Prevalence and Patterns of Polypharmacy and Potential Drug-Drug Interactions Among Older Adults Attending a Primary Care Center in Iran: A Cross-Sectional Study

Prevalence and Patterns of Polypharmacy and Potential Drug-Drug Interactions Among Older Adults Attending a Primary Care Center in Iran: A Cross-Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and Patterns of Polypharmacy and Potential Drug-Drug Interactions Among Older Adults Attending a Primary Care Center in Iran: A Cross-Sectional Study Mahfam Alijaniha, Mahdin Alijaniha, Mahdi Mirzaalimohammadi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8311133/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Polypharmacy, a critical geriatric syndrome, is associated with adverse outcomes like drug-drug interactions (DDIs) and hospitalizations. In Iran, fragmented healthcare may exacerbate its prevalence among older adults. This study aimed to investigate polypharmacy prevalence, predictors, and potential DDI profiles in Iranian older adults in primary care. Methods This retrospective cross-sectional study analyzed electronic health records of patients aged ≥ 65 from an Iranian primary care center. Data included demographics, chronic medications, and potential DDIs identified via Lexicomp®. Polypharmacy and hyper-polypharmacy were defined as 5–9 and ≥ 10 medications, respectively. Statistical analyses included descriptive statistics, chi-square tests, and binary logistic regression. A detailed qualitative DDI analysis was performed. Results The analysis included 230 older adults (mean age 73.5 ± 6.2 years). Polypharmacy prevalence was 68.3%, with hyper-polypharmacy at 22.2%. Each year of age increased polypharmacy odds by 10% (aOR = 1.10, 95% CI: 1.05–1.16, p < 0.001). Gender showed no significant association. Analysis identified 189 unique potential DDI pairs. The most frequent/severe interactions involved Aspirin-NSAIDs and cardiovascular-renal drugs (e.g., ACE inhibitors with potassium-sparing diuretics). Conclusion Polypharmacy and hyper-polypharmacy are highly prevalent among Iranian older adults in primary care and are strongly age-dependent. The high burden of potentially severe DDIs underscores the urgent need for systematic medication reviews and pharmacist-led interventions to optimize prescribing and enhance medication safety in this vulnerable population. Polypharmacy Drug-Drug Interactions Older Adults Aged Primary Health Care Medication Safety Iran Figures Figure 1 Figure 2 Background Polypharmacy, typically defined as the concurrent use of five or more medications, poses a significant global public health challenge, particularly for aging populations [ 1 ]. Recognized as a geriatric syndrome, it is strongly associated with increased risks of adverse drug reactions, harmful drug-drug interactions (DDIs), hospitalizations, and mortality [ 2 ]. The clinical and economic burdens are substantial, straining healthcare systems and compromising older adults’ quality of life [ 3 ]. Globally, polypharmacy prevalence is high and rising, with recent systematic reviews indicating rates of 35–50% among community-dwelling older adults and exceeding 70% in clinical settings [ 4 , 5 ]. In Iran, similar alarming trends are reported, with studies showing polypharmacy rates between 40% and 65% in elderly populations, often involving cardiovascular, analgesic, and gastrointestinal agents [ 6 , 7 ]. This high prevalence occurs within a healthcare context characterized by challenges such as insufficient geriatric care infrastructure, poor care coordination, and easy access to medications, all contributing to potentially inappropriate prescribing [ 8 , 9 ]. While the prevalence of polypharmacy in Iran is documented, a critical evidence gap exists regarding the detailed, clinically-actionable profiles of associated medication safety risks, specifically DDIs, in the older adult population within routine primary care. Most studies focus on quantifying medication numbers, with limited in-depth analysis of DDI patterns, severity, and likelihood. A granular understanding of which specific drug pairs most frequently contribute to high-risk interactions is essential for developing targeted deprescribing strategies and clinical guidelines tailored to this demographic [ 10 ]. This study aimed to address this gap by conducting a comprehensive analysis focused exclusively on older adults (≥ 65 years). The objectives were threefold: (1) to determine the prevalence of polypharmacy and hyper-polypharmacy, (2) to identify key demographic predictors, and (3) to perform a detailed characterization of potential DDI patterns—including the most common and high-risk drug pairs, their severity, and clinical implications—within a real-world Iranian primary care setting. Methods Study Design and Setting A retrospective cross-sectional study was conducted using de-identified electronic health records from a primary care center affiliated with the Iranian Social Security Organization. The study period covered the