Effect of Fixed‐Dose Combinations Antituberculosis and Separate Formulations on Clinical Symptoms, Weight Gain, Adverse Effect and Plasma Concentration in Tuberculosis and HIV Coinfection Cases

Authors

  • Titi Sundari Department of Pulmonology, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Nina Mariana Department of Research, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Debby Intan Permatasari Department of Research, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Adria Rusli Department of Pulmonology, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Pompini Agustina Sitompul Department of Pulmonology, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Rosamarlina Rosamarlina Department of Pulmonology, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Aninda Dinar Widiantari Department of Research, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Siti Maemun Department of Research, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia
  • Vivi Lisdawati Department of Research, Sulianti Saroso Infectious Disease Hospital, Jakarta, Indonesia, Indonesia

DOI:

https://doi.org/10.36408/mhjcm.v10i2.867

Keywords:

coinfection TB-HIV, fixed dose combination, separated formulation

Abstract

BACKGROUND: Fixed Dose Combination (FDC) was aimed to simplify TB therapy and facilitate physician and patient compliance.

OBJECTIVE: We aimed to evaluate the effect of FDC antituberculosis and separate formulations (SF) on clinical symptoms, weight gain, adverse effect and plasma concentration in TB/HIV cases during the intensive phase.

METHOD: Prospective cohort study was conducted in public hospital, Jakarta. We recruited TB-HIV patients in May 2018-May 2019. Patients (over than 18 years old) diagnosed with TB-HIV who consumed either FDC or SF and had not received antiretroviral. A total of 36 subjects were included in this study, 20 subjects in FDC group and 16 subjects in SF group.

RESULT:  There was not significant different between FDC and SF groups with an improvement of clinical symptoms (P = 0.70) and weight gain (P = 1.00). Gastrointestinal syndrome was 75% in FDC group; 62.5 % in SF group. Mean (±SD) of rifampicin, isoniazid, pyrazinamide plasma concentration after 2 weeks therapy in FDC group were 5.49 mg/L (±3.40 mg/L), 1.35 mg/L (±1.20 mg/L), 19.87 mg/L (±17.00 mg/L), respectively. Mean (±SD) of rifampicin, isoniazid, pyrazinamide plasma concentration in SF group were 6.42 mg/L (±4.80mg/L), 0.87 mg/L (±0.70 mg/L), 5.03 mg/L (±7.60 mg/L), respectively.

CONCLUSION: There was not significant different between FDC and SF groups on improvement of clinical symptoms and weight gain in intensive phase of therapy, the highest of adverse effects was gastrointestinal syndrome, and all subjects had normal reference ranges of rifampicin concentrations, and isoniazid and pyrazinamide below the normal range.

Downloads

Download data is not yet available.

