The Perception and Disposal Practices of Unused And Expired Medicines By Households In an Urban Municipality, Southwest Nigeria: A Comparative Cross-Sectional Study

Olufemi O. Aluko (  ooaluko@gmail.com ) Obafemi Awolowo University https://orcid.org/0000-0002-5726-5806 G. T Imbianozor Obafemi Awolowo University Faculty of Clinical Sciences C. O. Jideama Obafemi Awolowo University Faculty of Clinical Sciences O. V. Ogundele Obafemi Awolowo University Faculty of Clinical Sciences T. E Fapetu Obafemi Awolowo University Faculty of Clinical Sciences Olusegun T. Afolabi Obafemi Awolowo University Faculty of Clinical Sciences

In the study area, water treatment systems and regulations do not monitor drugs residues as an indication of potability [10,13] and there are pieces of evidence that improper disposal of drugs could contaminate water resources while active pharmaceutical ingredients (APIs) persists in the environmental media [8]. Also, ingestion of expired drugs that were inappropriately discarded may lead to toxicity and drug resistance. [14].
In the study area, it is a common practice to keep unused and, or expired medications in homes after discontinued use or excesses purchased for self-medication. Usually, expired drugs are not supposed to be disposed of with household refuse and as such when disposed of, may herald apparent health (upon accidental or inappropriate ingestion [14,15], environmental consequences [8,16,17] and antibiotic resistance [18,19]. The study aims to determine and compare the perception and drug management regimen among high-density and low-density households in the absence of national guidelines for the disposal of unused and expired drugs in the study area.

Description Of The Study Area
The study took place in Ife Central Local Government Area (LGA). Ile-Ife is an ancient Yoruba city and the cradle of the Yoruba race. The city is in Osun East senatorial district in the southwest of Nigeria. The LGA has 11 wards and a total of 11 km 2 lies between latitudes 25 0 [20]. The LGA is densely populated by the Yoruba speaking people of southwestern Nigeria, in addition to other ethnic groups; such as Igbo and Hausa.

Study Design
The study is a comparative cross-sectional in nature and assessed the drugs handling and disposal practices of households in high-density and low-density settlements in the study area.

Target and Study Population
The study targeted all households in Ife Central LGA though studied selected households and interacted with women experienced in the drugs handling and disposal for at least one year.

Inclusion And Exclusion Criteria
Women who consented and have lived in the selected household for at least 12 months were enrolled into the study while those who were eligible consented and willing to participate in the study but incapacitated through sickness or mentally derailed were excluded from the study.

Sample Size
The study sample size for this study was calculated using the sample size formula: Where: n per group = sample size per group z a = level of con dence Standard normal variation for 95% con dence level, (Z a =1.96) z b = power of intense Standard normal variation for 80% con dence level, (Z b = 1.28) p 1 = prevalence of respondents that dispose of drugs with garbage (95%) in low-density settlements, (P 1 = 0.95 [15]. p 2 = prevalence of respondents that dispose of drugs with garbage (95%) in low-density settlements, (P 1 = 0.05 [15]. q 1 = 1 -p 1 hence q 1 = 0.05 (5 %) q 2 = 1 -p 2 hence q 2 = 0.15 (15 %) Page 5/34 n per group = 202 with 10% added for non-response, giving a total of 404 as the study minimum sample size.

Sampling Technique
The study applied a four-stage sampling technique. In stage one: the 11 political wards were strati ed into six urban and ve rural groups with two Wards selected from each group by simple random sampling technique.
In stage two, streets in each of the four wards were strati ed into high-density and low-density settlements with simple random sampling applied to select two from each group. Due to absence of the street sampling frame, systematic sampling selected even-numbered houses in selected streets from the proximate house at the street entrance until 26 households were approached, in each of the eight streets in stage three. In houses where there were multiple eligible households, simple random sampling was used to identify responding household among those available that met the inclusion criteria in stage four.

Data Collection
The study used a pretested, interviewer-administered semi-structured questionnaire that was designed in the English Language and translated to Yoruba and back-translated into English to ensure contents validity. The study questionnaire was however adapted with permission, from [9] and administered on respondents between January and February 2018.

Data Analysis
Data entry and analysis were done using the International business machine (IBM-Statistical package for social sciences (SPSS) version 20. Discrete variables were presented with tables and bar charts while the associations among related variables were determined by chi-square and at a p-value of < 0.05.

