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 Table of Contents  
Year : 2016  |  Volume : 3  |  Issue : 2  |  Page : 51-54

Adverse drug reaction monitoring through active surveillance of antitubercular therapy in an urban tertiary care center

1 Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, India
2 Department of Pharmacology, Medical College, Kolkata, West Bengal, India
3 Department of Anaesthesiology, Calcutta National Medical College, Kolkata, West Bengal, India
4 Department of Dermatology, Medical College, Kolkata, West Bengal, India

Date of Web Publication29-Jun-2016

Correspondence Address:
Dr. Manab Nandy
95 B, Bidhan Nagar Road, 18/234 Hudco Housing Estate, Kolkata - 700 054, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2225-6482.184913

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Background and Objectives: Antitubercular drugs just like other drugs used in clinical practice are not free from ADRs(Adverse drug reactions).The added problem is that combination of drugs are used for prolonged periods of time. Moreover the ADRs to drugs used is one of the major reasons for patient default, hence leading to emergence of resistant organisms. Identification of the ADR profile of drugs in a hospital setup can be useful for the prevention, early detection and management of ADRs. 1) We aim to study the demographic profile of patients receiving Antitubercular therapy. 2) To identify the pattern and incidence of ADRs in the intensive phase Antitubercular therapy following DOTS strategy. Materials and Methods: A descriptive longitudinal study conducted for twelve months at tertiary care hospital in Eastern India. All the adult T.B. patients attending the outpatient department from January 2015 till December 2015 were included as per the study criteria and were monitored for ADRs. The data were evaluated for patient demography, type of DOTS treatment, type of ADRs and Organ site/system affected. ADRs were then subjected to severity assessment as per Hartwig scale.Statistical analysis was done using statistical software Graf Pad Prism version 4.03 for Windows. Results: Out of 296 patients, majority were males (59.79%), belonged to the age group of 20-30years(53.37%). Out of 296 patients 196 patients developed 312 detected ADRS mostly reported in the 5th week of DOTS therapy. In 11(5.61%) cases drugs were withdrawn, 21(10.71%) cases drugs were reduced and remaining 164 (83.67%) cases drugs were continued in original dose. Among them 164 cases received symptomatic treatment. The most common organ system involved was G.I.T. The most common type of ADR was nausea and vomiting (23.07%). On evaluation of severity assessment showed that most of the patients ADRs were of mild level-1(79.39%). Conclusion: Regular ADR monitoring is required to reduce morbidity and development of multiple drug resistance among patients with ADRs and also to improve patient compliance.

Keywords: Adverse drug reaction, antitubercular drugs, directly observed treatment short-course therapy, tuberculosis

How to cite this article:
Naser SM, Nandy M, Banu P, Banerjee A, Paul S, Podder I, Mukherjee M. Adverse drug reaction monitoring through active surveillance of antitubercular therapy in an urban tertiary care center. Community Acquir Infect 2016;3:51-4

How to cite this URL:
Naser SM, Nandy M, Banu P, Banerjee A, Paul S, Podder I, Mukherjee M. Adverse drug reaction monitoring through active surveillance of antitubercular therapy in an urban tertiary care center. Community Acquir Infect [serial online] 2016 [cited 2023 May 29];3:51-4. Available from: http://www.caijournal.com/text.asp?2016/3/2/51/184913

  Introduction Top

Tuberculosis (TB) is a contagious and airborne infectious disease. It is a disease of poverty affecting mostly young adults in their most productive years. According to the WHO 2015 report, the vast majority of TB deaths are in the developing world including India and other Asian countries. About one-third of the world's population is infected with TB bacteria. [1]

The TB death rate has fallen by 35% since 1990, and the number of deaths is also declining. Globally, the percentage of people successfully treated reached the highest level at 86% in 2008. Since 1995, 41 million people have been successfully treated and up to 6 million lives saved through directly observed treatment short-course (DOTS) and the stop TB strategy. 5.8 million TB cases were notified through DOTS programs in 2009.