References

1. Al-Shaer MH, Mansour H, Elewa H, Salameh P, Iqbal F. Treatment outcomes of fixed-dose combination versus separate tablet regimens in pulmonary tuberculosis patients with or without diabetes in Qatar. BMC Infect Dis. 2017 Dec 2;17(1):118.
2. Wu JT, Chiu CT, Wei YF, Lai YF. Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment. Clinics (Sao Paulo). 2015 Jun 30;70(6):429–34.
3. Albanna AS, Smith BM, Cowan D, Menzies D. Fixed-dose combination antituberculosis therapy: a systematic review and meta-analysis. Eur Respir J. 2013 Sep 1;42(3):721–32.
4. Sitepu R, Justiaty J, Purwantyastuti P, Sari FE, Soetikno V, Amzal W, et al. Evaluasi Efektifitas dan Efek Samping Obat Antituberkulosis Kategori 1 Kombinasi Dosis Tetap dan Dosis Lepasan pada Pasien Tuberkulosis Paru . [Jakarta]: Universitas Indonesia; 2018.
5. Pramudita A, Findyartini A. Fixed-dose combination antituberculosis therapy as a risk factor for tuberculosis recurrence: an evidence-based case report. Acta Med Indones - Indones J Intern Med. 2017 Apr;49(2):175–81.
6. Burhan E, Ruesen C, Ruslami R, Ginanjar A, Mangunnegoro H, Ascobat P, et al. Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients. Antimicrob Agents Chemother. 2013 Aug;57(8):3614–9.
7. Peloquin C. Antituberculosis drugs: pharmacokinetics. In: Heifets L, editor. Drug susceptibility in the chemotherapy of mycobacte-rial infections. Boca Raton, FL: CRC Press, Inc; 1991. p. 59–88.
8. Iftikhar S, Sarwar MR. Potential Disadvantages Associated with Treatment of ActiveTuberculosis Using Fixed-Dose Combination: A Review of Literature. J Basic Clin Pharm. 2017;8(0).
9. Lai JML, Yang SL, Avoi R. Treating More with Less: Effectiveness and Event Outcomes of Antituberculosis Fixed-dose Combination Drug versus Separate-drug Formulation (Ethambutol, Isoniazid, Rifampicin and Pyrazinamide) for Pulmonary Tuberculosis Patients in Real-world Clinical Practice. J Glob Infect Dis. 2019 Jan 1;11(1):2–6.
10.Al-Shaer MH, Elewa H, Alkabab Y, Nazer LH, Heysell SK. Fixed-dose combination associated with faster time to smear conversion compared to separate tablets of anti-tuberculosis drugs in patients with poorly controlled diabetes and pulmonary tuberculosis in Qatar. BMC Infect Dis. 2018 Aug 8;18(1).
11.Apers L, Wijarajah C, Mutsvangwa J, Chigara N, Mason P, van der Stuyft P. Accuracy of routine diagnosis of pulmonary tuberculosis in an area of high HIV prevalence. Int J Tuberc Lung Dis. 2004 Aug;8(8):945–51.
12.Colebunders R, Bastian I. A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis. Int J Tuberc Lung Dis. 2000 Feb;4(2):97–107.
13.Jiang F, Yan H, Liang L, Du J, Jin S, Yang S, et al. Incidence and risk factors of anti-tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients. Liver Int. 2021 Jul 1;41(7):1565–75.
14.Swaminathan S, Padmapriyadarsini C, Narendran G. HIV-associated tuberculosis: clinical update. Clin Infect Dis. 2010 May 15;50(10):1377–86.
15.Bargaje M, Bharaswadkar S, Lohidasan S, Panda BK. Plasma drug concentrations of 4-drug fixed-dose combination regimen and its efficacy for treatment of pulmonary tuberculosis under National Tuberculosis Elimination Programme: A prospective pilot study. Indian J Tuberc. 2022 Jul 1;69(3):311–9.
16.Um SW, Lee SW, Kwon SY, Yoon HI, Park KU, Song J, et al. Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels. Int J Tuberc Lung Dis. 2007 Sep;11(9):972–8.
17.Chideya S, Winston CA, Peloquin CA, Bradford WZ, Hopewell PC, Wells CD, et al. Isoniazid, rifampin, ethambutol, and pyrazinamide pharmacokinetics and treatment outcomes among a predominantly HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009 Jun 15;48(12):1685–94.
18.Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs. 2002;62(15):2169–83.
19.Prahl JB, Johansen IS, Cohen AS, Frimodt-Møller N, Andersen ÅB. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs: a prospective observational study. J Antimicrob Chemother. 2014 Oct 1;69(10):2841–7.
20.Ky Anh N, My Tung P, Kim MJ, Phuoc Long N, Cho YS, Kim DH, et al. Quantitative Analysis of Isoniazid and Its Four Primary Metabolites in Plasma of Tuberculosis Patients Using LC-MS/MS. Molecules. 2022 Dec 6;27(23):8607.
21.Aseffa A, Chukwu JN, Vahedi M, Aguwa EN, Bedru A, Mebrahtu T, et al. Efficacy and Safety of ‘Fixed Dose’ versus ‘Loose’ Drug Regimens for Treatment of Pulmonary Tuberculosis in Two High TB-Burden African Countries: A Randomized Controlled Trial. PLoS One. 2016 Jun 20;11(6):e0157434.

Additional Files

Published

2023-07-31

How to Cite

1.
Sundari T, Mariana N, Permatasari DI, Rusli A, Sitompul PA, Rosamarlina R, Widiantari AD, Maemun S, Lisdawati V. Effect of Fixed‐Dose Combinations Antituberculosis and Separate Formulations on Clinical Symptoms, Weight Gain, Adverse Effect and Plasma Concentration in Tuberculosis and HIV Coinfection Cases. Medica Hospitalia J. Clin. Med. [Internet]. 2023 Jul. 31 [cited 2024 Dec. 22];10(2):209-16. Available from: http://medicahospitalia.rskariadi.co.id/medicahospitalia/index.php/mh/article/view/867

Issue

Vol. 10 No. 2 (2023): Med Hosp; July 2023

Section

Original Article

Citation Check

License

Copyright (c) 2023 Titi Sundari, Nina Mariana, Debby I Permatasari, Adria Rusli, Pompini A. Sitompul, Rosamarlina Rosamarlina, Aninda D. Widiantari, Siti Maemun, Vivi Lisdawati

Creative Commons License

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

Copyrights Notice
Copyrights:
Researchers publishing manuscrips at Medica Hospitalis: Journal of Clinical Medicine agree with regulations as follow:
Copyrights of each article belong to researchers, and it is likewise the patent rights
Researchers admit that Medica Hospitalia: Journal of Clinical Medicine has the right of first publication
Researchers may submit manuscripts separately, manage non exclusive distribution of published manuscripts into other versions (such as: being sent to researchers’ institutional repository, publication in the books, etc), admitting that manuscripts have been firstly published at Medica Hospitalia: Journal of Clinical Medicine
License:
Medica Hospitalia: Journal of Clinical Medicine is disseminated based on provisions of Creative Common Attribution-Share Alike 4.0 Internasional It allows individuals to duplicate and disseminate manuscripts in any formats, to alter, compose and make derivatives of manuscripts for any purpose. You are not allowed to use manuscripts for commercial purposes. You should properly acknowledge, reference links, and state that alterations have been made. You can do so in proper ways, but it does not hint that the licensors support you or your usage.