Causality assessment, severity and preventability of adverse drug reactions due to first-line antitubercular agents

Gunjan Upadhyay, Apexa B Shukla, Darshan J Dave


TB (Tuberculosis) is a common infectious disease affecting humans since very long time. Multidrug therapy with its associated adverse drug reactions is one of the major concerns for the management of TB. The current study has been conducted for identifying causality assessment, severity as well as preventability of first-line anti-tubercular agents. All the diagnosed patients of tuberculosis attending TB and chest department of tertiary care hospital of western India and received Anti-TB drugs over 6 months enrolled in the study. Demographic details, suspected drugs/groups, causality assessment, severity assessment, and preventability assessment were analyzed from reported suspected ADR (adverse drug reaction) forms. Throughout the research period of 6 months, 500 patients received Anti-TB drugs. Among them, (10%) 50 patients developed 121 adverse drug reactions. According to the WHO causality scale, 66 (54.54%) ADRs were classified as ‘probable’ and 53 (43.8%) ADR were ‘possible’. More than half of the reactions (31, 62%) were mild on the severity scale while most of the ADRs were definitely (34, 68%) preventable as per the preventability scale. Gastrointestinal system is the most common affected system (54, 47.62%) followed by dermatological disorders (26, 23.01%) and Liver and biliary system (20, 16.52%). Isoniazid (46, 38%) and Rifampicin (40, 33%) were the common cause of first-line antitubercular agents for ADRs. ADRs to antitubercular agents are a major concern for patient compliance. Patient education, intensive reporting, and management can be helpful to improve the outcome of antitubercular therapy. 


Tuberculosis; adverse drug reactions; anti tubercular drug

Full Text:



Agbabiaka, T. B., Savović, J., & Ernst, E. (2008). Methods for causality assessment of adverse drug reactions. Drug Safety, 31(1), 21-37.

Ali, M.K. , Karanja, S. , Karama, M. (2017). Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia. Pan Africam Medical Journal,, 28,197.

Alomar, M. J. (2014). Factors affecting the development of adverse drug reactions (Review article). Saudi Pharmaceutical Journal, 22(2), 83-94.

Anand, A., Seth, A., Paul, M., & Puri, P. (2006). Risk factors of Hepatotoxicity during anti-tuberculosis treatment. Medical Journal Armed Forces India, 62(1), 45-49.

Farazi, A., Sofian, M., Jabbariasl, M., & Keshavarz, S. (2014). Adverse reactions to Antituberculosis drugs in Iranian tuberculosis patients. Tuberculosis Research and Treatment, 2014, 1-6.

Francoise, B. E., Thérese, A. M., Jacques, Z. J., Ubald, O. M., Philippe, A. A., Bouba, I., Mabouang VR, S., & Emmanue, A. Z. (2019). Tuberculosis in the elderly: Epidemiology and outcomes at JAMOT Hospital of Yaounde. The Journal of Medical Research, 5(2), 65-68.

Gupta, A., Kumar, V., Natarajan, S., & Singla, R. (2020). Adverse drug reactions & drug interactions in MDR-TB patients. Indian Journal of Tuberculosis, 67(4), S69-S78.

Hartwig, S. C., Siegel, J., & Schneider, P. J. (1992). Preventability and severity assessment in reporting adverse drug reactions. American Journal of Health-System Pharmacy, 49(9), 2229-2232.

Imam, F., Sharma, M., Khayyam, K. U., Al-Harbi, N. O., Rashid, M. K., Ali, M. D., Ahmad, A., & Qamar, W. (2020). Adverse drug reaction prevalence and mechanisms of action of first-line anti-tubercular drugs. Saudi Pharmaceutical Journal, 28(3), 316-324.

Javadi, M. R., Shalviri, G., Gholami, K., Salamzadeh, J., Maghooli, G., & Mirsaeedi, S. M. (2007). Adverse reactions of anti tuberculosis drugs in hospitalized patients: Incidence, severity and risk factors. Pharmacoepidemiology and Drug Safety, 16(10), 1104-1110.

Lv, X., Tang, S., Xia, Y., Wang, X., Yuan, Y., Hu, D., Liu, F., Wu, S., Zhang, Y., Yang, Z., Tu, D., Chen, Y., Deng, P., Ma, Y., Chen, R., & Zhan, S. (2013). Adverse reactions due to directly observed treatment strategy therapy in Chinese tuberculosis patients: A prospective study. PLoS ONE, 8(6), e65037.

Maciel, E. L., Guidoni, L. M., Favero, J. L., Hadad, D. J., Molino, L. P., Jonhson, J. L., & Dietze, R. (2010). Adverse effects of the new tuberculosis treatment regimen recommended by the Brazilian National Ministry of Health. Journal Brasileiro de Pneumologia, 36(2), 232-238.