Antitubercular drugs (ATDs), just like other drugs have some adverse effects. As these drugs are used in combination for prolonged periods for the treatment of TB, adverse effect of one drug may be potentiated by the companion drugs. The adverse effects involve almost all systems in the body, namely, the gastrointestinal tract, liver, skin, nervous system, eyes, etc., Studies from different parts of world suggest that more than 5% of the patients on antitubercular treatment develop adverse drug reactions (ADRs). Some of the ADRs can be even fatal. [2],[3],[4]

However, no such data regarding prevalence is available in the present set-up. Hence, in this study, we have recorded the adverse effect profile of the commonly used ATDs through active surveillance in a hospital set up and compared it with the available data. We have also assessed the severity of the ADRs using the Hartwig et al. scale [5] for better ADR monitoring.


This study was undertaken to find out the incidence of ADR in the intensive phase of antitubercular therapy following DOTS strategy and to compare the result with standard data of this incidence.

  Materials and Methods Top

This was descriptive longitudinal study spanning between January 1 st and December 31 st , 2015. The study was carried out in the Pharmacology Department and Chest Medicine Department of a tertiary care hospital in Eastern India. The study was begun after obtaining approval from the Institutional Ethical Committee. The study included adult patients attending the chest medicine outpatient department with TB without preexisting liver disease, ophthalmopathy, or neuropathy. Patients who did not consent to participate were excluded. Patients previously exposed to ATDs, i.e., those in Category II were also excluded.

After inclusion each of the patients was monitored for 2 months for the appearance of ADRs while being administered the following ATDs: Isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E). The schedule for visits were:

  • Second visit on the 1 st week of therapy
  • Third visit on the 3 rd week of therapy
  • Fourth visit on the 5 th week of therapy
  • Fifth visit on the 7 th week of therapy.

ADRs (if any) have been identified or detected by interviewing these patients on their visits, about the appearance of certain clinical features pertaining to the ADRs. Any intervention following the appearance of ADRs was also recorded. The ADR profile and adopted intervention measures (if any) for all the study subjects have been preserved by using case sheets for future reference.

The results obtained from this study have been analyzed statistically and compared with the results obtained from other similar studies to see if there is any statistically significant deviation. Statistical analysis was done using statistical software GraphPad Prism version 4.03 for Windows (Graphpad Software Inc., San Diego, CA, USA). All the ADRs have been assessed for their severity using the Hartwig et al. scale [Table 1]. [5]
Table 1: The Hartwig et al. scale for adverse drug reactions[5]

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The Hartwig et al. scale [5] categorizes the reported ADRs into different levels as mild, moderate, or severe.

  Results Top

A total of 296 TB patients who attended the chest medicine outpatient department receive ATDs (DOTS therapy) were included in the study as per the stated inclusion and exclusion criteria. The demographic details of the patients selected for the study are given in [Table 2].
Table 2: The demographic details of the patients receiving directly observed treatment short-course (n=296)

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Of total 296 patients, 196 patients developed 312 ADRs, the incidence rate being 66.21%. Among the 312 ADRs most occurred in the age group between 20 and 30 years (53.37%). Results showed that of the 196 patients with ADRs 102 (52.04%) patients suffering from ADRs were male. The different types of ADRs detected are denoted with their incidence in [Table 3].
Table 3: List of adverse drug reactions detected as per WHO adverse drug reactions terminology and the implicated drugs (total number of adverse drug reactions=312)

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Of the total number of 312 detected ADRs 104 (33.33%) were reported in the 3 rd visit or 5 th week of DOTS therapy, followed by 94 (30.12%), 91 (29.16%), and 32 (10.25%) ADRs in the 1 st , 3 rd , and 7 th week of DOTS therapy, respectively.

Of the 196 patients who developed ADRs, in 11 cases (5.61%) the drugs were withdrawn (ATD was stopped). The dosage of the drugs was reduced in 21 cases (10.71%). In the remaining 164 cases (83.67%), drug was continued in original dose in spite of ADRs. Among them 164 cases (128 or 65.3%) received symptomatic treatment and the other 36 cases (21.95%) received no treatment.

