European Journal of Cardiovascular Medicine

Adverse drug reactions (ADRs) are defined by the World Health Organization (WHO) as any noxious, unintended, and undesired effect of a drug occurring at doses used for prevention, diagnosis, or treatment of disease. ADRs represent a pressing challenge for global healthcare — they are among the leading causes of hospital admissions, extended hospital stays, patient morbidity, and preventable mortality. Estimates suggest that ADRs account for 5–10% of all hospital admissions in developed countries, with even higher rates anticipated in resource-limited or developing settings.

In India, the burden of ADRs is compounded by polypharmacy, widespread use of over-the-counter medications, self-medication practices, irrational drug use, and inadequate post-marketing drug surveillance infrastructure. Tertiary care hospitals, which manage complex and critically ill patients on multiple concurrent drug regimens, are especially high-risk environments for ADR occurrence. Despite this, under-reporting remains endemic — studies indicate that fewer than 10% of ADRs are formally reported through national pharmacovigilance channels.

The Pharmacovigilance Programme of India (PvPI), launched in 2010 and operationalised through the Indian Pharmacopoeia Commission (IPC), aims to establish a robust national network of Adverse Drug Reaction Monitoring Centres (AMCs). However, data from tertiary hospitals in southern India, particularly Telangana, remain limited in scope and detail. Most existing Indian ADR studies are retrospective, cross-sectional, or restricted to single departments, limiting their generalisability.

A prospective, multi-department design offers advantages in ADR detection sensitivity and enables active monitoring of patients across the continuum of care. This study was designed to prospectively identify and characterise ADRs across departments in a tertiary care teaching hospital, with comprehensive analysis of implicated drug classes, affected organ systems, causality, severity, and preventability — providing actionable data for clinical practice and institutional pharmacovigilance strategy.

2.1 Study Design and Setting This prospective, observational, cohort study was conducted at a 1,200-bed tertiary care teaching hospital, India, over 12 months (January to December 2024). Participating departments included General Medicine, Cardiology, Pulmonology, Gastroenterology, Endocrinology, Oncology, Neurology, Nephrology, Orthopaedics, and Dermatology. 2.2 Study Population and Sampling All inpatients aged 18 years and above admitted to the participating wards during the study period and receiving at least one prescription drug were eligible for inclusion. Patients were excluded if they were admitted with a primary diagnosis of drug overdose, self-poisoning, or deliberate self-harm. Patients who provided incomplete data or were transferred before evaluation were also excluded. Sample size was estimated based on a reported ADR incidence of 8–10% in comparable Indian tertiary care studies. Using a precision of ±2% and 95% confidence interval, a minimum sample of 3,500 patients was determined to be adequate; 3,842 patients were ultimately enrolled. 2.3 Data Collection Methods ADR data were collected using three complementary methods to maximise detection sensitivity: • Spontaneous reporting: Healthcare professionals (physicians, nurses, clinical pharmacists) were encouraged to voluntarily report suspected ADRs using standardised ADR reporting forms adapted from the PvPI format. • Active ward monitoring: Trained clinical pharmacists conducted prospective patient reviews every 48 hours across enrolled wards, reviewing case files, nursing notes, laboratory reports, and prescription charts for potential ADR signals. • Prescription review: Pharmacists cross-referenced current prescriptions against patient history and clinical notes to identify new clinical signs or laboratory abnormalities temporally associated with drug administration. All suspected ADRs were documented in a structured case report form capturing: patient demographics, diagnosis, all concurrent medications (name, dose, route, frequency, duration), ADR description, onset and duration, management, outcome, and prior drug history. 2.4 Assessment Tools Each documented ADR was assessed using three standardised instruments: • Naranjo Algorithm: A 10-item questionnaire generating a score that classifies causality as Definite (≥9), Probable (5–8), Possible (1–4), or Doubtful (≤0). • WHO-UMC Causality Categories: Supplementary causality classification into Certain, Probable/Likely, Possible, Unlikely, Conditional/Unclassified, and Unassessable/Unclassifiable. • Modified Hartwig and Siegel Scale: Severity graded as Mild (level 1–2), Moderate (level 3–4), or Severe (level 5–7) based on clinical impact and intervention required. • Schumock and Thornton Preventability Criteria (1992): ADRs classified as Definitely Preventable, Probably Preventable, or Not Preventable based on prescribing appropriateness, drug selection, monitoring, and documented allergy history. 2.5 Ethical Considerations The study protocol was reviewed and approved by the Institutional Ethics Committee. Written informed consent was obtained from all enrolled patients. Patient data were anonymised at source and stored in a password-protected, access-controlled database. The study was conducted in accordance with the Declaration of Helsinki (2013 revision) and Indian Council of Medical Research (ICMR) bioethical guidelines. 2.6 Statistical Analysis Data were entered into Microsoft Excel and analysed using SPSS Statistics version 26.0 (IBM Corp., USA). Descriptive statistics were used for categorical and continuous variables. Frequency distributions and proportions were calculated for all ADR characteristics. Chi-square test was applied to evaluate associations between categorical variables. A p-value <0.05 was considered statistically significant.