Medra org. (2020). Introductory Guide MedDRA Version 23.0 March 2020. WHO | World Health Organization.

Meng Fei, C., Zainal, H., & Hyder Ali, I. A. (2018). Evaluation of adverse reactions induced by anti-tuberculosis drugs in hospital pulau Pinang. Malaysian Journal of Medical Sciences, 25(5), 103-114.

Nahid, P., Dorman, S. E., Alipanah, N., Barry, P. M., Brozek, J. L., Cattamanchi, A., Chaisson, L. H., Chaisson, R. E., Daley, C. L., Grzemska, M., Higashi, J. M., Ho, C. S., Hopewell, P. C., Keshavjee, S. A., Lienhardt, C., Menzies, R., Merrifield, C., Narita, M., O'Brien, R., … Vernon, A. (2016). Official American Thoracic Society/Centers for disease control and prevention/Infectious Diseases Society of America clinical practice guidelines: Treatment of drug-susceptible tuberculosis. Clinical Infectious Diseases, 63(7), e147-e195.

Ohkawa, K., Hashiguchi, M., Ohno, K., Kiuchi, C., Takahashi, S., Kondo, S., Echizen, H., & Ogata, H. (2002). Risk factors for antituberculous chemotherapy induced hepatotoxicity in Japanese pediatric patients. Clinical Pharmacology & Therapeutics, 72(2), 220-226.

Rademaker, M. (2001). Do women have more adverse drug reactions? American Journal of Clinical Dermatology, 2(6), 349-351.

Saqib, A., Sarwar, M. R., Sarfraz, M., & Iftikhar, S. (2018). Causality and preventability assessment of adverse drug events of antibiotics among inpatients having different lengths of hospital stay: A multicenter, cross-sectional study in Lahore, Pakistan. BMC Pharmacology and Toxicology, 19(1).

Schumock, G.T., Thornton, J.P. (1992) Focusing on the preventability of adverse drug reactions. Hospital Pharmacy, 27(6),538.

Sevilla-Sanchez, D., Molist-Brunet, N., Amblà s-Novellas, J., Roura-Poch, P., Espaulella-Panicot, J., & Codina-Jané, C. (2016). Adverse drug events in patients with advanced chronic conditions who have a prognosis of limited life expectancy at hospital admission. European Journal of Clinical Pharmacology, 73(1), 79-89.

Sriram, S., Senthilvel, N., (2013). Detection, Monitoring and Assessment of Adverse Drug Reactions at a Private Corporate Hospital. International Journal of Science and Research, 4,851-5.

Sharma, S. K., Balamurugan, A., Saha, P. K., Pandey, R. M., & Mehra, N. K. (2002). Evaluation of clinical and Immunogenetic risk factors for the development of Hepatotoxicity during Antituberculosis treatment. American Journal of Respiratory and Critical Care Medicine, 166(7), 916-919.

Sundaran, S., Udayan, A., Hareendranath, K., Eliyas, B., Ganesan, B., Hassan, A., Subash, R., Palakkal, V., & Salahudeen, M. (2018). Study on the classification, causality, preventability and severity of adverse drug reaction using spontaneous reporting system in hospitalized patients. Pharmacy, 6(4), 108.

Talpur, B., Laghari, M., Syed Sulaiman, S., Khan, A., & Bhatti, Z. (2020). Adverse drug reactions of anti-tuberculosis treatment among children with tuberculosis. International Journal of Mycobacteriology, 9(3), 281.

WHO. (2019). Global Tuberculosis Report 2019. Geneva: World Health Organization; 2019.

WHO. (2013). 12. The use of the WHO-UMC system for standardized case causality assessment. UMC | Uppsala Monitoring Centre.

Wondwossen Abera, Waqtola Cheneke, & Gemeda Abebe. (2016). Incidence of antituberculosis-drug-induced hepatotoxicity and associated risk factors among tuberculosis patients in Dawro zone, south Ethiopia: A cohort study. International Journal of Mycobacteriology, 5(1), 14-20.

Yang, M., Pan, H., Lu, L., He, X., Chen, H., Tao, B., Liu, W., Yi, H., & Tang, S. (2019). Home-based anti-tuberculosis treatment adverse reactions (HATTAR) study: A protocol for a prospective observational study. BMJ Open, 9(3), e027321.



  • There are currently no refbacks.

Copyright (c) 2022 Dr. Gunjan Upadhyay, Dr. Apexa B Shukla, Darshan J Dave

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

ISSN Print: 2088-4559 | ISSN Online: 2477-0256
Office: Faculty of  Pharmacy, Universitas Ahmad Dahlan
Jl. Prof. Dr. Soepomo, S.H., Janturan, Warungboto, Umbulharjo, Yogyakarta, Indonesia
Kode pos 55164