DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20190918

An observational study to analyze predisposing factors, causality, severity and preventability of adverse drug reactions among multidrug resistant tuberculosis patients treated under RNTCP program in Northern India

Preet Lakhani, Divya Singh, Shireen Barua, Suchi Jain, Surya Kant, Ajay Verma, Amod K. Sachan, Rajendra Nath, Rakesh K. Dixit

Abstract


Background: There were 4.1% of all new cases and 19% of previously treated patients were diagnosed with either multidrug resistant or rifampicin resistant tuberculosis in 2016. In the state of Uttar Pradesh, there were 2.16 new cases and 44,531 previously treated cases. The objectives of the study were to assess the predisposing factors, causality assessment, severity grading and avoidability of the adverse drug reactions (ADRs) of the antitubercular drugs in MDR-TB patients in a tertiary care hospital of northern India.

Methods: This prospective observational study was conducted for 12 months at a tertiary care hospital. The patients with MDR tuberculosis on treatment with DOTS Plus regimen under RNTCP and who met the inclusion exclusion criteria were recruited after informed consent. ADRs were monitored daily till the patients remained admitted and thereafter monthly. Predisposing factors were recorded. Causality assessment was performed by Naranjo scale and WHO UMC scale, severity by Hartwig’s scale and avoidability by Halla’s scale.

Results: There were 115 patients were recruited, 70 developed at least one ADR. 98 ADRs were reported. The commonest ADR reported were – gastrointestinal (38.76%), neurological (21.24%) and hepatobiliary (8.16%). Diabetes and HIV predisposed to development of ADRs. 58.18% ADRs were classified as possible and 37.5% as probable by Naranjo’s scale. 51.02% ADRs were classified as probable and 42.83% as possible by WHO-UMC. 56% were classified as mild, 36% moderate, and 6% severe via Hartwig’s scale. 51 ADRs were classified as avoidable and 40 ADRs were possibly avoidable.

Conclusions: Monitoring and assessment of ADRs is necessary to promote awareness, curb resistance and maintain adherence.


Keywords


ADR assessment, MDR-TB, Naranjo’s scale, Tuberculosis, WHO-UMC scale

Full Text:

PDF

References


World Health Organization. Drug-resistant TB: Totally drug-resistant TB FAQ. Geneva: World Health Organization; 2016. Available at: http://www.who.int/tb/areas-of-work/drug-resistant-tb/totally-drug-resistant-tb-faq/en/ (Accessed 3 November 2018).

World Health Organization. Drug-resistant TB: global situation. Geneva: World Health Organization; 2016. Available at https://www.who.int/tb/areas-of-work/drug-resistant-tb/global-situation/en/ (Accessed 3 November 2018).

Guidelines for the programmatic management of drug-resistant tuberculosis- 2011 update. Geneva: World Health Organization; 2011:1-44. Available at: http://apps.who.int/iris/bitstream/handle/10665/44597/9789241501583_eng.pdf?sequence=1 (Accessed 15 November 2018).

Dela AI, Tank NKD, Singh AP, Piparva KG. Adverse drug reactions and treatment outcome analysis of DOTS-plus therapy of MDR-TB patients at district tuberculosis centre: A four year retrospective study. Lung India. 2017;34(6):522-6. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5684809/ Accessed 15 November 2018

Rathod KB, Borkar MS, Lamb AR, Suryavanshi SL, Surwade GA, Pandey VR. Adverse events among patients of multi drug resistant tuberculosis receiving second line anti TB treatment. Int J Sci Rep. 2015 Oct;1(6):253-7.

Verma R, Mahor GR, Shrivastava AK, Pathak P. Adverse drug reactions associated with first line anti-tubercular drugs in a tertiary care hospital of central India: a study of clinical presentations, causality, and severity. Asian J Pharm Clin Res. 2014;7(5):140-3.

Yang TW, Park HO, Jang HN, Yang JH, Kim SH, Moon SH, et al. Side effects associated with the treatment of multidrug-resistant tuberculosis at a tuberculosis referral hospital in South Korea: A retrospective study. Medicine (Baltimore). 2017;96(28):e7482. Available atL https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515762/ Accessed 15 November 2018

Waghmare MA, Utpat K, Joshi JM. Treatment outcomes of drug-resistant pulmonary tuberculosis under programmatic management of multidrug-resistant tuberculosis, at tertiary care center in Mumbai. Med J DY Patil Univ. 2017;10:41-5.

Kapadia VK, Tripathi SB. Adverse Drug Reactions and Outcome Analysis of MDR TB Patients on DOTS Plus Regimen. Ntl J Com-munity Med. 2015;7(1):5-9.

Jain K, Desai M, Solanki R, Dikshit RK. Treatment outcome of standardized regimen in patients with multidrug resistant tuberculosis. J Pharmacol Pharmacother. 2014;5(2):145-9. Available at: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2014;volume=5;issue=2;spage=145;epage=149;aulast=Jain Accessed 15 November 2018

Vega P, Sweetland A, Acha J. Psychiatric issues in the management of patients with multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2004;8:749-58. PMid:15182146.

Singh R, Gothi D, Joshi JM. Multidrug resistant tuberculosis: Role of previous treatment with second line therapy on treatment outcome. Lung India 2007;24:54-7. Available at: http://www.lungindia.com/article.asp?issn=0970-2113;year=2007;volume=24;issue=2;spage=54;epage=57;aulast=Singh Accessed 18 November 2018

Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int. 2011;79(1):33-45. Available at: https://www.kidney-international.org/article/S0085-2538(15)54676-0/fulltext. (Accessed 18 November 2018).

Satti H, Mafukidze A, Jooste PL, McLaughlin MM, Farmer PE, Seung KJ. High rate of hypothyroidism among patients treated for multidrug-resistant tuberculosis in Lesotho. Int J Tuberc Lung Dis. 2012;16(4):468-72. PMid:22326109.