European Journal of Cardiovascular Medicine

The global rise in life expectancy has led to a rapidly expanding elderly population, who are disproportionately affected by multiple chronic conditions such as hypertension, diabetes, arthritis, and cardiovascular diseases. These conditions often necessitate complex pharmacological regimens, resulting in polypharmacy, commonly defined as the concurrent use of five or more medications [1,3]. While polypharmacy may be clinically justified, it significantly increases the risk of adverse drug reactions (ADRs), drug-drug interactions, therapeutic duplication, non-adherence, and higher healthcare utilization [1,4].

Age-related physiological changes, including altered drug absorption, reduced hepatic metabolism, impaired renal clearance, and changes in body fat and lean mass, further compound the risk of ADRs in older adults [2,5]. Studies have shown that the elderly are at a markedly higher risk for serious ADRs that can result in hospital admissions, prolonged hospital stays, functional decline, and increased morbidity and mortality [5]. In a Ugandan cohort, for example, advanced age and polypharmacy were strong predictors of hospital-acquired ADRs [7].

Despite these well-documented risks, ADRs in the elderly remain under-recognized and underreported, particularly in resource-constrained or overburdened healthcare settings [6]. This highlights a critical need for systematic evaluation and monitoring of medication safety in older populations.

Understanding the incidence, nature, severity, and preventability of ADRs among elderly patients on polypharmacy is crucial for improving prescribing practices, guiding timely deprescribing, and developing safer geriatric pharmacotherapy protocols [3,6].

This prospective observational study was undertaken to evaluate the incidence and pattern of ADRs in elderly patients receiving polypharmacy in a tertiary care hospital. The study also aimed to assess the severity, causality, and preventability of these ADRs using standard pharmacovigilance tools, thereby contributing to the growing evidence base required for safer geriatric pharmacotherapy.

Study Design and Setting:
A prospective observational study was conducted in the Department of General Medicine at Government Medical College (GMC), Rajamahendravaram, over a six-month period from May 2023 to October 2023. The study also incorporated data from surrounding private hospitals to ensure comprehensive coverage of the patient population in the region.

Study Population:
The study included elderly patients aged 60 years and above who were admitted to the medicine wards and receiving polypharmacy, defined as the concurrent use of five or more medications. Patients were enrolled after obtaining informed consent.

Inclusion Criteria:

Age ≥60 years

Hospitalized patients receiving ≥5 medications during admission

Willingness to participate in the study

Exclusion Criteria:

Patients with terminal illnesses or those receiving palliative care

Patients with incomplete medication records

Uncooperative or cognitively impaired patients without a caregiver to provide reliable history

Sample Size:
A total of 100 elderly patients meeting the inclusion criteria were consecutively enrolled during the study period.

Data Collection Tools and Procedure:
Patient demographics, medical history, and medication profiles were recorded using a pre-designed data collection form. All participants were monitored for the development of adverse drug reactions (ADRs) during their hospital stay through daily clinical assessments, medication chart reviews, and laboratory investigations as needed.

Suspected ADRs were documented and evaluated using the following standardized tools:

Causality assessment: WHO-UMC criteria

Severity assessment: Modified Hartwig and Siegel Scale

Preventability assessment: Schumock and Thornton criteria

Statistical Analysis:
Descriptive statistics were used to summarize patient characteristics and ADRs. Categorical variables were expressed as frequencies and percentages. Data analysis was performed using Microsoft Excel and SPSS (Statistical Package for the Social Sciences) version 25.

Necessary permissions were obtained before starting the study. Informed consent was obtained from all participants or their legal guardians.

A total of 100 elderly patients (≥60 years) receiving polypharmacy were enrolled in this prospective observational study. The mean age of the study population was 68.2 ± 6.7 years, with a slight male predominance (54%) (Table 1).

Table 1: Demographic Profile of Study Participants (N = 100)

Incidence and Pattern of Adverse Drug Reactions (ADRs)

Among the study participants, 42 patients (42%) experienced at least one ADR during the study period. A total of 58 ADRs were documented, indicating that some individuals experienced multiple reactions (Table 2).

Table 2: Incidence of Adverse Drug Reactions (ADRs)

The majority of ADRs affected the gastrointestinal system (31.0%), followed by the central nervous system (22.4%), and skin/subcutaneous tissue (15.5%). Other organ systems involved included cardiovascular (12.1%) and renal systems (8.6%) (Table 3).

Table 3: System-wise Distribution of ADRs (N = 58 ADRs)

Figure No:1 System wise Distribution of ADRs

Drugs Implicated in ADRs

The most commonly implicated drug classes were antihypertensives (24.1%), NSAIDs (19.0%), and antidiabetic medications (17.2%). Antibiotics (13.8%) and psychotropic agents (12.1%) were also significant contributors (Table 4).