first six months of the Iranian calendar year 1403 (March 21 to September 21, 2024). Study Population and Eligibility Criteria The initial dataset included all adult patient records. For this analysis, the inclusion criterion was age 65 years or older. Exclusion criteria were: (1) pregnancy, (2) incomplete medication lists or key demographic data, and (3) lack of documented consent for research use of anonymized data per the clinic’s ethical protocol. The final analytical sample comprised 230 older adults. Data Collection and Variables Data were extracted using a standardized form: Demographics Age (continuous) and sex. Medication Use The total number of prescribed chronic medications per patient was counted from the active medication list. Chronic medications were defined as those prescribed for the ongoing management of a long-term condition (e.g., hypertension, diabetes, dyslipidemia). Over-the-counter medications were excluded due to inconsistent documentation. Potential Drug-Drug Interactions (DDIs) Data on potential DDIs were extracted from the clinic’s integrated clinical decision support system, which utilized the Lexicomp® database. Extracted data for each flagged interaction included the specific drug pair, severity (categorized as Moderate or Severe), and likelihood (categorized as Possible, Probable, or Established). Definitions Polypharmacy Concurrent use of 5 to 9 chronic medications. Hyper-polypharmacy Concurrent use of 10 or more chronic medications. Primary Outcome : Polypharmacy status (binary: Yes/No). Statistical Analysis Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0. Descriptive statistics are presented as mean ± standard deviation (SD) for continuous variables and as frequencies (percentages) for categorical variables. Group comparisons employed independent samples t-tests for age and chi-square tests for sex distribution and prevalence rates. Binary logistic regression was used to identify factors independently associated with polypharmacy, calculating adjusted odds ratios (aORs) with 95% confidence intervals (CIs). A p-value < 0.05 was considered statistically significant. The DDI analysis was primarily qualitative and descriptive, focusing on the frequency, severity, and clinical nature of the most common interaction pairs. Ethical Considerations This study was approved by the Ethics Committee of Zanjan University of Medical Sciences (ethical code: ZUMS.REC.1394.322). The requirement for informed consent was waived due to the retrospective, anonymized nature of the data analysis. All procedures adhered to the ethical principles of the Declaration of Helsinki. Results Demographic and Clinical Characteristics Table 1 summarizes the characteristics of the 230 included older adults. The mean age was 73.5 ± 6.2 years, with a near-equal sex distribution (51.3% female). The mean number of chronic medications per patient was 6.1 ± 3.4. Patients with polypharmacy (≥ 5 drugs) were significantly older and had a higher mean medication count than the non-polypharmacy group (p < 0.001 for both). Sex distribution did not differ significantly between groups (p = 0.442). Table 1 Characteristics of the Study Population (Aged ≥ 65 Years) Characteristic Total (n = 230) Non-Polypharmacy (< 5 drugs) (n = 73) Polypharmacy (≥ 5 drugs) (n = 157) p-value Age (years), Mean ± SD 73.5 ± 6.2 70.2 ± 5.1 75.1 ± 5.8 < 0.001 Sex, n (%) 0.442 Male 112 (48.7%) 38 (52.1%) 74 (47.1%) Female 118 (51.3%) 35 (47.9%) 83 (52.9%) Number of Medications, Mean ± SD 6.1 ± 3.4 2.8 ± 1.2 8.2 ± 2.5 < 0.001 Prevalence of Polypharmacy The overall prevalence of polypharmacy (≥ 5 medications) was 68.3% (157/230). Of these, 46.1% (106/230) had standard polypharmacy (5–9 drugs), and 22.2% (51/230) had hyper-polypharmacy (≥ 10 drugs) (Fig. 1 ). Factors Associated with Polypharmacy Logistic regression confirmed that increasing age was a strong, independent predictor. For each one-year increase in age, the odds of polypharmacy increased by 10% (aOR = 1.10, 95% CI: 1.05–1.16, p < 0.001). Female sex was not a significant predictor (aOR = 1.21, 95% CI: 0.69–2.13, p = 0.506). A scatter plot illustrating the positive relationship between increasing age and the number of medications is presented in Fig. 2 . Analysis of Potential Drug-Drug Interactions (DDIs) The analysis identified 189 unique potential DDI pairs. Table 2 lists the five most frequent pairs. Table 2 Most Frequent Potential Drug-Drug Interaction Pairs Drug 1 Drug 2 Frequency (n) Most Common Severity Most Common Likelihood Aspirin 80 mg Ibuprofen 400 mg 18 Severe Probable Aspirin 80 mg Captopril 25 mg 15 Moderate Probable Aspirin 80 mg Indomethacin 25 mg 11 Severe Probable Captopril 25 mg Spironolactone 25 mg 9 Severe Very Probable Atorvastatin 20 mg Diltiazem 60 mg 8 Moderate Very Probable Severity and Likelihood Of the 189 interactions, 88 (46.6%) were classified as 'Severe' and 101 (53.4%) as 'Moderate'. Regarding likelihood, 55.0% were 'Probable', 28.6% 'Very Probable', and 16.4% 'Established'. Key Patterns Aspirin 