3.1 Patient Demographics and ADR Incidence

A total of 3,842 patients were enrolled during the study period. Of these, 312 patients experienced one or more ADRs, yielding an overall ADR incidence of 8.12%. Some patients experienced multiple ADRs (n = 27), totalling 341 individual ADR events. Table 1 summarises the baseline demographic characteristics of patients with ADRs.

Table 1: Demographic Characteristics of Patients with ADRs (n = 312)

Patients in the 51–70 year age group were most frequently affected (42.0%), likely reflecting the higher prevalence of multimorbidity and polypharmacy in this cohort. Female patients were significantly more represented (58.3% vs 41.7%; p = 0.03).

3.2 Drug Classes Implicated in ADRs

Antimicrobials were the most common drug class associated with ADRs (27.6%), followed by non-steroidal anti-inflammatory drugs (NSAIDs; 18.3%), cardiovascular drugs (15.7%), antidiabetic agents (11.2%), and proton pump inhibitors (8.7%). Table 2 presents the complete breakdown.

Table 2: Drug Classes Implicated in ADRs (n = 341 events)

3.3 Organ Systems Affected

Gastrointestinal manifestations were the most frequently observed ADR category (32.4%), including nausea, vomiting, diarrhoea, and gastrointestinal bleeding. Dermatological reactions constituted 21.7% of ADRs, primarily rash, urticaria, and pruritus. Renal and haematological systems were also significantly implicated. Table 3 details the distribution.

Table 3: Organ Systems Affected by ADRs

3.4 Causality, Severity, and Preventability Assessment

Table 4 presents the results of the three ADR assessment instruments applied in this study.

Among preventable ADRs, the most common contributing factors identified were: use of a drug with a documented prior allergy (31.2%), incorrect dose or duration (27.4%), lack of adequate therapeutic drug monitoring (21.6%), and clinically significant drug-drug interactions (19.8%).

3.5 Outcomes of ADRs

The majority of ADRs resolved completely with appropriate management (82.4%). ADR-related intervention included withdrawal of the causative drug (79.1%), dose adjustment (12.3%), and addition of antidote or treatment for the ADR (8.6%). Three patients (0.96%) experienced life-threatening events requiring ICU admission; all recovered fully. No fatalities directly attributable to ADRs were recorded during the study period.

Table 4: ADR Assessment — Causality, Severity, and Preventability

This prospective, multi-department study identified an ADR incidence of 8.12% among hospitalised patients, consistent with the 5–10% range reported in comparable Indian and international studies. The active monitoring approach employed here likely captured a greater proportion of ADRs than passive spontaneous-reporting-only methodologies, which are known to result in significant under-detection.

The female predominance in ADR occurrence (58.3%) corroborates findings from several pharmacoepidemiological studies and has been attributed to pharmacokinetic differences in drug absorption, distribution, and metabolism, as well as hormonal influences on drug transporters. The higher ADR burden in patients aged 51–70 years reflects the compounding effects of physiological organ decline with ageing, increased multimorbidity, and polypharmacy — all of which potentiate ADR risk.

