|Year : 2019 | Volume
| Issue : 3 | Page : 29-33
Associations between the adverse drug reactions and the tuberculosis treatment dropout rates at the Cempaka Putih Islamic Hospital in Jakarta, Indonesia
Indrianti Asril, Vivian Soetikno, Purwantyastuti Ascobat
Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
|Date of Web Publication||14-Jan-2020|
Salemba Raya No. 6, Jakarta 10430
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: Tuberculosis (TB) treatment is associated with various adverse drug reactions (ADRs). The aim of this study was to determine the associations between ADRs and the rate of TB treatment dropout among the patients at Cempaka Putih Islamic Hospital in Jakarta, Indonesia. Materials and Methods: A cross-sectional study was conducted based on the medical records of the TB patients treated at Lung Polyclinic of Cempaka Putih Islamic Hospital between January 2016 and December 2017. Results: Of 178 study participants, 80 had a history of ADR while the other 98 did not. There were statistically significant relationships between the rate of TB treatment dropout and the characteristics of patient, including the age (P = 0.022, prevalence ratio [PR] = 0.599, 95% confidence interval [CI] = 0.408–0.870) and ADR type (P = 0.001, PR = 5.333, 95% CI = 1.402–20.285). Furthermore, there were significant relationships between ADRs and comorbid disease (P = 0.000, PR = 1.871, 95% CI = 1.370–2.555). However, ADR treatment status based on the given guidelines does not have a statistically significant relationship with the rate of TB treatment dropout (P = 0.172, PR = 2.028, 95% CI = 0.582–7.071). Conclusion: The results of this study showed that age and ADR type significantly increased the prevalence of the rate of TB treatment dropout among our patient cohorts.
Keywords: Adverse drug reaction, anti-tuberculosis drugs, patient dropouts, tuberculosis
|How to cite this article:|
Asril I, Soetikno V, Ascobat P. Associations between the adverse drug reactions and the tuberculosis treatment dropout rates at the Cempaka Putih Islamic Hospital in Jakarta, Indonesia. J Nat Sc Biol Med 2019;10, Suppl S1:29-33
|How to cite this URL:|
Asril I, Soetikno V, Ascobat P. Associations between the adverse drug reactions and the tuberculosis treatment dropout rates at the Cempaka Putih Islamic Hospital in Jakarta, Indonesia. J Nat Sc Biol Med [serial online] 2019 [cited 2020 Jul 13];10, Suppl S1:29-33. Available from: http://www.jnsbm.org/text.asp?2019/10/3/29/275581
| Introduction|| |
Tuberculosis (TB) is the ninth leading cause of death worldwide, and it is the leading cause of death from a single infectious agent, ranking above the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome.,, In 2016, the rate of TB incidence in Indonesia was approximately 39/100,000 people, with a death rate of 42/100,000 people. Anti-TB drugs have been associated with adverse drug reactions (ADRs), which are classified as either minor or major., These ADRs can cause patients to stop using drugs, which can lead to drug resistance and therapeutic failure. Minor ADRs are more common than severe ADRs, and several studies have confirmed that there is a significant relationship between ADRs and TB treatment dropouts.,,,,, Hence, in this study, we assessed the associations between ADRs and the rate of TB treatment dropout among our patients cohorts.
| Materials and Methods|| |
The medical records of the TB patients admitted to Lung Polyclinic of the Cempaka Putih Islamic Hospital in Jakarta, Indonesia, between January 2016 and December 2017 were retrospectively analyzed using a cross-sectional study design. A total of 178 newly diagnosed lung TB patients were enrolled in the study after applying the inclusion and exclusion criteria. The study participants consisted of 70 patients who completed their TB treatments and 108 patients who dropped out of their treatments. The inclusion criteria were as follows: patients being treated with first-line anti-TB drugs who had readable medical records. The exclusion criteria were as follows: patients with extrapulmonary TB, TB patients that were not evaluated, pediatric patients, and patients with failed treatments.
