Incidence of Adverse Drug Reactions (ADRs) and their Determinants among Sputum-Positive Pulmonary TB Patients in A Metropolitan Area, Bengaluru: A Prospective Study

Manasa  Divakar; Ananth Ram; Lalitha K

doi:10.55489/njcm.141020233057

Authors

Manasa Divakar Siddaganga Medical College and Research Institute, Tumakuru, Karnataka, India
Ananth Ram M S Ramaiah Medical College, Bengaluru, India
Lalitha K M S Ramaiah Medical College, Bengaluru, India

DOI:

https://doi.org/10.55489/njcm.141020233057

Keywords:

Tuberculosis, ADRs, FDC daily regimen, WHO-UMC scale, Hartwig’s severity assessment scale

Abstract

Background: India accounts for 2.42 million new Tuberculosis cases in 2022. Treatment adherence is major challenge, ADRs being one of the main causes of poor adherence. Early identification and addressing of ADRs can improve adherence, reducing associated morbidity and drug resistance. With introduction of daily FDC regimen in India, we intend to study incidence of ADRs and their determinants among Pulmonary TB patients who are on FDC daily regimen.

Methodology: Newly diagnosed drug-sensitive PTB patients aged 18 years and above were recruited. A pretested questionnaire was administered and patients were followed up to document ADRs. Causality and severity were assessed using the WHO-UMC scale and Hartwig’s severity assessment scale respectively.

Results: Among the study participants’, 95 (78.5%) developed any ADRs. Incidence rate was 13.2 (6.98–19.22) per 100-person month follow-up with GI symptoms being most common. Increasing age [OR=4.7(1.6–14.8)] and weight [OR=5.1(1.3–16.2)] were found to be significantly associated with ADRs. All ADRs were classified as ‘probable’ and ‘mild’ in nature according to WHO scale and Hartwig’s severity assessment scale respectively.

Conclusion: Occurrence of ADRs is common, most of them are mild, and occurring in intensive phase. Hence, early identification and appropriate counselling during intensive phase is critical.

References

World Health Organisation. Global Tuberculosis Report 2022 [Internet]. Geneva: World Health Organisation; 2022. Licence: CC BY-NC-SA 3.0 IGO. Available from: https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022

Central TB Division, Ministry of Health and Family Welfare. India TB Report 2023 [Internet]. New Delhi. 2023. Available from: https://tbcindia.gov.in/index1.php?lang=1&level=1&sublinkid=5613&lid=3658

Albanna AS, Smith BM, Cowan D, and Menzies D. Fixed-dose combination antituberculosis therapy: a systematic review and meta-analysis. [Internet]. Eur Respir J. 2013 Sep;42(3):721-32. Doi: https://doi.org/10.1183/09031936.00180612 PMid:23314904

Iftikhar S, Sarwar M R. Potential Disadvantages Associated with Treatment of Active Tuberculosis Using Fixed-Dose Combination: A Review of Literature [Internet]. J Basic Clin Pharm. 2017;8: S131-136. Available from: https://www.jbclinpharm.org/articles/potential-disadvantages-associated-with-treatment-of-active tuberculosis-using-fixeddose-combination-a-review-of-literature-3689.html

Aditama TY. Fixed Dose Combination for TB Treatment [Internet]. Med J Indones. 2003 May 1;114-9. Doi: https://doi.org/10.13181/mji.v12i2.99

Ramakrishna M, Maheshwari YN, Ramya JE, Krishnamoorthy K. Adverse drug reaction monitoring of antitubercular drugs during intensive phase at tertiary care medical college hospital: A prospective study [Internet]. Natl J Physiol Pharm Pharmacol 2020;10(11):976-980. Available from: https://www.njppp.com/fulltext/28-1594315424.pdf?1690192587

Singh A., Sayedda K., and Ahmed Q. Comparison of adverse drug reactions of antitubercular drugs in category 1 tuberculosis patients between daily and intermittent regimens and their impact on outcome. [Internet]. J Res Med Dent Sci. 2017;5(1):6. Doi: https://doi.org/10.5455/jrmds.2017512

Kuriachan S., Krishnan P., Chogtu B., and George MM. Assessment of adverse drug reactions to an antituberculosis regimen in a ter-tiary care hospital[Internet]. Int J Basic Clin Pharmacol. 2019 Sep 25;8(10):2202. Doi: https://doi.org/10.18203/2319-2003.ijbcp20194147

The Uppsala monitoring centre. The use of the WHO-UMC system for standardised case causality assessment [internet]. World Health Organization, Geneva. p. 1-3.Available from: https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf.

Petrova G, Stoimenova A, Dimitrova M, Kamusheva M, Petrova D, Georgiev O. Assessment of the expectancy, seriousness, and sever-ity of adverse drug reactions reported for chronic obstructive pulmonary disease therapy [internet]. SAGE Open Med. 2017 Dec;5:205031211769040. Doi: https://doi.org/10.1177/2050312117690404 PMid:28228952 PMCid:PMC5308439

Lienhardt C. Efficacy and Safety of a 4-Drug Fixed-Dose Combination Regimen Compared With Separate Drugs for Treatment of Pul-monary Tuberculosis: The Study Randomised Controlled Trial [internet]. JAMA. 2011 Apr 13;305(14):1415. [cited 2020 Oct 28] Doi: https://doi.org/10.1001/jama.2011.436

PMid:21486974

Anwith H, Kaushik S, Thenambigai R, Madhusudan M, Priyanka D, Deepthi N, et al. Effectiveness of daily directly observed treatment and short-course regimens among patients registered for treatment at an urban primary health centre in Bengaluru [internet]. In-dian J Community Fam Med. 2019;5(1):56. Doi: https://doi.org/10.4103/IJCFM.IJCFM_4_19