Of the 196 patients who reported with different types of ADRs, 137 patients (69.89%) recovered without any complication before the end of the study. In the remaining 59 cases, ADR continued beyond 2 months. The different types of ADRs were assessed for their severity as per the Hartwig et al. scale. [5] In most of the cases, the ADR belonged to Level 1 235 cases (79.39%). The severity assessment of the ADRs is given in a tabular form in [Table 4].
Table 4: Evaluation of the severity of adverse drug reactions; using Hartwig et al. scale[5]

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  Discussion Top

Among the 296 TB patients who were selected for this study, after fulfilling the specific inclusion and exclusion criteria, 196 (66.21%) patients were detected with at least one adverse reaction. However, as several patients presented with multiple adverse reactions the total number of ADRs detected in the study was 312.

The high incidence of ADR affected patients in this study (66.21%) indicates that more such studies should be undertaken in this region to corroborate the results and to see whether patients residing in this area are more susceptible for developing ATD induced ADRs.

The incidence of ADRs in this study (66.21%) is almost 4 times high when compared with the result obtained by Tak et al. (17.02%) [6]],[ and almost double as compared to that found in the study carried out by Marra et al., [7] (30%). Other studies conducted by Kim et al., [8] Chhetri et al., [9] and Gholami et al. [10] showed the ADR incidence to be 52.6%, 54.75%, and 53.01%, respectively. The incidence of ADR due to ATDs in this study (66.21%) is almost similar to the result (66%) obtained by Zierski and Bek [11] The ADR incidence in this study is less when compared to the ADR incidence (80%) as detected by Koju et al. [12] These variations in results could be attributed to the varying number of study subjects in these studies.

Most of the literature say that the female gender is more prone to develop ADRs induced by ATDs. [7],[13],[14] However, in the present study, marginally higher male patients reported ADRs with ATDs (52.04%). This result is consistent with the findings of the studies conducted by Tak et al. [6] and Chhetri et al. [9] As most of the patients in this study were males (59.79%) so probably males reported more ADRs.

This study revealed that most of the ADRs were seen in patients aged 20-30. Gholami et al. [10] have shown that ages over sixty increase the risk of ADRs due to ATD. This is probably because most of the study patients belonged to a younger age group. Chhetri et al. [9] have; however, shown higher incidence of ADRs due to ATD in the young.

In this study, the system mostly affected by ADRs is the gastrointestinal system (48.38%). This is comparable to that found in the study conducted by another study. [15] In the same study, [15] the second most common system to be affected was skin (22.1%). In this study, skin related incidence of ADRs was 12.17%. Zierski and Bek [11] have shown drug withdrawal or alternation in 1.8% patients. In this study, drug was withdrawn in 5.6% patients and the dose was reduced in 10.7% patients. The drugs were continued in original dose in spite of ADRs in 83.67% patients as compared to 87.1% patients in the study conducted by Tak et al. [6]

In this study, 69.89% patients recovered from ADR without any complication before the end of 2 months from the inception of DOTS. In this study, most of the ADRs were of Level 1 or mild category 79.39% and only 3.71% needed hospital admission (Level 4b). Chhetri et al. [9] reported 93.33% of Level 1 severity while in the study conducted by Gholami et al. [10] 38.2% of the ADRs had severity Level 1.

  Conclusion Top

The strategy for TB control is a step toward achieving the TB-related Millennium development goals in terms of reducing the prevalence of TB by 50% by 2015. [16] It can be concluded that the study showed that DOTS therapy is safe, but more comprehensive monitoring of the patients undergoing antitubercular therapy is required to prevent or reduce the incidence of such adverse effects, at the initial stages.


