 Drugs for functional gastrointestinal disorders 11 2.7 B03 Antianemic preparations 11 2.7 A02 Drugs for acid related disorders 11 2.7 Other 278 69.0 Total 402 100.0 Brought to you by | National & University Library Authenticated 197 Download Date | 11/14/16 8:02 AM 197 10.1515/sjph-2016-0030 Zdrav Var 2016; 55(3): 218-224 The opinion of the majority of the respondents was that medications should not be used after the expiration date (75.2%). However, a fifth of the respondents (20.4%) agreed that medications can be used 6 months after the expiration date. Despite the fact that the majority of respondents (66.3%) think throwing medications into the garbage has detrimental effects on the environment, this was the predominant disposal method among the surveyed households (82.8%). Only 4.4% of the respondents reported returning expired medications to a pharmacy (Table 4). Table 4. Participants' responses to the question related to expired medications and their disposal. The availability of expired medications to children N % yes 91 69.6 no 41 30.4 total 132 100.0 In your opinion, can medicationsbe used after the expiration date? N % yes 10 2.6 yes, 6 month after the expiration date 78 20.4 no 288 75.2 don't know 7 1.8 Do you think that disposal of expired medication into the garbage has detrimental effects on the environment? N % yes 254 66.3 no 52 13.6 don't know 77 20.1 How do you currently dispose of expired medications? N % into the garbage 317 82.8 flush down the toilet or sink 11 2.9 return to pharmacy 17 4.4 store 3 0.8 burn 7 1.8 always use till the end 28 7.3 total 383 100.0 As presented in Table 5, the number of expired medications in households was significantly associated with the family size, level of respondents' education, presence of children younger than 12 years (p<0.05). Table 5. Demographic and socioeconomic characteristics associated with expired medications in households. Variable Households with no expired medications Households with p expired medications Family size 2.7±1.2 3.0±1.1 0.002 Gender 0.963 male 43 (20.1%) 34 (20.0%) female 170 (79.9%) 136 (80%) Elderly >65 0.094 years no 183 (85.9%) 156 (91.8%) yes 30 (14.1%) 14 (8.2%) Education 0.007 elementary 18 (8.4%) 9 (5.3%) school secondary 103 (48.3%) 66 (38.8%) school junior college 15 (7.1%) 10 (5.9%) degree 77 (36.3%) 85 (50.0%) Occupation 0.088 employed 106 (49.7%) 107 (62.9%) unemployed 39 (18.3%) 23 (13.5%) student 12 (5.6%) 6 (53.5%) retiree 56 (26.3%) 34 (20.0%) Children <12 0.019 years yes 64 (30.0%) 71 (41.8%) no 149 (70.0%) 99 (58.2%) 4 DISCUSSION 4.1The Extent and Type of Expired Medications in Serbian Households To the best of our knowledge, our study analysed for the first time the contents of a pharmaceutical waste generated in households in Serbia. Although this study collected information on the percentage and types of medications that expired without investigating the underlying reasons for not using them, it provides evidence to an under-researched area. The findings are mostly consistent with other studies in terms of the percentage of expired medications, but varied in the most common therapeutic groups. The extent of expired medications in Serbian households of 9.2% is comparable to those reported in Croatia, where Brought to you by | National & University Library Authenticated Download Date | 11/14/16 8:02 AM 223 10.1515/sjph-2016-0030 Zdrav Var 2016; 55(3): 218-224 expired medication comprised 10.8 medication supplies (17). of total household More than 70% of expired medications in Serbian households were prescription-only medications. The existence and extent of expired prescription medications could be adopted as a direct measure of non-compliance and poor adherence by the patient population, as demonstrated in many studies. For example, in the United Kingdom, only one third of people surveyed did not complete a course of the prescribed medication. In addition, more than 20% of the prescribed medications in British homes were not being taken, while 14% of prescribed medications were partly used. In an Iranian and the British study, approximately 10% of patients who filled their prescriptions have never taken the prescribed medications (12). Notwithstanding the reasons for leftovers of prescription medications, these medications can definitely lead to unintentional pharmaceutical poisonings of children, facilitate abusive use, and promote emerging social problems, such as teenage "pharming", a recreational use and abuse of prescription medications among teenagers (18). The structure of expired medication according to the type of formulation was similar to other studies with by far the highest percentage of solid dosage forms, followed by semisolids (e.g. crème, ointments) (15). In our study, the expired medications in the households belonged mostly to 3 categories: anti-microbials for systemic use, dermatological preparations, and medications for alimentary tract and metabolism. On the contrary, both Mexican and U.S. studies reported the painkillers and cardiovascular medications as the most common expired medications, while antibiotics occupied the third place (15, 16). In our opinion, as these studies were carried out in different countries, these differences are potentially attributable to the difference in demographic characteristics, health seeking practices or different supply ways of medications in surveyed households. However, the main reason for large quantities of expired antibacterials stored in Serbian households was easy access. This study was conducted just after Serbian authorities enforced stricter law rules regarding antibiotics' acquisition in November 2011. Until then, antibiotics were routinely available without a medical prescription in private pharmacies. The second possible reason for the levels of storage of antibacterial medications is patients' non-compliance with recommended treatments. The presence of expired antimicrobial agents implicates that the patients did not complete the full dispensed course, and left-over antibiotics might later be used for self-medication without proper indication, in insufficient quantities, or even when contraindicated (7, 19). In contrast to a Mexican study, where dermatological preparations comprised less than 2% of all medications expired, they ranked second in households in Novi Sad, with mostly topical antibiotics and corticosteroids. Expired medications from alimentary tract category were also commonly encountered in Serbian households. Many of the gastrointestinal tract (GIT) medications are OTC medications (e.g. antacids, laxatives), which could partially explain the high percentage of expired GIT medications. Abushanab et al. also identified medications for alimentary tract and dermatologicals as the medications that commonly go unused and expire (19). Surprisingly, the expired cardiovascular medications comprised a noticeably lower percentage of expired medication in households than in other studies (15, 16). This discrepancy could be partially attributed to the demographic characteristics of surveyed Serbian households (e. g. low presence of persons older than 65). In addition, Serbian National Health Insurance Fund allows for chronic disease medications, including cardiovascular medications, to be prescribed in maximum two months' course, definitely decreasing the possibility of the medication passing the expiry date. A high percentage of medications belonging to musculoskeletal (mostly antiinflammatory and antirheumatic products) and nervous system (mostly analgesics) was also demonstrated in other studies (11, 16, 18, 22). 