Safety and acceptability of a 4-drug fixed-dose combination regimen compared with separate drugs for treatment of pulmonary tuberculosis

ABSTRACT Objective: To estimate the rates of recurrence, cure, and treatment abandonment in patients with pulmonary tuberculosis treated with a four-drug fixed-dose combination (FDC) regimen, as well as to evaluate possible associated factors. Methods: This was a retrospective observational study involving 208 patients with a confirmed diagnosis of pulmonary tuberculosis enrolled in the Hospital Tuberculosis Control Program at the Institute for Thoracic Diseases, located in the city of Rio de Janeiro, Brazil. Between January of 2007 and October of 2010, the patients were treated with the rifampin-isoniazid-pyrazinamide (RHZ) regimen, whereas, between November of 2010 and June of 2013, the patients were treated with the rifampin-isoniazid-pyrazinamide-ethambutol FDC (RHZE/FDC) regimen. Data regarding tuberculosis recurrence and mortality in the patients studied were retrieved from the Brazilian Case Registry Database and the Brazilian Mortality Database, respectively. The follow-up period comprised two years after treatment completion. Results: The rates of cure, treatment abandonment, and death were 90.4%, 4.8%, and 4.8%, respectively. There were 7 cases of recurrence during the follow-up period. No significant differences in the recurrence rate were found between the RHZ and RHZE/FDC regimen groups (p = 0.13). We identified no factors associated with the occurrence of recurrence; nor were there any statistically significant differences between the treatment groups regarding adverse effects or rates of cure, treatment abandonment, or death. Conclusions: The adoption of the RHZE/FDC regimen produced no statistically significant differences in the rates of recurrence, cure, or treatment abandonment; nor did it have any effect on the occurrence of adverse effects, in comparison with the use of the RHZ regimen.

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Inadequate Therapeutic Response to a Recommended Antituberculosis Fixed-Dose Combination Regimen in an Overweight Patient with Mycobacterium bovis Infection

Annals of Pharmacotherapy ◽

10.1345/aph.1r452 ◽

2013 ◽

Vol 47 (1) ◽

pp. e4-e4

Author(s):

Célia Lloret-Linares ◽

Stéphane Mouly ◽

Dan-Tranh Hoang-Nguyen ◽

John Evans ◽

Laurent Raskine ◽

...

Keyword(s):

Mycobacterium Bovis ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Therapeutic Drug ◽

Combination Regimen ◽

Overweight Patient ◽

Tuberculosis Complex ◽

Drug Concentrations ◽

Dose Combination ◽

Lymph Node Tuberculosis

OBJECTIVE To report a case of an overweight man with lymph node tuberculosis due to Mycobacterium bovis, a part of the Mycobacterium tuberculosis complex, treated with fixed-dose combination (FDC) chemotherapy. CASE REPORT Following guidelines, according to the patient's weight (92 kg), we prescribed the maximum recommended doses of isoniazid-rifampin-pyrazinamide FDC. It led initially to underdosing, with a poor clinical outcome, justifying increased doses and a complex regimen using separate drugs (isoniazid 600 mg, rifampin 1200 mg, and levofloxacin 1000 mg) to achieve therapeutic drug concentrations and clinical response. DISCUSSION Usually recommended doses of FDC chemotherapies may be inappropriate in overweight patients. We discuss here the different factors that may be involved in poor clinical outcomes, particularly the consequences of excess weight on drug metabolism: drug-drug interaction, FDC use, generic formulation use, intestinal malabsorption, and acetylation profile. CONCLUSIONS Therapeutic drug monitoring in overweight patients may be useful in the clinical setting to help clinicians individualize drug therapeutic regimens and optimize drug response, adherence, and safety.

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KADAR SERUM GLUTAMIC OXALOACETAT TRANSAMINASE DAN SERUM GLUTAMIC PYRUVIC TRANSAMINASE PADA PASIEN TUBERKULOSIS PARU SELAMA DUA BULAN BERJALANNYA PEMBERIAN OBAT ANTI TUBERKULOSIS KOMBINASI DOSIS TETAP

e-CliniC ◽

10.35790/ecl.2.3.2014.6068 ◽

2014 ◽

Vol 2 (3) ◽

Author(s):

Ayu R. Pribadini Nelwan ◽

Stella Palar ◽

Julia C. M. Lombo

Keyword(s):