This study had a few limitations. One of the major limitations was that only outpatient department patients were recruited. As the study was conducted entirely on OPD patients, their cooperation and compliance played a major role. Because of the lack of resources, biochemical tests could not be performed on the patients and the study is entirely based on clinical findings.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

World Health Organization. 10 Facts about Tuberculosis. Available from: http://www.who.int/features/factfiles/tuberculosis/en/. [Last updated on 2016 Mar].  Back to cited text no. 1
Ormerod LP, Horsfield N. Frequency and type of reactions to antituberculosis drugs: Observations in routine treatment. Tuber Lung Dis 1996;77:37-42.  Back to cited text no. 2
Dhingra VK, Rajpal S, Aggarwal N, Aggarwaln JK, Shadab K, Jain SK. Adverse drug reactions observed during DOTS. J Commun Dis 2004;36:251-9.  Back to cited text no. 3
Chukanov VI, Kaminskaia GO, Livchane E. Frequency and pattern of adverse reactions due to treatment of patients with pulmonary tuberculosis with antitubercular reserve drugs. Probl Tuberk Bolezn Legk 2004;(10):6-10.  Back to cited text no. 4
Hartwig SC, Siegel J, Schneider PJ. Preventability and severity assessment in reporting adverse drug reactions. Am J Hosp Pharm 1992;49:2229-32.  Back to cited text no. 5
Tak DK, Acharya LD, Gowrinath K, Rao PG, Subish P. Safety evaluation of antitubercular therapy under revised national tuberculosis programme in India. J Clin Diagn Res 2009;3:1395-401.  Back to cited text no. 6
Marra F, Marra CA, Bruchet N, Richardson K, Moadebi S, Elwood RK, et al. Adverse drug reactions associated with first-line anti-tuberculosis drug regimens. Int J Tuberc Lung Dis 2007;11:868-75.  Back to cited text no. 7
Kim SH, Lee BH, Lee KD, Park JS, Kim YS, Kim SH, et al. The prevalence of adverse drug reactions to a short course anti-tubercular regimen. Korean J Med 2007;73:496-502.  Back to cited text no. 8
Chhetri AK, Saha A, Verma SC, Palaian S, Mishra P, Shankar PR. Study of adverse drug reactions caused by first line anti-tubercular drugs used in directly observed treatment, short course (DOTS) therapy in Western Nepal, Pokhara. J Pak Med Assoc 2008;58:531-6.  Back to cited text no. 9
Gholami K, Kamali E, Hajiabdolbaghi M, Shalviri G. Evaluation of anti-tuberculosis induced adverse reactions in hospitalized patients. Pharm Pract (Granada) 2006;4:134-8.  Back to cited text no. 10
Zierski M, Bek E. Side-effects of drug regimens used in short-course chemotherapy for pulmonary tuberculosis. A controlled clinical study. Tubercle 1980;61:41-9.  Back to cited text no. 11
Koju D, Rao BS, Shrestha B, Sakya R, Makaju R. Occurrence of side effects from anti tuberculosis drugs in urban Nepalese population under DOTS treatment. Kathmandu Univ J Sci Eng Technol 2005;1:1.  Back to cited text no. 12
Yee D, Valiquette C, Pelletier M, Parisien I, Rocher I, Menzies D. Incidence of serious side effects from first-line antituberculosis drugs among patients treated for active tuberculosis. Am J Respir Crit Care Med 2003;167:1472-7.  Back to cited text no. 13
Kishore PV, Palailan S, Ojha P, Shankar PR. Pattern of adverse drug reactions experienced by tuberculosis patients in a tertiary care teaching hospital in Western Nepal. Pak J Pharm Sci 2008;21:51-6.  Back to cited text no. 14
Vieira DE, Gomes M. Adverse effects of tuberculosis treatment: Experience at an outpatient clinic of a teaching hospital in the city of São Paulo, Brazil. J Bras Pneumol 2008;34:1049-55.  Back to cited text no. 15
Anita N. India′s progress toward achieving the Millennium development goal. Indian J Community Med 2011;36:85-92. Available from: http://www.ijcm.org.in/article.asp?issn=0970-0218;year=2011;volume=36;issue=2;spage=85;epage=92;aulast=Nath. [Last accessed on 2016 Jan 12].  Back to cited text no. 16


  [Table 1], [Table 2], [Table 3], [Table 4]

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