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INTRODUCTION
Adverse Drug Reactions (ADRs) described as "a harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product, which predicts hazard from future administration and warrants prevention or specific treatment, or alteration of the dosage regimen, or withdrawal of the product" (Edwards and Aronson, 2000).
ADRs are significant in healthcare, accounting for 5% of all hospital admissions and affecting 10-20% of hospitalized patients. Among these patients, the total occurrence of serious ADRs is 6.7%, with fatal ADRs accounting for 0.32%. A study conducted in a tertiary care hospital in South India revealed that drug-related Adverse Drug Reactions (ADRs) accounted for 0.7% of total admissions, with 1.8% of these ADRs being fatal (Einarson, 1993; Lazarou et al., 1998; Kalaiselvan et al., 2016).
Reporting mechanisms encompass spontaneous reporting systems, enabling voluntary reporting of suspected ADRs by doctors, nurses, pharmacists and patients to regulatory agencies or drug manufacturers. Active surveillance involves systematic and proactive monitoring of patients for ADRs, often utilizing electronic health records or dedicated surveillance programs. Pharmacovigilance, a scientific discipline, focuses on detecting, assessing, understanding and preventing ADRs and other drug-related issues. Tracking and analysis involve causality assessment to evaluate the likelihood that a drug caused an ADR, signal detection to identify potential safety signals from reported ADRs and data analysis to uncover patterns, trends and correlations informing regulatory decisions or further research. Challenges like underreporting and timeliness, alongside opportunities from technology, underscore the importance of comprehensive ADR monitoring and analysis in ensuring patient safety and guiding regulatory decisions (Fossouo et al., 2023; Sahu et al., 2014).
The Pharmacovigilance Programme of India (PvPI), coordinated by the Indian Pharmacopoeia Commission, monitors drug safety and Adverse Drug Reactions (ADRs) nationwide. By collecting and analyzing ADR data, PvPI ensures safe medication use, promotes awareness, trains healthcare professionals and involves the public in enhancing drug safety measures (IPC, 2024).
Objectives
Study was conducted to monitor adverse drug reactions reported from various departments of a tertiary care hospital in Belagavi Karnataka. To analyze the Predictability, Severity and Causality assessment of ADRs as per various Scales.
MATERIALS AND METHODS
Study procedure
A prospective observational study was carried out at the ADR Monitoring Center (AMC) in a tertiary care hospital in Belagavi, North Karnataka. This center operates under the PvPI. The study spanned from January 2023 to December 2023. Permission was obtained from the PvPI chief Coordinator of the tertiary healthcare center to conduct this study. Ethical clearance was obtained from the Ethics committee (KLE/COP/EC/710/2022-23). Data pertaining to the adverse drug reactions, including seriousness, recovery status, drug details and outcomes, were evaluated and collected from the ADR reports. The collected data underwent evaluation for causality, predictability, seriousness, severity and outcome utilizing appropriate scales. Analysis was conducted employing descriptive statistics to summarize and interpret the findings.
Inclusion criteria
- ADRs from OPD and IPD departments of a Tertiary care hospital, Belagavi, Karnataka, India.
- ADRs observed across all age groups.
Exclusion criteria
- ADRs resulting from the use of blood or blood products.
- ADRs associated with alternative medicine systems such as Homeopathy, Ayurveda and Unani.
RESULTS
The demographic distribution of ADRs, as depicted in Table 1, underscores the varied susceptibility across different age groups. Adults comprise 56% of the reported ADR cases, followed closely by the elderly, constituting 24% of the total. Notably, while infants and adolescents exhibit lower incidences at 2% and 4% respectively, neonates are least affected at 0.42%. The gender distribution of ADRs shows a nearly equal representation between males and females. Specifically, males constitute 51.2% of the reported ADR cases, while females represent 48.72% of the total.
| Demographic variables | No of Patients (%) n=706 | |
|---|---|---|
| Age Group | Neonates | 3 (0.42%) |
| Infants | 15 (2%) | |
| Child | 90 (13%) | |
| Adolescent | 31 (4%) | |
| Adult | 397 (56%) | |
| Elderly | 170 (24%) | |
| Gender | Male | 362 (51.2%) |
| Female | 344 (48.72%) |
The severity assessment was conducted using modified Hartwig and Siegel Scale, indicates that the maximum of the ADRs were categorized as mild, accounting for 63% of cases. Moderate severity ADRs comprised 35% of the total, while severe ADRs were less frequent at 2% (Refer Table 2).