80 mg was the most central drug. Its interactions with NSAIDs (Ibuprofen, Indomethacin) were consistently 'Severe', primarily signaling a heightened risk of gastrointestinal bleeding. High-risk cardiovascular-renal interactions, such as between ACE inhibitors (Captopril) and potassium-sparing diuretics (Spironolactone), were also common and predominantly 'Severe'/'Very Probable', highlighting risks for hyperkalemia and renal impairment. Discussion This study provides a focused analysis of polypharmacy and associated DDI risks exclusively among older adults (≥ 65 years) in an Iranian primary care setting. The key finding is an alarmingly high prevalence of polypharmacy (68.3%) and hyper-polypharmacy (22.2%), which substantially exceeds rates reported in many community-based international studies [ 4 , 11 ] and aligns with higher estimates from other clinical settings in Iran and the region [ 7 , 12 ]. This underscores polypharmacy as a paramount and escalating concern in geriatric care in Iran. The powerful, independent association between advancing age and polypharmacy is consistent with global geriatric literature and reflects the cumulative burden of multimorbidity requiring complex pharmacotherapy [ 13 , 14 ]. The lack of significant association with sex in our cohort suggests that in later life, clinical need driven by comorbidity burden, rather than sex per se, is the primary driver of multiple medication use [ 15 ]. The detailed DDI analysis reveals a substantial medication safety burden. The high frequency of severe Aspirin-NSAID interactions points to a common, preventable risk for gastrointestinal complications. This pattern may be exacerbated by the over-the-counter availability of NSAIDs in Iran and a lack of coordinated care among multiple prescribers, highlighting the need for integrated medication records [ 16 ]. Similarly, the prevalence of interactions affecting the cardiovascular-renal axis (e.g., ACE inhibitors with potassium-sparing diuretics) highlights a critical area for clinical vigilance, given the high baseline risk of renal impairment and electrolyte disturbances in older adults [ 17 ]. These patterns indicate that while polypharmacy is often clinically indicated for multimorbidity, it is frequently accompanied by unaddressed or inadequately managed interaction risks [ 18 ]. Our findings have immediate implications for practice and policy. They argue compellingly for the mandatory integration of structured medication reviews led by clinical pharmacists within primary care geriatric services in Iran [ 19 , 20 ]. Such reviews should prioritize deprescribing high-risk drug pairs, particularly antithrombotics with NSAIDs and renally-active combinations. For policymakers, these results underscore the urgent need to develop and disseminate national evidence-based guidelines for medication management in older adults with multimorbidity and to strengthen geriatric training for primary care providers [ 21 , 22 ]. Impact Statement This study reveals an alarmingly high rate of polypharmacy and severe drug interactions among Iranian older adults in primary care. It provides concrete, data-driven evidence to advocate for the mandatory implementation of pharmacist-led medication review services within geriatric care. The findings offer a specific target list of high-risk drug pairs (e.g., Aspirin-NSAIDs, ACEi-potassium-sparing diuretics) for clinicians and policymakers to prioritize in deprescribing initiatives, clinical guideline development, and educational interventions aimed at optimizing medication safety for Iran's aging population. Limitations This study has limitations. Its cross-sectional design precludes causal inference. The single-center setting may limit generalizability to other regions or healthcare systems in Iran. Data on over-the-counter medication use and clinical outcomes (e.g., hospitalizations due to adverse drug events) were unavailable, potentially leading to underestimation. The DDI data reflect potential interactions flagged by a clinical decision support system (Lexicomp®) and do not confirm actual adverse events. Conclusion Polypharmacy and hyper-polypharmacy are exceedingly common among older adults in this Iranian primary care population and are strongly linked to increasing age. The concomitant high burden of potentially severe drug-drug interactions presents a clear and present danger to medication safety. These results mandate a systematic shift towards proactive, pharmacist-enhanced medication management and tailored deprescribing initiatives specifically designed for the geriatric population in Iran to mitigate risks and improve health outcomes. Abbreviations DDI Drug-Drug Interaction aOR Adjusted Odds Ratio CI Confidence Interval SD Standard Deviation NSAID Non-Steroidal Anti-Inflammatory Drug ACEi Angiotensin-Converting Enzyme inhibitor. Declarations Ethics approval and consent to participate Approved by the Ethics Committee of Zanjan University of Medical Sciences (ZUMS.REC.1394.322). Informed consent was waived for this retrospective analysis of anonymized data. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Funding This research received no specific grant from any funding agency. Author Contribution MA (Mahfam Alijaniha): Conceptualization, Methodology, Formal Analysis, Writing – Original Draft. MA (Mahdin Alijaniha): Data Curation, Investigation, Writing – Review & Editing.MM (Mahdi Mirzaalimohammadi): Validation, Resources, Writing – Review & Editing. All authors read and approved the final manuscript. Acknowledgements Not applicable. 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Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 17 Jan, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers invited by journal 08 Jan, 2026 Editor invited by journal 10 Dec, 2025 Editor assigned by journal 09 Dec, 2025 Submission checks completed at journal 09 Dec, 2025 First submitted to journal 08 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8311133","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":573176056,"identity":"4cd60894-527b-4aab-9702-f2ce2838fad0","order_by":0,"name":"Mahfam 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2","display":"","copyAsset":false,"role":"figure","size":107245,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing the relationship between patient age and number of medications among older adults (N=230).\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8311133/v1/f7cfdb4cafad97fb5c96ac67.jpg"},{"id":100390521,"identity":"ae8d1271-bfe3-4194-aae8-0c01fd34b9cb","added_by":"auto","created_at":"2026-01-16 11:21:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1024799,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8311133/v1/0509ff31-5852-4a50-8396-c629ffc09d87.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and Patterns of Polypharmacy and Potential Drug-Drug Interactions Among Older Adults Attending a Primary Care Center in Iran: A Cross-Sectional Study","fulltext":[{"header":"Background","content":"\u003cp\u003ePolypharmacy, typically defined as the concurrent use of five or more medications, poses a significant global public health challenge, particularly for aging populations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Recognized as a geriatric syndrome, it is strongly associated with increased risks of adverse drug reactions, harmful drug-drug interactions (DDIs), hospitalizations, and mortality [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The clinical and economic burdens are substantial, straining healthcare systems and compromising older adults\u0026rsquo; quality of life [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGlobally, polypharmacy prevalence is high and rising, with recent systematic reviews indicating rates of 35\u0026ndash;50% among community-dwelling older adults and exceeding 70% in clinical settings [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In Iran, similar alarming trends are reported, with studies showing polypharmacy rates between 40% and 65% in elderly populations, often involving cardiovascular, analgesic, and gastrointestinal agents [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This high prevalence occurs within a healthcare context characterized by challenges such as insufficient geriatric care infrastructure, poor care coordination, and easy access to medications, all contributing to potentially inappropriate prescribing [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile the prevalence of polypharmacy in Iran is documented, a critical evidence gap exists regarding the detailed, clinically-actionable profiles of associated medication safety risks, specifically DDIs, in the older adult population within routine primary care. Most studies focus on quantifying medication numbers, with limited in-depth analysis of DDI patterns, severity, and likelihood. A granular understanding of which specific drug pairs most frequently contribute to high-risk interactions is essential for developing targeted deprescribing strategies and clinical guidelines tailored to this demographic [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to address this gap by conducting a comprehensive analysis focused exclusively on older adults (\u0026ge;\u0026thinsp;65 years). The objectives were threefold: (1) to determine the prevalence of polypharmacy and hyper-polypharmacy, (2) to identify key demographic predictors, and (3) to perform a detailed characterization of potential DDI patterns\u0026mdash;including the most common and high-risk drug pairs, their severity, and clinical implications\u0026mdash;within a real-world Iranian primary care setting.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Setting\u003c/h2\u003e \u003cp\u003e A retrospective cross-sectional study was conducted using de-identified electronic health records from a primary care center affiliated with the Iranian Social Security Organization. The study period covered the first six months of the Iranian calendar year 1403 (March 21 to September 21, 2024).