Duru CB, Uwakwe KA, Nnebue CC, Diwe KC, Merenu IA, Emerole CO, et al. Tuberculosis Treatment Outcomes and Determinants among Patients Treated in Hospitals in Imo State, Nigeria [internet]. OALib. 2016;03(06):1-17. Doi: https://doi.org/10.4236/oalib.1102754

Sant'Anna FM, Arau'jo-Pereira M, Schmaltz CAS, Arriaga MB, de Oliveira RVC, Andrade BB and Rolla VC. Adverse Drug Reactions Re-lated to Treatment of Drug-Susceptible Tuberculosis in Brazil: A Prospective Cohort Study [internet]. Front. Trop. Dis. 2022 Jan, (2)748310. doi: 10.3389/fitd.2021.748310. Doi: https://doi.org/10.3389/fitd.2021.748310

Bhangari K., Pulmonary Medicine, S. Sangolli B. A comparative assessment of the daily dosage regimen versus the intermittent treatment regimen of tuberculosis at the RNTCP centres in Chitradurga district IP [internet]. Indian J Immunol Respir Med. 2020 Jun 28;5(2):97-100. Doi: https://doi.org/10.18231/j.ijirm.2020.037

Mandal PK, Mandal A, Bhattacharyya SK. Comparing the Daily Versus the Intermittent Regimens of the Anti-Tubercular Chemother-apy in the Initial Intensive Phase in Non-HIV, Sputum-positive, Pulmonary Tuberculosis Patients [internet]. J Clin Diagn Res. 2013 Feb;7(2):292-5. doi: 10.7860/JCDR/2013/5122.2750. Available from: http://www.jcdr.net/article_fulltext.asp?issn=0973-709x&year=2013&volume=7&issue=2&page=292&issn=0973-709x&id=2750

Mate K, Mishra M, Munje R. Adverse Drug Reactions to a Daily Fixed-dose Combination Based Antituberculosis Treatment Regime in India's National Tuberculosis Elimination Programme: A Prospective Cohort Study [internet]. J Clin Diagn Res. 2022 Aug, Vol-16(8): OC14-OC19. DOI: 10.7860/JCDR/2022/57878.16719. Doi: https://doi.org/10.7860/JCDR/2022/57878.16719

Ahmad N, Javaid A, Syed Sulaiman SA, Afridi AK, Zainab, Khan AH. Occurrence, Management, and Risk Factors for Adverse Drug Reac-tions in Multidrug Resistant Tuberculosis Patients [internet]. Am J Ther. 2018 Sep/Oct;25(5):e533-e540. doi: 10.1097/MJT.0000000000000421. PMID: 26938643. Doi: https://doi.org/10.1097/MJT.0000000000000421 PMid:26938643

Prasad R, Singh A, Gupta N. Adverse Drug Reactions with First-Line and Second-Line Drugs in Treatment of Tuberculosis [internet]. Ann Natl Acad Med Sci (India):2021;57:16-35. DOI https://doi.org/ 10.1055/s-0040-1722535 ISSN 0379-038X. Doi: https://doi.org/10.1055/s-0040-1722535

Sharma RK, Verma GK, Tegta GR, Sood S, Rattan R, Gupta M. Spectrum of Cutaneous Adverse Drug Reactions to Anti-tubercular Drugs and Safe Therapy after Re-challenge - A Retrospective Study [internet]. Indian Dermatol Online J. 2020 Mar 9;11(2):177-181. doi: 10.4103/idoj.IDOJ_133_19. PMID: 32477975; PMCID: PMC7247648. Doi: https://doi.org/10.4103/idoj.IDOJ_133_19 PMid:32477975 PMCid:PMC7247648

Siribaddana A, Dissanayake K, Athukorala G, Pathirathne H, Senevirathna K, Upul BA, et al. Frequency of Adverse Effects of Fixed Dose Combinations in Tuberculosis and Their Effects on Treatment Outcome [Internet]. SAARC J Tuberc Lung Dis HIVAIDS. 2016 Oct 25;12(2):8-12. 2013 Doi: https://doi.org/10.3126/saarctb.v12i2.15949

Maqbool M, Zehravi M, Maqbool R, Ara I. Study of adverse drug reactions in pulmonary medicine department of a Tertiary care hos-pital, Srinagar, Jammu & Kashmir, India [internet]. CELLMED. 2021;11(2):8-1. Doi: https://doi.org/10.5812/ans.112364

Chung-Delgado K, Revilla-Montag A, Guillen-Bravo S, Velez-Segovia E, Soria-Montoya A, Nuñez-Garbin A, et al. Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru [internet]. 2011 Nov, PLoS ONE 6(11): e27610. Doi: https://doi.org/10.1371/journal.pone.0027610 PMid:22110689 PMCid:PMC3217998

Kiran M, Nagabushan H. Adverse Drug Reactions Monitoring in Patients on Antitubercular Treatment in Tertiary Care Hospital, Mandya [internet]. Biomed Pharmacol J 2021;14(2). Available from: https://bit.ly/3x9FOAA.

Gunjan U, Apexa BS, Darshan JD. Causality assessment, severity and preventability of adverse drug reactions due to first-line an-titubercular agents [internet]. Pharmaciana: Jurnal Kefarmasian. 2022 Jul 1;12(2):235-44. Doi: https://doi.org/10.12928/pharmaciana.v12i2.23008