Pulmonary Tuberculosis ◽

Serum Levels ◽

Fixed Dose Combination ◽

World Health ◽

Fixed Dose ◽

Glutamic Pyruvic Transaminase ◽

Cross Sectional ◽

The World ◽

Dose Combination ◽

Health Organization

Abstract: Tuberculosis (TB) is still a health problem around the world. According to statistics of the World Health Organization (WHO) showed that Indonesia’s ranking were down from third to fifth in the world. However there are also challenges in the treatment of tuberculosis worldwide and in Indonesia, like treatment failure, dropping out of treatment, and inappropriate treatment. This study aimed to compare the serum levels of SGOT (AST) and SGPT (ALT) in patients with pulmonary TB during two months administration of OAT KDT. This study was a cross sectional analytic study using secondary data and blood sample from patients with pulmonary TB. The samples in this study was patients with pulmonary tuberculosis, pulmonary tuberculosis first category, pulmonary tuberculosis BTA smear (+), pulmonary tuberculosis with controlled hypertension, pulmonary tuberculosis suspected MDR, pulmonary tuberculosis with secondary infections, pulmonary tuberculosis on treatment, and pulmonary tuberculosis which dropping put of treatment. The analysis of data changes on SGOT levels before and after administration of Anti-Tuberculosis Drugs (OAT) shows that the value of zcount: 2,223 >ztable: 1,645 with a significance value of p= 0,026 < 0,05. This indicates that there is an effect of the Anti Tuberculosis Drugs (OAT) fixed-dose combination toward SGOT levels. The analysis of data changes on SGPT levels before and after administration of Anti-Tuberculosis Drugs (OAT) shows that the value of zcount: 2,045 >ztable: 1,645 with a significance value of p= 0,041 < 0,05. This indicates that there is an effect of the Anti Tuberculosis Drugs (OAT) fixed-dose combination toward SGPT levels. There are a significant correlation between serum levels of glutamic oxaloacetat transaminase and glutamic pyruvic transaminase in patients with pulmonary tuberculosis during two months administration of anti-tuberculosis medication with a fixed-dose combination and an increasing levels of SGOT and SGPT in pulmonary tuberculosis patients. Abstrak: Penyakit Tuberkulosis (TB) masih merupakan masalah kesehatan di dunia. Menurut data statistik World Health Organization (WHO) menunjukkan Indonesia turun dari peringkat tiga menjadi peringkat kelima dunia. Namun masih terdapat pula tantangan dalam pengobatan TB di dunia dan Indonesia, antara lain kegagalan pengobatan, putus pengobatan, dan pengobatan yang tidak tepat. Penelitian ini ditujukan untuk mengetahui perbandingan kadar serum SGOT dan SGPT pada pasien TB Paru selama dua bulan pemberian OAT KDT. Penelitian ini merupakan penelitian analitik cross sectional dengan menggunakan data sekunder dan pengambilan sampel darah pada pasien TB Paru. Pada penelitian ini sampel yang digunakan adalah penderita TB Paru, TB Paru kategori 1, TB paru BTA (+), TB Paru dengan Hipertensi terkontrol, TB paru suspek MDR, TB Paru dengan infeksi sekunder, TB paru on treatment, dan TB paru putus obat. Hasil analisis data perubahan kadar SGOT sebelum dan setelah diberikan Obat Anti Tuberkulosis menunjukkan bahwa nilai zhitung: 2,223 >ztabel : 1,645 dengan nilai signifikansi p= 0,026 < 0,05. Hal ini menunjukkan bahwa terdapat pengaruh pemberian Obat Anti Tuberkulosis (OAT) kombinasi dosis tetap terhadap kadar SGOT. Hasil analisis data perubahan kadar SGPT sebelum dan setelah diberikan Obat Anti Tuberkulosis menunjukkan bahwa nilai zhitung: 2,045 >ztabel : 1,645 dengan nilai signifikansi p= 0,041 < 0,05. Hal ini menunjukkan bahwa terdapat pengaruh pemberian Obat Anti Tuberkulosis (OAT) kombinasi dosis tetap terhadap kadar SGPT. Terdapat hubungan yang signifikan antara kadar serum glutamic oxaloacetic transaminase dan serum glutamic pyruvic transaminase pada pasien tuberkulosis paru selama dua bulan berjalannya pemberian obat anti tuberkulosis kombinasi dosis tetap dan terdapat peningkatan kadar SGOT dan SGPT pada pasien tuberkulosis paru.

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Baseline Characteristics of Patients and the Effect of Fixed-Dose Combination Chemotherapy on Sputum Conversion Time in Active Pulmonary Tuberculosis: A Preliminary Study in Kandy District, Sri Lanka

SAARC Journal of Tuberculosis Lung Diseases and HIV/AIDS ◽

10.3126/saarctb.v5i1.3076 ◽

2010 ◽

Vol 5 (1) ◽

pp. 1-6

Author(s):

KAS Jayawardena ◽

M Samarathunga

Keyword(s):

Sri Lanka ◽

Pulmonary Tuberculosis ◽

Conversion Rate ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Heavy Smoking ◽

Active Pulmonary Tuberculosis ◽

Sputum Conversion ◽

Dose Combination ◽

Conversion Time

Main Objective: To evaluate the effect of Fixed-Dose Combination (FDC) drugs on sputum conversion time in active tuberculosis. Method: A prospective study of 58 active pulmonary tuberculosis patients in Kandy District Sri Lanka. Results: The mean sputum conversion time was 3.836 weeks (SD 2.599) and the median was 4.00 weeks. The sputum conversion rate at the end of 8 weeks was 96.36%. Initial bacillary load indicated by sputum smear grading was highly correlated with sputum conversion time (r = 0.531 P = 0.000). Gender was associated with sputum conversion time. Women had significantly shorter sputum conversion time. (T value =2.23, P = 0.03, Df = 48). Heavy smoking was associated with delayed sputum conversion in male patients (p = 0.01). Conclusion: Use of FDC in active pulmonary tuberculosis yields high sputum conversion rate with a mean sputum conversion time of 3.4 weeks. Faster sputum conversion among women may be attributed to their stronger genetic constitution and healthy lifestyles. Heavy smoking is associated with delayed sputum conversion. Key words: FDC Drugs; sputum conversion time; pulmonary tuberculosis; Sri Lanka DOI: 10.3126/saarctb.v5i1.3076 SAARC J. Tuber. Lung Dis. HIV/AIDS 2008 Vol.5(1) 1-6

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