Outcome measures
Knowledge, attitude and perception on the handling and disposal of unused and expired drugs was a composite measure of 10, 13 and 23 variables, respectively. Correct responses were scored '1' and incorrect '0'. The median (IQR) values; respectively 7(6-8), 7(7-8) and 14 (13)(14)(15) for knowledge, attitude and perception were used to dichotomise ≥ median composite values into good/positive/high and those below the mean values as poor/negative/low ratings, respectively. The awareness of respondents on the protocol for disposal of unwholesome medicines was the binary, dependent variable while socio-demographic variables, including knowledge attitude, perception, and types of settlements, were independent variables in the binary logistic regression model. Similarly, the perception was a composite index of 23 variables.

Ethical Considerations
The study obtained ethical approval (IPHOAU/12/1008) from the research and ethics committee of the Institute of Public Health (IPH) of the Obafemi Awolowo University, in Nigeria. Also, permission and informed consent were respectively obtained from the head of the selected household and respondents. Responses were anonymised to preserve the con dentiality of respondents and personal identi ers were removed in summary data.

The study strengths and weaknesses
The study is cross-sectional in design and the respondents were randomly selected through multi-stage sampling technique to re ect their characteristics. Hence, the ndings can be generalised to the study population. In contrast, the study is prone to social desirability response bias, perhaps due to serial sematic order effects [21].

Socio-demographic characteristics of respondents
The study showed that the mean age of respondents in the LDS and HDS were respectively 36.1 ± 0.6 and 37.7 ± 0.7 years. Also, 82,8%, and 70.6%, respectively in the LDS and HDS were aged between 25 and 44 years. Most (82.5%) of the respondents belonged to the Yoruba ethnicity, with a similar trend in LDS (74.0%) and HDS (91.7%). Similarly, more than four out of ve respondents (82.8%) are married, distributed as 74.0% and 92.2%, respectively in LDS and HDS. The study also revealed that tertiary (50.0%) and secondary (49.0%) education predominates in LDS in contrast to secondary education (77.8%) in HDS, respectively (Table 1). A higher proportion of residents in LDS are civil servant (28.1%) when compared with those in HDS (3.9%) while higher proportions of residents in LDS (44.3%) and HDS (67.8%) were self-employed. At the same time, LDS and HDS was home to 87.5% and 56.1% of residents earning, respectively above and below the national minimum wage monthly, with the mean income for respondents in the LDS and HDS being ₦48,164 ± 2,896 and ₦18,405 ± 793, respectively. Besides, the study revealed that more respondents use the water closet toilet in the LDS (76.0%) than in the HDS (47.2%). Further, the modal household size in both LDS and HDS was 4 and strangely, 48.4% and 42,2% were rated poor and average, wealth-wise, respectively. Also, there were signi cant differences in all socio-demographic characteristics of respondents, between residents in LDS and HDS. (Table 1). Key: * = signi cant different between low-density and high-density settlements; + = Likely ratio chi square.

Drugs acquisition and duration of use characteristics
The health-seeking behaviour by respondents was healthcare facilities, made within three months of the study by a higher proportion of the study population, though not statistically signi cant between LDS and HDS. Also, a higher proportion of respondents, 82.2% and 68.3%, respectively in LDS and HDS visit pharmacy for drugs acquisition (    Key: * = signi cant different between low-density and high-density settlements; ++ = Likely ratio chi square. A  (Table 5). The abundance of unused and expired medicines in the study area   Key: * = signi cant different between low-density and high-density settlements; ++ = Likely ratio chi square.

Discussion
The paucity of guidelines for household management of unused and expired medications is being discussed in Nigeria and across the world. Current research endeavour is focussing on the emergence of sound disposal processes, which is a mirage in many developing countries. In Nigeria, medicines and other regulated products are labelled as 'unwholesome' when expired, improperly sealed and leaking, damaged, improperly stored, improperly labelled, counterfeit, substandard and adulterated, prohibited and unauthorized [22]. This made Asa [23] in 2011 and Michael et al. [24] in 2019 to assess the prevailing practices, respectively among households and community pharmacists in the disposal of expired drugs in Lagos and Anambra states in Nigeria. However, the national guidelines for the destruction of medicines and other regulated products were tailored for institutional-based consignments, while there was no provision or guide for management of UEMs from households [22]. Hence, the current study examined the abundance, household disposal practices and consequences of current management regimen for unused and expired medicines in the study area.