| Scales | Types | No. of ADRs (%) |
|---|---|---|
| Severity assessment by Hartwig and Siegel Scale | Mild | 445(63%) |
| Moderate | 244 (35%) | |
| Severe | 16(2%) | |
| Predictability as per types of ADRs. | Non-Predictable | 185 (26%) |
| Predictable | 521 (74%) | |
| Seriousness as per WHO-UMC Scale. | Serious | 269 (38.01%) |
| Non-serious | 437 (61.9%) | |
| Causality Assessment as per WHO-UMC scale. | Certain | 73 (10.3%) |
| Probable | 355 (50.2%) | |
| Possible | 275 (38.9%) | |
| Unlikely | 3 (0.004%) |
The predictability of ADRs, categorized based on the types of reactions, indicates a significant proportion of ADRs were predictable, comprising 74% of cases. Conversely, non-predictable ADRs accounted for 26% of instances. This distribution suggests that a substantial majority of ADRs can be anticipated based on known drug effects or patient characteristics, underscoring the importance of risk assessment and monitoring in clinical practice (Table 2).
According to the WHO-UMC Scale, Adverse Drug Reactions (ADRs) were categorized based on seriousness, revealing a notable proportion of serious cases at 38.01%. Conversely, non-serious ADRs constituted the majority, comprising 61.9% of the total (Table 2).
The causality assessment of ADRs based on the WHO UMC scale reveals a spectrum of causal relationships. The majority of ADRs were classified as probable, accounting for 50.2% of cases, followed by possible ADRs at 38.9%. Smaller proportions were deemed certain (10.3%), while only a negligible fraction was categorized as unlikely (0.004%) (Table 2).
The actions taken following the occurrence of Adverse Drug Reactions (ADRs) are crucial for patient safety and management. The data indicates that the most common action taken was withdrawing the drug, accounting for 52.92% of cases. In contrast, the dose of the drug remained unchanged in 29.63% of instances, while it was reduced in 7.98% of cases and increased in 0.56%. Additionally, in 9.22% of cases, no specific action was applicable. These percentages reflect the diverse approaches taken by healthcare professionals in response to ADRs, emphasizing the importance of tailored interventions based on the severity and nature of the adverse event (Table 3).
| Action Taken | ADRs |
|---|---|
| Drug Withdrawn. | 383 |
| Dose of the drug not changed. | 211 |
| Dose of the drug reduced. | 57 |
| Dose of the drug increased. | 4 |
| Not applicable. | 51 |
The outcomes of ADRs, as outlined in Table 4, demonstrate various states post-ADR occurrence. The majority of ADR cases, accounting for 333(47%) of instances, were classified as "Recovering," indicating ongoing improvement. Additionally, a significant portion, comprising 280(39.6%) of cases, were "Recovered" from the ADRs. Conversely, a smaller fraction, at 85(12%), remained "Not recovered." Furthermore, a small number of cases, 3(0.004%), resolved with sequelae, while the outcome was categorized as "Unknown" in 6(0.008%) of instances (Table 4).
| Category | No of ADRs |
|---|---|
| Recovered | 280 (39.6%) |
| Not recovered | 85 (12%) |
| Recovering | 333 (47%) |
| Resolved with sequelae | 3 (0.004%) |
| Unknown | 6 (0.008%) |
The classification of adverse drug reactions based on systemic classes provides valuable insights into the diverse physiological systems affected by medication use. Gastrointestinal disorders stand out as the most frequently reported ADR, comprising 19.87% of the total reports. Underscoring the frequent occurrence of gastrointestinal symptoms such as nausea, vomiting and diarrhea. Skin and subcutaneous tissue disorders follow closely behind, representing 14.74% of the reports, indicating a substantial incidence of dermatological reactions like rash and itching. Nervous system disorders such as giddiness and headache and general disorders/administration site conditions account for 12.56% and 10.38% respectively. Other notable System Organ Class (SOC) includes metabolism and nutrition disorders (7.82%), respiratory disorders (5.38%) and blood and lymphatic system disorders (4.74%). Collectively, this data underscores the diverse range of ADRs affecting patients and the importance of systematic monitoring and management across various systemic classes to ensure patient safety and well-being (Table 5).