4.2 Expired Medications and their Disposal The attitude of around a fifth of the Serbian respondents is that medication can be used up to 6 months after the expiration date, while the majority thought that expired medications should not be used. This is in accordance with the general opinion that expiration date is the end of the useful life of the medication. However, this may not be necessarily true, since the labelled expiration date is the final day that the manufacturer guarantees the full potency and safety of a medication, while the actual shelf life of some products is, in fact, longer (15). Despite the fact that Serbian public was generally concerned on how improper medication disposal detrimentally effects the environment, the behaviour regarding disposal of unused medications did not equate the awareness. A previous study carried out in South Backa District, Serbia, showed that environmental awareness may not necessarily affect how people dispose of their medications, because other factors, such as the availability of formalized disposal protocols, may also play an important part (7, 20). However, according to Food and Drug Administration (FDA) recommendations, where no organized collection system exists, a disposal of medications in domestic garbages destined for landfills is accepted as more environmentally friendly than flushing them down the drain. Actually, in this situation, Brought to you by | National & University Library Authenticated Download Date | 11/14/16 8:02 AM 223 1 10.1515/sjph-2016-0022 Zdrav Var 2016; 55(3): 79-178 medications may be disposed of in the household trash by removing them from their original containers, mixing them with unpalatable substances, such as kitty litter or used coffee grounds, placing the mixture in a sealed plastic container, and putting that sealed container into the household trash (21, 22). Disposal of expired medications into the garbage, the leading method of disposal in Serbia, has also been identified as the predominant way of disposal in Kuwait, United Kingdom and Lithuania (4). Disposal of medications into the sewage system is still a common practice in New Zealand, USA and Bangladesh, and is mostly reserved for liquid dosage forms (6, 23, 24). In contrast, in Sweden, a country with a long tradition of the reverse distribution network for the collection of unused and unwanted medications, a high percentage of population returns unused medications to pharmacies (43%). Sweden is an excellent example of how the essential part of communicating a message to the public is to postulate a clearly defined mechanism for disposal and an unambiguous obligation on specified agent/agencies to take medications for disposal (25). Also, confusion over the adequate methods of medication disposal still exists in many countries, mostly because of conflicting or incomplete guidelines for disposal of unused medications (4). 4.3 Limitations Despite the fact that an in-home inventory of medications obtained by direct observation has been shown to be a more reliable measurement tool than self-report recall methods, some weaknesses of our study need to be mentioned. First of all, it may be difficult to extrapolate our study results to the other parts of our country, because Novi Sad, a wealthy university city, might not be representative of Serbia in general. Secondly, answers to the questions regarding disposal habits and attitudes are self-reported in nature, and some respondents may not have been telling the truth. Notwithstanding these limitations, the study adds information to the area of scant knowledge. 4.4 Study Implications Serbia must seriously consider the issue of medication wastage. A part of this wastage can be prevented and, considering the limited health resources of the country, it is prudent to start taking action. Firstly, like in many countries, Serbian government should limit prescription medication wastage by dispensing medication according to the exact number needed for treatment, rather than by the original pack, and also by increasing compliance through educational campaigns targeting different age groups and using various communication routes. Also, in order to limit environmental effects of improper expired medication disposal, an established formalized state-run disposal system that is cost-effective and easily accessible is necessary in Serbia. 5 CONCLUSIONS This study revealed that expired medications were commonly encountered in Serbian households, with a high prevalence of antibiotics for systemic use, anti-inflammatory and antirheumatic products, and medications for alimentary tract and metabolism. Throwing medications into the garbage was the predominant disposal method among the surveyed households, despite the fact that more than a half of the population is aware of the harmful effects of improper medication disposal on the environment. CONFLICTS OF INTEREST The authors declare no conflicts of interest. FUNDING This work was supported by the Ministry of Science and Technological Development, the Republic of Serbia, Project No. 41012. ETHICAL APPROVAL Received from the Ethical Committee of the Faculty of Medicine in Novi Sad. REFERENCES 1. Bound JP, Voulvoulis N. Household disposal of pharmaceuticals as a pathway for aquatic contamination in the United Kingdom. Environ Health Perspect 2005; 113: 1705-11. 2. Vogler S, Leopold C, Zuidberg C, Habl C. Medicines discarded in household garbage: analysis of a pharmaceutical waste sample in Vienna. J Pharm Policy Pract 2014; 7: 6. 3. Coma A, Modamio P, Lastra C, Bouvy M, Marino. 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