Socio-demographic characteristics
The current study purposively selected females in randomly selected households as respondents, who are the custodian of medicines, according to recognizance information in households, in contrast to Udo a et al. in Ghana where male and female community respondents were studied [9]; in Kabul, where most respondents were male and female university graduates [7], in Turkey, where more women reportedly kept unused drugs at home when compared to men [25], and in Nigeria, where the respondents were community-based pharmacists and involved both sexes [24].
In our study, most respondents were mid-adults in agreement with the respondents' age in the Kabul study [7] while most respondents were Christians, also in congruence with the study in Adigrat city, northern Ethiopia [26]. This is a productive population that is active in childbearing and innately tasked with caring for the wellbeing of the family. In this regard, a majority of respondents are married and had at least a secondary education in consonance with the ndings in Kabul, where 38.6% respondents had up to secondary education and 54.2% were university graduates [7]. Most respondents are married in LDS and HDS, though higher than those reported in Ethiopia (52.2%) [27] and more respondents had and use water closet toilet in the LDS (76.0%) than in the HDS (47.2%) settlements and can discard of liquid UEMs easily in their abode. Also, there were signi cant differences in all socio-demographic characteristics of respondents, between residents in LDS and HDS, indicating a disparity between the study groups.

Drugs acquisition and duration of use characteristics
Most respondents in LDS and HDS received drugs as part of treatment, though the inventory of drugs in respondents' homes was predominantly acquired through self-medication, for treatment of malaria and diarrhoea related ailments. This may be responsible for the observations by Barnett-Itzhaki et al. that large amounts of expired and unused medications accumulate in households [4]. It can, therefore, be hypothesized that people use, and complied with, a drug regimen, in most cases when prescribed as part of treatment by healthcare professionals with the tendency of those acquired through self-medication largely responsible for UEMs at the household level, as observed in Indonesia [28]. The abundance of UEMs in homes was due to non-compliance (56.8%) with the prescribed drug use regimen, due to feeling of recovery and the emergence of side effects [28][29][30]. This observation was consistent with the study ndings in Ethiopia where mostly due to recovery/disappearance of disease symptoms in most cases [27].

Knowledge of expiry and disposal of expired and unused medication
For drugs, compliance with medicines safety protocol is germane to keep the active pharmaceutical ingredients (API) active within their shelf life. Some medicines are to be kept active at a threshold of weather conditions. However, many households and users are ignorant of some stringent conditions to keep the API active. According to Laitmeyer and Adhoch, the United States Food and Drug Administration's (USFDA) de ned expiry date (designated by the manufacturers) is "the date placed on the container/labels of an API designating the time during which the API is expected to remain within established shelf-life speci cations if stored under de ned conditions and after which it should not be used" [31]. This has become worse with climate change, with environmental conditions exceeding the usual cold and warm temperatures, which also is expected to in uence the API. Besides, knowledge has been mooted as in uencing attitude and practice, though previous studies posited that good knowledge and positive attitude may not translate to good behaviour [15,32].
Most respondents are aware of medicines use instructions by weight and age prescriptions and knew that drugs are poisons and should be handled with care across the two study domains, as observed by Ruhoy and Daughton [34] and Verlicchi et al. [35] study ndings. Most drugs sachets lack disposal instructions, a limitation to acquiring sound disposal strategies and this did not stop respondents from recognising drugs as poison when either abused or ignorantly disposed of. Despite most respondents knowing that they have expiry dates, they believed that they can be used after expiry without adverse consequences while a few knew disposing of UEMs with wastes portends danger to human and the environment.
Most respondents in LDS have good knowledge in contrast to those in HDS where a majority has poor knowledge. This is rare in literature and contrast to previous studies [26,27,36,37]. This herald the signi cant differences in knowledge between respondents in HDS and LDS. Besides, most respondents in the current study demonstrated good knowledge, in agreement with previous studies from Ethiopia, New Zealand and Turkey [26,27,37,38], especially respondents in LDS in contrast to those in HDS where a majority has poor knowledge, in congruence with a study in Kenya [39], perhaps due to diversity in their socio-demographic characteristics. In the study area, sound UEMs management practice goes beyond the capacity of the households due to absence of necessary supportive mechanism and giving people information does not make them change, in any case.