| Adverse Event (SOC) | Number of reports |
|---|---|
| Gastrointestinal disorders. | 155 |
| Skin and subcutaneous tissue disorders. | 115 |
| Nervous system disorders. | 98 |
| General disorders and administration site conditions. | 81 |
| Metabolism and nutrition disorders. | 61 |
| Respiratory, thoracic and mediastinal disorders. | 42 |
| Blood and lymphatic system disorders. | 37 |
| Investigations. | 30 |
| Musculoskeletal and connective tissue disorders. | 23 |
| Vascular disorders. | 23 |
| Renal and urinary disorders. | 22 |
| Infections and infestations. | 18 |
| Eye disorders. | 12 |
| Psychiatric disorders. | 15 |
| Injury, poisoning and procedural complications. | 10 |
| Endocrine disorders. | 10 |
| Hepatobiliary disorders. | 10 |
| Cardiac disorders. | 8 |
| Immune system disorders. | 5 |
| Ear and labyrinth disorders. | 3 |
| Reproductive system and breast disorders. | 2 |
| 780 |
DISCUSSION
The analysis of ADRs in this study provides significant insights into their demographic distribution, severity, predictability, causality and the affected systemic classes. In total of 706 ADRs, around 397 ADRs were observed in adults, followed by the elderly population. This observation contrasts with previous studies that reported a higher incidence of ADRs at a young age (S P et al., 2013; Kumar et al., 2017). The gender distribution in this study showed a greater occurrence of ADRs in males (362, 51.2%), aligning with findings from a study by Jindal et al. (55.86%) (Jindal et al., 2023). However, Verma et al. (2014) reported a higher incidence in females (56%) (Verma et al., 2014).
Regarding the outcomes of ADRs, most patients showed recovery after the offending drug was withdrawn and the ADRs were treated. This is consistent with the general approach to managing ADRs, where drug withdrawal is a primary intervention.
Causality assessment by the WHO-UMC scale revealed that, 355 (50.2%) were probable and 275 (38.9%) ADRs were possible. This distribution is in contrast to a finding by Venkatsubbaiah et al., who reported 48.82% of ADRs were possible and 27.17% were probable ADRs (Meda et al., 2018). Similarly, Mahesh N. Belhekar et al. found 68.8% possible ADRs and 24% probable ADRs (Belhekar et al., 2019).
The severity assessment using the Modified Hartwig and Siegel scale indicated that 244 (35%) ADRs were moderate, 445 (63%) were mild and 16 (2%) were severe. Comparable results were shown by a study conducted by Kechi et al., with 53.81% moderate and 1.39% severe ADRs as per the Modified Hartwig and Siegel Severity Scale (Keche et al., 2021). Similar conclusions was stated in a study carried out by (Palappallil et al., (2016).
Antimicrobials were associated with the highest number of ADRs (32.29%). This finding is in line with Palappallil et al., study where antibiotics were causing ADRs in 33% of patients (Palappallil et al., 2017).
In the present study, 74% of ADRs were predictable, according to the types of ADRs. This predictability rate is supported by previous studies, which reported 96.1%, 53% and 7.4% predictable ADRs, respectively (Du et al., 2019; Rabbur et al., 2005; Raut et al., 2012). The classification of ADRs based on systemic classes showed that gastrointestinal disorders were the most common (19.87%), followed by skin and subcutaneous tissue disorders (14.74%) and nervous system disorders (12.56%). This differs from the findings of Ratan J. Lihite et al., who reported 63.52% skin-related ADRs and 15.29% nervous system-related ADRs (Lihite et al., 2017).
Routine monitoring of patients, early diagnosis and selecting the best possible drugs from different groups can significantly minimize adverse drug reactions. Patients prescribed with a narrow therapeutic index and medicines affecting vital functions should be monitored strictly to ensure safety (Badar et al., 2018).
CONCLUSION
The analysis of adverse drug reactions across various demographics provides crucial insights into the patterns and implications of these reactions, which are vital for enhancing patient safety and optimizing pharmacological interventions. The high predictability of ADRs suggests that many reactions can be anticipated and prevented through diligent risk assessment and patient monitoring. The demographic variations in ADR susceptibility underscore the necessity for personalized approaches to drug therapy. The diverse systemic classes affected by ADRs highlight the importance of holistic patient monitoring to ensure safety and well-being. Additionally, strengthening pharmacovigilance systems and promoting patient education on ADRs can contribute to early detection and timely intervention.