All the statistical analyses were performed using IBM SPSS Statistics for Windows version 20.0 (IBM Corp., Armonk, NY, USA). The values were expressed using the prevalence ratio (PR) and 95% confidence interval (CI). P < 0.05 was considered to be statistically significant, and the Chi-square and Fisher's exact tests were used to analyze the data. The study was reviewed and approved by the Institutional Ethics Committee of the Faculty of Medicine at the University of Indonesia.
| Results|| |
About 50.9% of female and 49.1% of male patients dropped out of treatment. The other demographics of patients who dropped out included, productive age individuals (aged 15–64) (64.1%), high school graduates (48.1%), privately employed individuals (49.1%), and underweight individuals (based on the body mass index) (50.0%) [Table 1]. Major ADRs was the most common reason for the patients to drop out of treatment [Table 2].
A statistically significant difference between comorbid diseases and ADRs (P = 0.000, PR = 1.871, 95% CI = 1.370–2.555) was observed [Table 3]. There were statistically significant differences between the patient's age and the treatment outcome (P = 0.022, PR = 0.599, 95% CI = 0.408–0.879) [Table 4]. A statistically significant difference between the types of ADR and the results of the treatment (P = 0.001, PR = 5.333, 95% CI = 1.402–20.285) was also observed [Table 5]. More patients with major ADRs who dropped out of treatment than patients with minor ADRs.
|Table 3: Correlations between the patient characteristics and the adverse disease reactions|
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|Table 4: Correlations between the patient characteristics and the treatment results|
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|Table 5: Correlations between the adverse disease reaction types and the treatment results|
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There was no statistically significant difference between the status of ADR therapy and the results of the treatment (P = 0.073, PR = 0.403, 95% CI = 0.307–0.528) [Table 6]. Statistically significant differences were not observed between the status of ADR therapy according to the guidelines and the treatment outcome (P = 0.172, PR = 2.028, 95% CI = 0.582–7.071) [Table 7].
|Table 6: Correlations between the adverse disease reaction therapy status and the treatment results|
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|Table 7: Correlations between the adverse drug reaction therapy status according to the guidelines and the treatment results|
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| Discussion|| |
In this study, among 178 patients, there were more male patients (53.4%) than female patients (46.6%), which was consistent with WHO Global TB Report. In worldwide, comparison rates between male and female TB patients are 1.9:1. This is because smoking, which is one of the high-risk factors for TB is more common in men than women. Cigarette smoke has immunosuppressive effects on the airway's immune system,,,, making patient in productive age more susceptible to TB infections.,,,, Diabetes mellitus (DM) was also the most common comorbidities in this study. Diabetes increases the risk of TB by three folds (relative risk 3.11; 95% CI 2.27–4.26), and currently, there are more TB patients with comorbid DM than HIV.
The most common ADRs were nausea, vomiting, and decreased appetite. The World health organization reported in 2008 that dyspepsia is one of the complaints which caused 23% of patients stop treatment in the intensive phase. Nausea, vomiting, decreased appetite, and abdominal pain can occur as a result of the drugs and their metabolites that work as chemical mutagens which stimulate vagus nerve afferent and release of 5-HT which then stimulates the vomiting center at the brain stem. These symptoms can be overcome by using anti-TB drugs 2 h after eating or while sleeping and by taking ranitidine, metoclopramide, or omeprazole.,, A significant relationship between drop out of treatment and age of patients was observed, which is consistent with similar previous study. Among 178 patients, there were 80 patients who had a history of ADRs, and the type of ADRs also influenced the patient to drop out. More patients with major ADRs dropped out of treatment than patients with minor ADRs. However, the status of ADR therapy did not influence the results of the treatment because dropout was influenced by the lack of knowledge of patients about TB, lack of supervision on taking medicines, and the patients perception of being healed.,, We conclude that TB patients with major ADRs are at a higher risk of dropping out of treatment (90%).
The authors would like to thank Hibah PITTA Universitas, Indonesia.
Financial support and sponsorship
The 3rd ICE on IMERI committee supported the peer review and manuscript preparation of this article. This research was financially supported by grants from Hibah PITTA Universitas Indonesia.
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization. Global Tuberculosis Report 2017. Geneva: World Health Organization; 2016.