Attitude on expiry and disposal of expired and unused medication
The general protocol holds among the respondents that medicines should be acquired based on doctors' prescription, as evident in the study. Besides, however, self-medication, through the purchase of medicines over the counter was also widely reported, especially among people in HDS. This situation was deepened since anyone can acquire medicines, without doctor's prescription in the study area, due to laxity in control and enforcement of extant national laws, perhaps to the about 90-220 minutes of wait-time associated with hospital visits by the sick for consultations, examinations and medicines acquisitions [40][41][42][43][44], apart from the non-availability of several essential medicines [45], expected to be provided by the National health insurance scheme in accredited healthcare facilities in Nigeria [46]. These might also be the reason for the increasing prevalence of NAFDAC licenced and unapproved herbal formulations.
Medicines expiry is the date provided on them that guarantees their full potency and safety under good manufacturing practices and several of them, such as vaccine vials, insulin and nitro-glycerin degenerate on expiry [47,48]. Our study revealed that many households con rmed medicines expiry on prescription and OTC drugs, as previously reported [7,9,25,28]. This could be attributed to the awareness created over the years on the need to ensure that medicines are still within the expiry dates before use. However, the expected medicines keeping conditions may be compromised in many patent medicine outlets, due to poor compliance and enforcement by responsible agencies. In agreement with previous studies, households keep medicines home [7,25]. and believe that such should be disposed of when expired. This is mostly supported for selfmedication in terms of emergency sickness and medication uses. The respondents had a positive attitude and high perception ratings, irrespective of the settlement area. This also agrees with ndings in Brazil [49] and Ethiopia [26,27].  [26] in Ethiopia where analgesics and antibiotics were highest in homes. The changing climate and illnesses endemicity could explain drugs abundance dynamics [23] and Nigeria tropical climate, with malaria being endemic could explain the abundance of antimalaria drugs in homes [50,51]. The availability of medicines in households might be due to a lack of a formal system for drug take-back policy and system which portends disposal challenges, especially when expired [52].
Strategy for disposing of unused and expired medicines by households A few respondents have seen advertorials on the safe management of damaged and expired medicines through the news and electronic media, indicting a poor public awareness on disposal guidelines for unused, damaged and expired medicines [26,27,53]. In another study, respondents attested to paucity of information on disposal of UEMs [28,54]. Just as the management of healthcare wastes are not regulated in many countries at the household level [55], there is no protocol either by NAFDAC or NESREA to guide home management of damaged and expired medications in Nigeria, and thus, contributing to the ignorance of households in LDS and HDSs in the study area. These ndings agree with previous studies in Australia [28], Nigeria [23] and in systematic reviews which reported similar ndings in the USA, New Zealand, Bangladesh, Malta and Ireland [37,53], with greater consequences in countries with poor solid waste management systems were reported. These studies con rmed the 'absence of a global comprehensive and binding approach', that should encourage a safe medication disposal strategy [4,28].

Perceived consequences of indiscriminate disposal of unused and expired medicines
The cradle-to-grave responsibility for medicines and their impact on the global environment is gaining attention [55], especially due to the recognised and perceived environmental and public health consequences associated with the disposal of UEMs. This made some respondents to respectively considered accidental ingestion of leftover and expired medicines, land and water pollution and drugs toxicity, though there was a signi cant difference between LDS and HDS (p = 0001). The reported consequences were in agreement with previous studies in Nigeria [24,56] and Ethiopia [27] and Malaysia [54], and in systematic reviews [52]. There were trace concentrations of medicine APIs in conventional drinking water resources and land lls leachates [58]. Other consequences include accidental medicine poisonings, diversion/repackaging of UEMs for illicit use and antibiotic resistance, all of which impose socio-economic, human health and ethical burdens at the population level [53]. This was, however, at variance with ignorance reported in Indonesia by 53.1% of households that unsafe medication disposal practices could harm the environment and population health [28], and are rarely removed in water and wastewater treatment plants [4].
The awareness of respondents on the disposal of UEMs was strongly predicted by marital status, occupation, and knowledge. However, this outcome needs to be interpreted with caution, since the weighting was not applied to detect the true effects of these covariates and on awareness of respondents on the disposal of used and expired medications.

Conclusions
There was unwholesome disposal of UEMs between residents with solid wastes in low-density and highdensity settlements. Respondents good knowledge and positive attitudes contrasted to poor UEMs disposal practice. Most of the drugs in households were antimalaria and analgesics with solid and liquid medicines disposed of in most cases with solid wastes. The perceived consequences of the current disposal practice include accidental ingestion, land and water pollution and drugs toxicity. Therefore, appropriate legislation should herald sound, and incentive-driven, UEMs return for disposal drop-off systems to designated premises.
This should be aided by compliance assessment to drive its recovery and alleviate the negative consequences of current disposal practices in Nigeria.

Abbreviations
APIs -Active pharmaceutical ingredients  Perceived consequences of indiscriminate disposal of unused and expired medicines