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Population and Eligibility Criteria\u003c/h3\u003e\n\u003cp\u003eThe initial dataset included all adult patient records. For this analysis, the inclusion criterion was age 65 years or older. Exclusion criteria were: (1) pregnancy, (2) incomplete medication lists or key demographic data, and (3) lack of documented consent for research use of anonymized data per the clinic\u0026rsquo;s ethical protocol. The final analytical sample comprised 230 older adults.\u003c/p\u003e\n\u003ch3\u003eData Collection and Variables\u003c/h3\u003e\n\u003cp\u003eData were extracted using a standardized form:\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eDemographics\u003c/strong\u003e \u003cp\u003eAge (continuous) and sex.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eMedication Use\u003c/strong\u003e \u003cp\u003eThe total number of prescribed chronic medications per patient was counted from the active medication list. Chronic medications were defined as those prescribed for the ongoing management of a long-term condition (e.g., hypertension, diabetes, dyslipidemia). Over-the-counter medications were excluded due to inconsistent documentation.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003ePotential Drug-Drug Interactions (DDIs)\u003c/strong\u003e \u003cp\u003eData on potential DDIs were extracted from the clinic\u0026rsquo;s integrated clinical decision support system, which utilized the \u003cb\u003eLexicomp\u0026reg;\u003c/b\u003e database. Extracted data for each flagged interaction included the specific drug pair, severity (categorized as Moderate or Severe), and likelihood (categorized as Possible, Probable, or Established).\u003c/p\u003e \u003c/p\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003e \u003cstrong\u003ePolypharmacy\u003c/strong\u003e \u003cp\u003eConcurrent use of 5 to 9 chronic medications.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eHyper-polypharmacy\u003c/strong\u003e \u003cp\u003eConcurrent use of 10 or more chronic medications.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePrimary Outcome\u003c/b\u003e: Polypharmacy status (binary: Yes/No).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eData were analyzed using IBM SPSS Statistics for Windows, Version 26.0. Descriptive statistics are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables and as frequencies (percentages) for categorical variables. Group comparisons employed independent samples t-tests for age and chi-square tests for sex distribution and prevalence rates. Binary logistic regression was used to identify factors independently associated with polypharmacy, calculating adjusted odds ratios (aORs) with 95% confidence intervals (CIs). A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. The DDI analysis was primarily qualitative and descriptive, focusing on the frequency, severity, and clinical nature of the most common interaction pairs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEthical Considerations\u003c/h2\u003e \u003cp\u003e This study was approved by the Ethics Committee of Zanjan University of Medical Sciences (ethical code: ZUMS.REC.1394.322). The requirement for informed consent was waived due to the retrospective, anonymized nature of the data analysis. All procedures adhered to the ethical principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and Clinical Characteristics\u003c/h2\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the characteristics of the 230 included older adults. The mean age was 73.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 years, with a near-equal sex distribution (51.3% female). The mean number of chronic medications per patient was 6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4. Patients with polypharmacy (\u0026ge;\u0026thinsp;5 drugs) were significantly older and had a higher mean medication count than the non-polypharmacy group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for both). Sex distribution did not differ significantly between groups (p\u0026thinsp;=\u0026thinsp;0.442).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of the Study Population (Aged\u0026thinsp;\u0026ge;\u0026thinsp;65 Years)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;230)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-Polypharmacy (\u0026lt;\u0026thinsp;5 drugs) (n\u0026thinsp;=\u0026thinsp;73)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePolypharmacy (\u0026ge;\u0026thinsp;5 drugs) (n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years), Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e75.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.442\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e112 (48.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (52.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (51.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (47.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e83 (52.