Drug is a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. The World Health Organization (WHO) defined drug as “any substance or product that is used or intended to be used to modify or explore the physiological system, or pathological state in the benefit of the recipient”.1 Drugs may be used for a limited duration, or on a regular basis for chronic disorders. Despite all the benefits of the drugs, the adverse reactions associated with them are also very common. Adverse drug reaction can be defined as “an appreciably 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”.2 These are often preventable, cause of illness, which may require discontinuing a medication or modifying the doses, initial or prolongation of hospitalization. But sometimes it results in disability or can be life threatening even cause death.
WHO established the Programme for International Drug Monitoring.3 Pharmacovigilance (abbreviated PV or PhV) is the pharmacological science deals with detection, assessment, understanding and prevention of adverse effects and promotes the safe use of drugs.4 In 2005, National Pharmacovigilance Program (NPP) was introduced by the Ministry of Health and Family Welfare further, which was revised in July 2010. This program is monitored by the Central Drugs Standard Control Organization (CDSCO), New Delhi.5, 6
In a study from South India, it was observed that 3.7% of the total hospitalized patients were suffering from ADR, among which 1.3% were fatal. 0.7% of the hospital admissions were due to ADRs.7 A study by Arulmani et al. revealed that among the collected ADR reports in the hospital, 3.4% were confirmed ADR related cases which need to be hospitalised and 3.7% ADRs even developed in the patients during the time of hospital admission.8 In India there is lack of awareness regarding reporting ADR and its monitoring and thus monitoring the drug safety is one of the major problems in India. It is very necessary to enhance the awareness regarding early detection, reporting, management and further prevention of ADR and to ensure the drug safety and quality of life. Present study was conducted to evaluate the prevalence of adverse drug reactions in a tertiary care hospital in Eastern India.
MATERIALS AND METHODS
The present study of ‘Adverse Drug Reactions’ was an observational study based on the reports collected from different departments of R.G. Kar Medical College, Kolkata, West Bengal, India. Permission/consent from the Institutional Ethics Committee was taken before the study.
The ADR reports were collected from July 2014 to June 2015 in a tertiary care hospital, i.e., for twelve months. The reports were collected solely from the physicians. The reports containing information were collected from age group ranging from 1 month old to 85 years old of either sex group. The patients with inadequate informations regarding diagnosis and prescribed drugs were excluded from the study.
The causality assessment was done based on “Naranjo’s Assessment Scale”.9 A drug reaction is classified as definite, probable and possible according to the Naranjo’s Assessment algorithm. Severity assessment was done in accordance with Hartwig and Siegel scale which classifies a drug reaction as mild moderate or severe.10
In this twelve months study (July 2014 -June 2015) in a tertiary care hospital in Kolkata, 529 prescriptions were randomly collected and analyzed, total of 2256 drugs were prescribed in these prescriptions during this time period. Average number of drugs per prescription was 4.26 [Table 1].
Evaluation of 529 prescriptions revealed 303 (57.3%) adverse drug reactions among the 287 patients and that included 144 (50.17%) females and 143 (49.83%) males. The age distribution showed 104 (36.30%) patients belonged to age group of 4 months to 40 years while 183 (63.70%) belonged to the age group of 41-80 years.
Drug utilization pattern recognizes the problems in drug use, so educational programs or other interventions should be initiated to monitor the outcomes.11 In Anatomical Therapeutic Chemical (ATC) Classification System drugs are classified into 14 groups according to the therapeutic use, chemical and pharmacological attributes and route of administration. Figure 1 showed the distribution pattern of drugs causing adverse drug reaction according to ATC classification. The anti-infective agents showed the highest percentage (63.76%) followed by drugs acting on alimentary tract & metabolism (7.32%), nervous system drugs (15.33%).
Among the anti-infectives, anti-tuberculars were the most accounted antibiotic class (60, 32.79%) followed by beta lactums (40, 21.86%), antivirals (30, 16.39%), macrolides (20, 10.93%), quinolones (12, 6.56%), aminoglyosides (n=18, 9.84%), anti-malarials (1, 0.55%) & others (2, 1.09%).
Adverse Drug reactions that have been reported here affected various organ systems, as shown in Figure 2. 50.17% ADRs were related to skin and subcutaneous (144), 21.45% affected the gastrointenstinal system (62), 10.56% (30) and 8.25% (23) addressed nervous system and general disorders respectively. Hepatobiliary disorders accounted for 4.62% (13) while 1.65% (5) were related to musculoskeletal & connective tissue disorders. Respiratory and thoracic disorders showed up to 0.99% (3), whereas both blood & lymphatic system disorders and psychiatric disorders related ADRs were found to be 0.66% (2). 0.33% (1) of ADRs were related to cardiac disorders, renal & urinary disorders and endocrine disorders.
The Causality assessment was done in accordance with the Naranjo Scale which showed 5% of Definite ADRs, Probable and Possible ADRs is 40% and 55% respectively (Figure 3).