Table 4: Drug Classes Implicated in ADRs (N = 58 ADRs)

Figure No:2.Drug Classes Implicated in ADRs

Severity, Causality, and Preventability

Based on the Modified Hartwig and Siegel Scale, the majority of ADRs were of moderate severity (50.0%), followed by mild (39.7%) and severe (10.3%) reactions (Table 5).

Table 5: Severity of ADRs (Modified Hartwig and Siegel Scale)

Causality assessment using WHO-UMC criteria revealed that 46.6% of ADRs were probable, 43.1% were possible, and 10.3% were assessed as certain (Table 6).

Table 6: Causality Assessment (WHO-UMC Criteria)

Figure No:3. Causality Assessment (WHO-UMC Criteria)

Preventability analysis showed that 36.2% of ADRs were probably preventable and 19.0% were definitely preventable, whereas 44.8% were not preventable (Table 7).

Table 7: Preventability Assessment (Schumock and Thornton Criteria)

Polypharmacy Characteristics

The average number of drugs prescribed per patient was 7.8 ± 2.1. Most patients (72%) were on 5–9 medications, while 28% were exposed to ≥10 drugs, a category considered excessive polypharmacy. ADRs were more frequent among those receiving ≥10 medications (Table 8).

Table 8: Polypharmacy Profile

This prospective observational study was undertaken to assess the incidence, pattern, severity, causality, and preventability of adverse drug reactions (ADRs) in elderly patients undergoing polypharmacy. Among the 100 patients enrolled, 42% experienced at least one ADR, a figure that aligns with prior research reporting ADR rates between 30% and 50% in older adults exposed to multiple medications [8, 10, 11]. This high prevalence supports the growing consensus that elderly populations are particularly vulnerable to drug-related complications, thereby necessitating enhanced pharmacovigilance in geriatric care.

The gastrointestinal system emerged as the most commonly affected organ system (31.0%), followed by the central nervous system (22.4%) and skin (15.5%). These patterns are consistent with findings from previous literature, which also reported high incidences of gastrointestinal and neurological ADRs due to altered gastrointestinal motility and blood-brain barrier permeability associated with aging [10, 13]. Harugeri et al. [13] similarly reported gastrointestinal complications as a leading manifestation of ADRs in elderly patients.

Regarding implicated drug classes, antihypertensives (24.1%), NSAIDs (19.0%), and antidiabetic agents (17.2%) were the most frequently associated with ADRs in this study. These findings reflect commonly prescribed medications in elderly populations with chronic comorbidities such as hypertension, osteoarthritis, and diabetes [8, 12]. Moreover, Veehof et al. [11] and Rodrigues & Oliveira [12] observed similar drug class associations, underscoring the need for individualized medication management.

Severity assessment revealed that 50% of ADRs were moderate, and 10.3% were severe, posing potential risks for hospitalization and increased morbidity if unrecognized. This is consistent with the narrative review by Zazzara et al. [10], which highlighted that moderate to severe ADRs contribute significantly to clinical deterioration in older adults. Causality assessments using WHO-UMC criteria found that 46.6% of ADRs were probable and 43.1% possible, confirming a strong likelihood of association with the administered drugs—echoing patterns described in prior epidemiological studies [9, 10].

Notably, 55.2% of ADRs in this study were deemed preventable. Similar conclusions were drawn in studies such as that by Ramasubbu et al. [9], which linked polypharmacy with increased risk of preventable drug-drug interactions during cancer treatment in older patients. These observations highlight the urgent need for routine medication reviews, deprescribing protocols, and improved awareness among prescribers to mitigate preventable ADRs.

Furthermore, the study found that patients receiving ≥10 medications had a substantially higher risk of ADRs. This supports earlier work by Morin et al. [8], who demonstrated a dose-response relationship between the number of medications and ADR occurrence in older adults. Excessive polypharmacy increases the complexity of pharmacological regimens, thereby raising the likelihood of drug-drug interactions, non-adherence, and iatrogenic harm [12].

This study highlights a high incidence (42%) of adverse drug reactions (ADRs) among elderly patients receiving polypharmacy, with gastrointestinal and central nervous systems being the most commonly affected. Antihypertensives, NSAIDs, and antidiabetic medications were frequently implicated. A significant proportion of ADRs were moderate in severity and preventable, indicating opportunities for improving medication safety. Excessive polypharmacy (≥10 drugs) was associated with a higher risk of ADRs. These findings underscore the need for regular medication reviews, individualized therapy, and enhanced pharmacovigilance in geriatric care. Strengthening multidisciplinary collaboration, including clinical pharmacists and geriatric specialists, can significantly reduce ADRs and enhance therapeutic outcomes in elderly patients.