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of Medications, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003ePrevalence of Polypharmacy\u003c/h2\u003e \u003cp\u003eThe overall prevalence of polypharmacy (\u0026ge;\u0026thinsp;5 medications) was 68.3% (157/230). Of these, 46.1% (106/230) had standard polypharmacy (5\u0026ndash;9 drugs), and 22.2% (51/230) had hyper-polypharmacy (\u0026ge;\u0026thinsp;10 drugs) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eFactors Associated with Polypharmacy\u003c/h2\u003e \u003cp\u003eLogistic regression confirmed that increasing age was a strong, independent predictor. For each one-year increase in age, the odds of polypharmacy increased by 10% (aOR\u0026thinsp;=\u0026thinsp;1.10, 95% CI: 1.05\u0026ndash;1.16, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Female sex was not a significant predictor (aOR\u0026thinsp;=\u0026thinsp;1.21, 95% CI: 0.69\u0026ndash;2.13, p\u0026thinsp;=\u0026thinsp;0.506). A scatter plot illustrating the positive relationship between increasing age and the number of medications is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of Potential Drug-Drug Interactions (DDIs)\u003c/h2\u003e \u003cp\u003eThe analysis identified 189 unique potential DDI pairs. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e lists the five most frequent pairs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMost Frequent Potential Drug-Drug Interaction Pairs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrug 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDrug 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency (n)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMost Common Severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMost Common Likelihood\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin 80 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIbuprofen 400 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProbable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin 80 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCaptopril 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProbable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAspirin 80 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIndomethacin 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProbable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaptopril 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSpironolactone 25 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVery Probable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtorvastatin 20 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiltiazem 60 mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eVery Probable\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eSeverity and Likelihood\u003c/strong\u003e \u003cp\u003eOf the 189 interactions, 88 (46.6%) were classified as 'Severe' and 101 (53.4%) as 'Moderate'. Regarding likelihood, 55.0% were 'Probable', 28.6% 'Very Probable', and 16.4% 'Established'.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eKey Patterns\u003c/strong\u003e \u003cp\u003eAspirin 80 mg was the most central drug. Its interactions with NSAIDs (Ibuprofen, Indomethacin) were consistently 'Severe', primarily signaling a heightened risk of gastrointestinal bleeding. High-risk cardiovascular-renal interactions, such as between ACE inhibitors (Captopril) and potassium-sparing diuretics (Spironolactone), were also common and predominantly 'Severe'/'Very Probable', highlighting risks for hyperkalemia and renal impairment.\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study provides a focused analysis of polypharmacy and associated DDI risks exclusively among older adults (\u0026ge;\u0026thinsp;65 years) in an Iranian primary care setting. The key finding is an alarmingly high prevalence of polypharmacy (68.3%) and hyper-polypharmacy (22.2%), which substantially exceeds rates reported in many community-based international studies [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and aligns with higher estimates from other clinical settings in Iran and the region [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This underscores polypharmacy as a paramount and escalating concern in geriatric care in Iran.\u003c/p\u003e \u003cp\u003eThe powerful, independent association between advancing age and polypharmacy is consistent with global geriatric literature and reflects the cumulative burden of multimorbidity requiring complex pharmacotherapy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The lack of significant association with sex in our cohort suggests that in later life, clinical need driven by comorbidity burden, rather than sex per se, is the primary driver of multiple medication use [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe detailed DDI analysis reveals a substantial medication safety burden. The high frequency of severe Aspirin-NSAID interactions points to a common, preventable risk for gastrointestinal complications. This pattern may be