60 (19.8%) ADRs were found to be mild, 212 (69.96%) moderate and 30 (9.90%) ADRs were severe according to the severity assessment. (Figure 4)
Pharmacovigilance is the program conducted worldwide to report various adverse reactions occurring due to drugs that are already being marketed. Present study reported adverse drug reaction cases from various departments of the tertiary care hospital for a duration of one year. During this period, 287 cases of Adverse Drug Reactions (ADR) were documented among 529 patients. Among patients, reported ADR 49.83% (143) were female whereas 50.17% (144) were male. Thus almost equal distribution of male and female patients with ADR were documented in this present study that complied with an ADR report in a tertiary care teaching hospital in South India.12 However, contradictory results were reported at a tertiary care hospital at Chhattisgarh, India that highlighted a higher prevalence of ADR among females (51.29%) as compared to males (48.7%).13 Individuals differ in their response to drug metabolism due to various factors that include differences in body mass index, genetic constitution, differences on the levels of various enzymes responsible for the drug metabolism. Majority of the ADRs (63.7%) were detected among the age group 41-80 years, as was observed in a tertiary care hospital in Gujarat (>40 years).14 Similar results were observed in the studies conducted by different groups of researchers in South India,15 Chattisgarh.13 All these studies indicated prevalence of adverse drug reactions among the geriatric population. People of the older age group usually suffer from a number of disorders, thereby increasing the risk of adverse drug reactions.16
The drug mostly associated with ADR was found to be anti-infective agents (63.07%), followed by nervous system drugs (15.33%). A study in Brazil also indicated 40.7% of the ADRs were due to anti-infective agents.17 Analogous results were also reported by Sriram et al.17 and a regional pharmacovigilance centre in Portugal.18 Both these reports suggested antibiotics were the most common drug involved in adverse reaction. A study performed with Nigerian children by Priyadarshini et al. also reported antibiotics responsible for 67% of the ADRs.19 However, it was observed that Diuretics were mostly responsible for ADR in elderly patients.20 These observations therefore pose a threat on the use of antibiotics and thus clinicians must remain aware of the ill consequences of incorporating antibiotics in the therapeutic regimen of the patients.
Present study showed skin & subcutaneous tissue disorders like urticaria, and erythematous rashes comprised of 50.17% of the ADR reports, as was observed among the patients in a tertiary care hospital in Northern Brazil.21 Study conducted in Portugal was also in accordance with the present work, where it was reported 21% of the ADRs were skin manifestations.18 Rashes and skin problems were also prevalent (37%) among the Nigerian children.19 However, Sriram et al., and Singh et al., reported contradictory results, documenting gastrointestinal problem to be 37% and 39.61 %, respectively, being most prevalent manifestation among patients with reported ADR.13,15 Present study reported 21.45% of the ADR cases were related to gastrointestinal problems.
|Drug Prescribing Indicator||Amount||Percentage (%)|
|Total number of prescriptions analyzed||529||100|
|Total number of drugs prescribed||2256||100|
|Average number of drugs per encounter*||4.26||100|
|Total no. of adverse drug reactions reported||287||54.25|
|Total no. of male patients suffering from ADRs||143||49.83|
|Total no. of female patients suffering from ADRs||144||50.17|
|Patients belonged to age group of 4 months-40 years||104||36.30|
|Patients belonged to the age group of 41-80 years||183||63.70|
The causality assessment of ADRs was done using the Naranjo scale. According to causality relationship, 55% were reported as possible correlation because information on drug withdrawal was lacking or unclear. 40% were reported as probable and 5% were reported definite causal relationship. However, no new signal was detected from the present study. These data correlated with the study of Sriram et al., Priyadharsini et al. and Jose et al.12, 15, 19 However in another study, in a tertiary care hospital in Kerala, India, 71.42% of the reactions were found to be probable, 18.36% of the cases possible, 10.2% definite and no reactions were unlikely.22 Present study documented 69.96% ADRs as moderate, 19.8% ADRs mild and 9.90 % ADRs severe in ‘Severity Assessment Scale’ which was similar to the study carried by Shamna et al. and Singh et al.13, 22
Thus it can be concluded that adverse drug reaction is a significant limitation to the success of therapeutics. In order to deal with this problem Pharmacovigilance program was initiated. It is essential to improve the quality and quantity of ADR reports and to promote surveillance programs in health care facilities. Present study depicted an overview of the different types of ADRs encountered in a tertiary care hospital. It highlighted that ADR is mostly prevalent among the elder individuals. Antibiotics were the most commonly causing ADR and mainly from skin problems. Pharmacists and other health care providers should join hands together to improve the scenario. Detection, prevention and treatment of ADR will not only improve the quality of life of the patient but will also reduce the cost. Thus, implementation of pharmacovigilance programs in the hospitals is essential to ensure safe pharmacotherapy and improve patient compliance.