1. Bojuwoye AO, Suleman F, Perumal-Pillay VA. Polypharmacy and the occurrence of potential drug-drug interactions among geriatric patients at the outpatient pharmacy department of a regional hospital in Durban, South Africa. J Pharm Policy Pract. 2022 Jan 4;15(1):1. doi: 10.1186/s40545-021-00401-z. PMID: 34983680; PMCID: PMC8729144.
2. Routledge PA, O'Mahony MS, Woodhouse KW. Adverse drug reactions in elderly patients. Br J Clin Pharmacol. 2004 Feb;57(2):121-6. doi: 10.1046/j.1365-2125.2003.01875.x. PMID: 14748810; PMCID: PMC1884428.
3. Rakesh KB, Chowta MN, Shenoy AK, Shastry R, Pai SB. Evaluation of polypharmacy and appropriateness of prescription in geriatric patients: A cross-sectional study at a tertiary care hospital. Indian J Pharmacol. 2017 Jan-Feb;49(1):16-20. doi: 10.4103/0253-7613.201036. PMID: 28458417; PMCID: PMC5351231.
4. Runganga M, Peel NM, Hubbard RE. Multiple medication use in older patients in post-acute transitional care: a prospective cohort study. Clin Interv Aging. 2014 Sep 2;9:1453-62. doi: 10.2147/CIA.S64105. PMID: 25214773; PMCID: PMC4158998.
5. Cahir C, Curran C, Walsh C, Hickey A, Brannigan R, Kirke C, et al. Adverse drug reactions in an ageing PopulaTion (ADAPT) study: Prevalence and risk factors associated with adverse drug reaction-related hospital admissions in older patients. Front Pharmacol. 2023 Jan 13;13:1029067. doi: 10.3389/fphar.2022.1029067. PMID: 36712658; PMCID: PMC9880441.
6. Amin S, Shah S, Desai M, Shah A, Maheriya KM. An analysis of adverse drug reactions in extremes of age group at tertiary care teaching hospital. Perspect Clin Res. 2018 Apr-Jun;9(2):70-75. doi: 10.4103/picr.PICR_64_17. PMID: 29862199; PMCID: PMC5950613.
7. Yadesa TM, Kitutu FE, Tamukong R, Alele PE. Predictors of hospital-acquired adverse drug reactions: a cohort of Ugandan older adults. BMC Geriatr. 2022 Apr 23;22(1):359. doi: 10.1186/s12877-022-03003-9. PMID: 35461224; PMCID: PMC9033930.
8. Morin L, Johnell K, Laroche ML, Fastbom J, Wastesson JW. The epidemiology of polypharmacy in older adults: register-based prospective cohort study. Clin Epidemiol. 2018 Mar 12;10:289-298. doi: 10.2147/CLEP.S153458. PMID: 29559811; PMCID: PMC5856059.
9. Ramasubbu SK, Mahato SK, Agnihotri A, Pasricha RK, Nath UK, Das B Dr. Prevalence, severity, and nature of risk factors associated with drug-drug interactions in geriatric patients receiving cancer chemotherapy: A prospective study in a tertiary care teaching hospital. Cancer Treat Res Commun. 2021;26:100277. doi: 10.1016/j.ctarc.2020.100277. Epub 2020 Dec 11. PMID: 33348276.
10. Zazzara MB, Palmer K, Vetrano DL, Carfì A, Onder G. Adverse drug reactions in older adults: a narrative review of the literature. Eur Geriatr Med. 2021 Jun;12(3):463-473. doi: 10.1007/s41999-021-00481-9. Epub 2021 Mar 18. Erratum in: Eur Geriatr Med. 2022 Feb;13(1):307. doi: 10.1007/s41999-021-00591-4. PMID: 33738772; PMCID: PMC8149349.
11. Veehof LJ, Stewart RE, Meyboom-de Jong B, Haaijer-Ruskamp FM. Adverse drug reactions and polypharmacy in the elderly in general practice. Eur J Clin Pharmacol. 1999 Sep;55(7):533-6. doi: 10.1007/s002280050669. PMID: 10501824.
12. Rodrigues MC, Oliveira Cd. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review. Rev Lat Am Enfermagem. 2016 Sep 1;24:e2800. doi: 10.1590/1518-8345.1316.2800. PMID: 27598380; PMCID: PMC5016009.
13. Harugeri A, Joseph J, Parthasarathi G, Ramesh M, Guido S. Potentially inappropriate medication use in elderly patients: a study of prevalence and predictors in two teaching hospitals. J Postgrad Med. 2010 Jul-Sep;56(3):186-91. doi: 10.4103/0022-3859.68642. PMID: 20739763.