exacerbated by the over-the-counter availability of NSAIDs in Iran and a lack of coordinated care among multiple prescribers, highlighting the need for integrated medication records [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Similarly, the prevalence of interactions affecting the cardiovascular-renal axis (e.g., ACE inhibitors with potassium-sparing diuretics) highlights a critical area for clinical vigilance, given the high baseline risk of renal impairment and electrolyte disturbances in older adults [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. These patterns indicate that while polypharmacy is often clinically indicated for multimorbidity, it is frequently accompanied by unaddressed or inadequately managed interaction risks [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur findings have immediate implications for practice and policy. They argue compellingly for the mandatory integration of structured medication reviews led by clinical pharmacists within primary care geriatric services in Iran [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Such reviews should prioritize deprescribing high-risk drug pairs, particularly antithrombotics with NSAIDs and renally-active combinations. For policymakers, these results underscore the urgent need to develop and disseminate national evidence-based guidelines for medication management in older adults with multimorbidity and to strengthen geriatric training for primary care providers [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eImpact Statement\u003c/h2\u003e \u003cp\u003eThis study reveals an alarmingly high rate of polypharmacy and severe drug interactions among Iranian older adults in primary care. It provides concrete, data-driven evidence to advocate for the mandatory implementation of pharmacist-led medication review services within geriatric care. The findings offer a specific target list of high-risk drug pairs (e.g., Aspirin-NSAIDs, ACEi-potassium-sparing diuretics) for clinicians and policymakers to prioritize in deprescribing initiatives, clinical guideline development, and educational interventions aimed at optimizing medication safety for Iran's aging population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has limitations. Its cross-sectional design precludes causal inference. The single-center setting may limit generalizability to other regions or healthcare systems in Iran. Data on over-the-counter medication use and clinical outcomes (e.g., hospitalizations due to adverse drug events) were unavailable, potentially leading to underestimation. The DDI data reflect \u003cem\u003epotential\u003c/em\u003e interactions flagged by a clinical decision support system (Lexicomp\u0026reg;) and do not confirm actual adverse events.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePolypharmacy and hyper-polypharmacy are exceedingly common among older adults in this Iranian primary care population and are strongly linked to increasing age. The concomitant high burden of potentially severe drug-drug interactions presents a clear and present danger to medication safety. These results mandate a systematic shift towards proactive, pharmacist-enhanced medication management and tailored deprescribing initiatives specifically designed for the geriatric population in Iran to mitigate risks and improve health outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eDDI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eDrug-Drug Interaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaOR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdjusted Odds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eStandard Deviation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNSAID\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNon-Steroidal Anti-Inflammatory Drug\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACEi\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAngiotensin-Converting Enzyme inhibitor.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e Approved by the Ethics Committee of Zanjan University of Medical Sciences (ZUMS.REC.1394.322). Informed consent was waived for this retrospective analysis of anonymized data.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCompeting interests\u003c/strong\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis research received no specific grant from any funding agency.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eMA (Mahfam Alijaniha): Conceptualization, Methodology, Formal Analysis, Writing \u0026ndash; Original Draft. MA (Mahdin Alijaniha): Data Curation, Investigation, Writing \u0026ndash; Review \u0026amp; Editing.MM (Mahdi Mirzaalimohammadi): Validation, Resources, Writing \u0026ndash; Review \u0026amp; Editing. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMasnoon N, Shakib S, Kalisch-Ellett L, et al. What is polypharmacy? A systematic review of definitions. BMC Geriatr. 2017;17(1):230.