Subuh M, Widaningrum C, Uyainah A, Yuwono A, Nawas A, Wuryaningtyas B, et al
. National Guidelines of Tuberculosis Control. 2014 ed. Indonesia: Ministry of Health Republic of Indonesia; 2014. p. 1-37.
Awofeso N. Anti-tuberculosis medication side-effects constitute major factor for poor adherence to tuberculosis treatment. Bull World Health Organ 2011;86:B-D.
Honnaddi UC, Honnaddi MU, Tharangini SR, Hossain T, Somani R. Adverse drug reactions to first line anti-tubercular drugs a pharmacovigilance study. Int J Clin Pharmacol Res 2016;6:51-4.
Oliviera I, Kholis FN, Ngestiningsih D. The pattern of comorbid disease events and side effects of anti-tuberculosis in tuberculosis patients at Dr. Kariadi Hospital. J Kedokt Diponegoro 2016;5:1081-109.
Rian S. The Effect of Anti-tuberculosis Side Effects and the Occurence of Default at Pondok Kopi Islamic Hospital East Jakarta, Between January 2008 and May 2010. Jakarta: University of Indonesia; 2010. p. 110.
Himawan AB, Hadisaputro S, Suprihati S. Various incidence of drop out risk factors of pulmonary tuberculosis. J Publikasi Kesehatan Masyarakat Indones 2013;2:57-63.
Reni R, Wahyono TY, Yulismar Y. The occurrence of anti-tuberculosis side effects in tuberculosis patients. J Respir Indo 2016;36:222-30.
Sari ID, Yuniar Y, Syarippudin M. Monitoring of anti-tuberculosis fixed dose combinations category 1 side effects at Banten and West Java provinces. Media Litbangkes 2014;24:28-35.
Nhamoyebonde S, Leslie A. Biological differences between the sexes and susceptibility to tuberculosis. J Infect Dis 2014;209 Suppl 3:S100-6.
World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016.
Susilowati S, Yulia Y. An overview of the factors that influence anti-tuberculosis drop out in adult patients with tuberculosis. Jakarta. FIK UI 2014;7:1-7.
Public Health England. Tuberculosis in England 2017 Report (Presenting data to end of 2016). Public Health England; 2017.
Gülbay BE, Gürkan OU, Yildiz OA, Onen ZP, Erkekol FO, Baççioǧlu A, et al.
Side effects due to primary antituberculosis drugs during the initial phase of therapy in 1149 hospitalized patients for tuberculosis. Respir Med 2006;100:1834-42.
Adriztina I, Adnan A, Haryuna SH, Siagian P, Sarumpaet S. Gangguan pendengaran dan keseimbangan pada penderita Tuberkulosis yang mendapat pengobatan antituberkulosis kategori 1 dan 2 (Hearing and balance disorders in Tuberculosis patients who received antituberculosis treatment in categories 1 and 2). J Kesehat Masy 2014;8:430-6.
Data Information Centre. Occupational Health Situation. Jakarta: Ministry of Health Republic of Indonesia; 2015. p. 1-8.
Restrepo BI. Diabetes and tuberculosis. Microbiol Spectr 2016;4:1-19.
Kenward H, Pelligand L, Savary-Bataille K, Elliott J. Nausea: Current knowledge of mechanisms, measurement and clinical impact. Vet J 2015;203:36-43.
Ton Q. Management of Common Side Effects of INH (Isonizaid), RIF (Rifampin), PZA (Pyrazinamide), and EMB (Ethambutol). Univ South Nevada; 2008. p. 6.
Ashkin D. Management of TB treatment complication and adverse effects problems in treatment. Am J Respir Crit Care Med 2006;174:935.
Khamidah K, Susmaneli H. Faktor-faktor yang berhubungan dengan putus berobat pada penderita TB paru BTA positif di wilayah kerja puskesmas Harapan Jaya. J Kesehat Masy 2016;3:88-92.
Mahmudah U, Cahyati WH, Wahyuningsih AS. Studi kualitatif faktor yang melatar belakangi drop out pengobatan tuberculosis paru. J Kesehat Masy 2011;7:83-90.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]