Antimicrobials were the leading ADR-implicated class (27.6%), a finding consistently replicated across Indian tertiary care ADR studies. Beta-lactam antibiotics and fluoroquinolones were particularly frequent culprits. The high proportion of antibiotic-related ADRs in Indian hospitals is partly explained by the widespread use of broad-spectrum agents, often without strict microbiological indication — a pattern that also carries implications for antimicrobial stewardship.

The predominance of gastrointestinal ADRs (32.4%) reflects the systemic and local mucosal toxicity of commonly prescribed agents including NSAIDs, antibiotics, and anticoagulants. Dermatological manifestations (21.7%), predominantly cutaneous drug hypersensitivity reactions, underscore the importance of thorough allergy documentation and structured pre-prescribing allergy assessment. Two severe cases of Stevens-Johnson Syndrome (SJS) were observed, both attributable to sulfonamide antibiotics — reinforcing established hypersensitivity risk profiles.

The finding that 34.9% of ADRs were preventable is clinically significant and offers a concrete target for institutional intervention. The major contributory factors — undocumented allergy history, inappropriate dosing, absence of monitoring for high-risk drugs, and drug interactions — are all addressable through systematic pharmacovigilance infrastructure. Clinical pharmacy services, electronic prescribing systems with embedded safety alerts, and mandatory therapeutic drug monitoring protocols for nephrotoxic and hepatotoxic drugs hold particular promise for ADR prevention.

This study has several limitations. It was conducted at a single tertiary care centre, which may limit generalisability. Outpatient ADRs and those occurring post-discharge were not captured. Some ADRs may still have been missed despite active monitoring. Additionally, the reliance on clinician reporting for some ADR events may introduce reporting bias.

This prospective pharmacovigilance study demonstrates that ADRs constitute a significant and clinically important burden in the tertiary care setting, with an incidence of 8.12%. The high preventability fraction (34.9%) highlights important, addressable vulnerabilities in prescribing systems and monitoring practices. Antimicrobials, NSAIDs, and cardiovascular drugs are the drug classes most urgently requiring targeted monitoring strategies. Institutionalising proactive ADR surveillance programmes — incorporating dedicated clinical pharmacists, mandatory ADR reporting linked to the PvPI, structured allergy documentation, and electronic clinical decision support systems — is essential to improve medication safety, reduce ADR-related morbidity, and optimise patient outcomes in tertiary care hospitals across India.

1.  World Health Organization. International Drug Monitoring: The Role of National Centres. Technical Report Series No. 498. Geneva: WHO; 1972.

2.  Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279(15):1200-1205.

3.  Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. BMJ. 2004;329(7456):15-19.

4.  .

5.  Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30(2):239-245.

6.  World Health Organization-Uppsala Monitoring Centre (WHO-UMC). The Use of the WHO-UMC System for Standardised Case Causality Assessment. Uppsala: UMC; 2005.

7.  Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm. 1992;49(9):2229-2232.

8.  Schumock GT, Thornton JP. Focusing on the preventability of adverse drug reactions. Hosp Pharm. 1992;27(6):538.

9.  Arulmani R, Rajendran SD, Suresh B. Adverse drug reaction monitoring in a secondary care hospital in South India. Br J Clin Pharmacol. 2008;65(2):210-216.

10. Ramesh M, Pandit J, Parthasarathi G. Adverse drug reactions in a south Indian hospital — their severity and causality. Drug Saf. 2003;26(5):373-379.

11. Jose J, Rao PG. Pattern of adverse drug reactions notified by spontaneous reporting in an Indian tertiary care teaching hospital. Pharmacol Res. 2006;54(3):226-233.

12. Varma BS, Bhati N, Rathore SS. Adverse drug reactions in a tertiary care hospital: a prospective study. Int J Basic Clin Pharmacol. 2016;5(4):1524-1529.