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePazan F, Wehling M. Polypharmacy in older adults: a narrative review of definitions, epidemiology and consequences. Eur Geriatr Med. 2021;12(3):443\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorgan SG, Hunt J, Rioux J, et al. Frequency and cost of potentially inappropriate prescribing for older adults: a cross-sectional study. 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BMJ Open. 2015;5(12):e009235.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanlon JT, Perera S, Newman AB, et al. Potential drug-drug and drug-disease interactions in well-functioning community-dwelling older adults. J Clin Pharm Ther. 2017;42(2):228\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eO\u0026rsquo;Mahony D, O\u0026rsquo;Sullivan D, Byrne S, et al. STOPP/START criteria for potentially inappropriate prescribing in older people: version 3. Eur Geriatr Med. 2023;14(4):625\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe American Geriatrics Society Beers Criteria\u0026reg; Update Expert Panel. The American Geriatrics Society 2023 updated AGS Beers Criteria\u0026reg; for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlshammari TM, Alhindi SA, Alrashidi MN, et al. Polypharmacy and medication-related problems among geriatric patients in primary healthcare settings in Saudi Arabia. Saudi Pharm J. 2023;31(5):698\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKua KP, Saw PS, Lee SWH. Attitudes and beliefs of physicians and pharmacists about deprescribing: a systematic review. Br J Clin Pharmacol. 2022;88(3):952\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Polypharmacy, Drug-Drug Interactions, Older Adults, Aged, Primary Health Care, Medication Safety, Iran","lastPublishedDoi":"10.21203/rs.3.rs-8311133/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8311133/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePolypharmacy, a critical geriatric syndrome, is associated with adverse outcomes like drug-drug interactions (DDIs) and hospitalizations. In Iran, fragmented healthcare may exacerbate its prevalence among older adults. This study aimed to investigate polypharmacy prevalence, predictors, and potential DDI profiles in Iranian older adults in primary care.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective cross-sectional study analyzed electronic health records of patients aged\u0026thinsp;\u0026ge;\u0026thinsp;65 from an Iranian primary care center. Data included demographics, chronic medications, and potential DDIs identified via Lexicomp\u0026reg;. Polypharmacy and hyper-polypharmacy were defined as 5\u0026ndash;9 and \u0026ge;\u0026thinsp;10 medications, respectively. Statistical analyses included descriptive statistics, chi-square tests, and binary logistic regression. A detailed qualitative DDI analysis was performed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe analysis included 230 older adults (mean age 73.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 years). Polypharmacy prevalence was 68.3%, with hyper-polypharmacy at 22.2%. Each year of age increased polypharmacy odds by 10% (aOR\u0026thinsp;=\u0026thinsp;1.10, 95% CI: 1.05\u0026ndash;1.16, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Gender showed no significant association. Analysis identified 189 unique potential DDI pairs. The most frequent/severe interactions involved Aspirin-NSAIDs and cardiovascular-renal drugs (e.g., ACE inhibitors with potassium-sparing diuretics).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePolypharmacy and hyper-polypharmacy are highly prevalent among Iranian older adults in primary care and are strongly age-dependent. The high burden of potentially severe DDIs underscores the urgent need for systematic medication reviews and pharmacist-led interventions to optimize prescribing and enhance medication safety in this vulnerable population.\u003c/p\u003e","manuscriptTitle":"Prevalence and Patterns of Polypharmacy and Potential Drug-Drug Interactions Among Older Adults Attending a Primary Care Center in Iran: A Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 00:06:50","doi":"10.21203/rs.3.rs-8311133/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-01-17T11:17:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300026551825417205880305801360374808431","date":"2026-01-12T10:28:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-08T13:31:06+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-10T07:01:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-10T04:38:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-10T04:37:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2025-12-08T21:27:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d91c0e0b-401f-445c-9aa7-ffcbe805431a","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-16T00:06:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 00:06:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8311133","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8311133","identity":"rs-8311133","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}