Table of Contents    
ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  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


Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Date of Web Publication14-Jan-2020

Correspondence Address:
Vivian Soetikno
Salemba Raya No. 6, Jakarta 10430
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnsbm.JNSBM_31_19

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   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 Jan 23];10, Suppl S1:29-33. Available from: http://www.jnsbm.org/text.asp?2019/10/3/29/275581




   Introduction Top


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.[1],[2],[3] In 2016, the rate of TB incidence in Indonesia was approximately 39/100,000 people, with a death rate of 42/100,000 people.[1] Anti-TB drugs have been associated with adverse drug reactions (ADRs), which are classified as either minor or major.[2],[3] These ADRs can cause patients to stop using drugs, which can lead to drug resistance and therapeutic failure.[4] Minor ADRs are more common than severe ADRs,[5] and several studies have confirmed that there is a significant relationship between ADRs and TB treatment dropouts.[3],[4],[6],[7],[8],[9] Hence, in this study, we assessed the associations between ADRs and the rate of TB treatment dropout among our patients cohorts.


   Materials and Methods Top


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 Top


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].
Table 1: Characteristics of the patients included in this study

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Table 2: Adverse drug reactions of the study participants

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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 Top


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.[1] In worldwide, comparison rates between male and female TB patients are 1.9:1.[10] 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,[1],[10],[11],[12] making patient in productive age more susceptible to TB infections.[12],[13],[14],[15],[16] 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),[17] 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.[3] 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.[18] These symptoms can be overcome by using anti-TB drugs 2 h after eating or while sleeping and by taking ranitidine, metoclopramide, or omeprazole.[18],[19],[20] A significant relationship between drop out of treatment and age of patients was observed, which is consistent with similar previous study.[21] 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.[7],[21],[22] We conclude that TB patients with major ADRs are at a higher risk of dropping out of treatment (90%).

Acknowledgments

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 Top

1.
World Health Organization. Global Tuberculosis Report 2017. Geneva: World Health Organization; 2016.  Back to cited text no. 1
    
2.
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.  Back to cited text no. 2
    
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Awofeso N. Anti-tuberculosis medication side-effects constitute major factor for poor adherence to tuberculosis treatment. Bull World Health Organ 2011;86:B-D.  Back to cited text no. 3
    
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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.  Back to cited text no. 7
    
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Reni R, Wahyono TY, Yulismar Y. The occurrence of anti-tuberculosis side effects in tuberculosis patients. J Respir Indo 2016;36:222-30.  Back to cited text no. 8
    
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World Health Organization. Global Tuberculosis Report 2016. Geneva: World Health Organization; 2016.  Back to cited text no. 11
    
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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.  Back to cited text no. 12
    
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Public Health England. Tuberculosis in England 2017 Report (Presenting data to end of 2016). Public Health England; 2017.  Back to cited text no. 13
    
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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.  Back to cited text no. 14
    
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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.  Back to cited text no. 15
    
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Data Information Centre. Occupational Health Situation. Jakarta: Ministry of Health Republic of Indonesia; 2015. p. 1-8.  Back to cited text no. 16
    
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Restrepo BI. Diabetes and tuberculosis. Microbiol Spectr 2016;4:1-19.  Back to cited text no. 17
    
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Kenward H, Pelligand L, Savary-Bataille K, Elliott J. Nausea: Current knowledge of mechanisms, measurement and clinical impact. Vet J 2015;203:36-43.  Back to cited text no. 18
    
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Ton Q. Management of Common Side Effects of INH (Isonizaid), RIF (Rifampin), PZA (Pyrazinamide), and EMB (Ethambutol). Univ South Nevada; 2008. p. 6.  Back to cited text no. 19
    
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Ashkin D. Management of TB treatment complication and adverse effects problems in treatment. Am J Respir Crit Care Med 2006;174:935.  Back to cited text no. 20
    
21.
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.  Back to cited text no. 21
    
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Mahmudah U, Cahyati WH, Wahyuningsih AS. Studi kualitatif faktor yang melatar belakangi drop out pengobatan tuberculosis paru. J Kesehat Masy 2011;7:83-90.  Back to cited text no. 22
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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