Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis

Moussa, Leila; Bouazzi, Omaima El; Serragui, Samira; Tanani, Driss Soussi; Soulaymani, A.; Soulaymani, R.

doi:10.1177/2042098616667704

Cited by 15 publications

(8 citation statements)

References 30 publications

(37 reference statements)

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“…Indeed, a significant correlation would guide the clinician to prescribe a dose corresponding to the desired target concentration. This corroborates the results of a retrospective analysis performed by Moussa et al, 27 who found no correlation between isoniazid C 3 and weight dose in both patients having and patients not having adverse drug reactions ( r = 0.22 and 0.06, respectively). All these findings emphasize the usefulness of the isoniazid TDM in its dosage adjustment.…”

Section: Discussionsupporting

confidence: 92%

Isoniazid Therapeutic Drug Monitoring in Tunisian Patients With Tuberculosis

Alshaikheid

Romdhane

Fredj

et al. 2021

The Journal of Clinical Pharma

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A regular therapeutic drug monitoring (TDM) of isoniazid could be useful to predict the acetylation profile and to prescribe doses associated with optimal efficacy and safety. We aimed to assess the usefulness of isoniazid TDM in the Tunisian population, to describe the acetylation profile distribution in this population, and to investigate the influence of certain parameters on acetylation phenotype. We performed a retrospective study including Tunisian patients with tuberculosis underwent an isoniazid TDM. Isoniazid concentrations were measured 3 hours after drug intake (C3). Subsequent isoniazid doses were adjusted to maintain the C3 within the recommended target (1‐2 µg/mL). Patients were qualified as slow acetylators (SAs) or rapid acetylators (RAs) according to their acetylation index. Among the 255 patients, 58% were SAs and 42% were RAs. Of all patients, only 30.6% had a C3 value within the target range. A dose adjustment has been performed for patients with C3 outside the target range. C3 was controlled in 77 patients. It became within the target range in 39 patients (50.6%). The median recommended isoniazid weight doses for SAs and RAs were 2.1 ± 0.7 mg/kg and 4.2 ± 1.4 mg/kg, respectively. The multivariate analysis showed that body weight, C3, and C3/isoniazid dose were found to be significantly different between the 2 acetylation groups. In the pediatric group, only 9 had a C3 value within the target range, and all of them were RAs. The irrevocable interest of isoniazid TDM has been shown in Tunisian patients with tuberculosis, in both adult and pediatric patients, as isoniazid demonstrates an unpredictable pharmacokinetic profile.

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Section: Discussionsupporting

confidence: 92%

Isoniazid Therapeutic Drug Monitoring in Tunisian Patients With Tuberculosis

Alshaikheid

Romdhane

Fredj

et al. 2021

The Journal of Clinical Pharma

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“…The first-line therapy for active tuberculosis consists of daily oral doses of rifampicin, isoniazid, pyrazinamide, and ethambutol, and the treatment for latent tuberculosis consists of a daily oral dose of 5 mg/kg isoniazid (or 15 mg/kg twice weekly). The plasma concentrations of isoniazid were 22-29 mM in a Moroccan population 3 h after administration of rifampicin and isoniazid in patients with active TB infections (Aït Moussa et al, 2016); in another study, the plasma isoniazid C max was between 10 and 50 mM after 6 weeks of rifampicin and isoniazid administration in patients with active TB infections (Aarnoutse et al, 2017). These concentrations in humans were measured in the systemic circulation, whereas the portal and hepatic concentrations of isoniazid would be expected to be several magnitudes higher than that in the systemic circulation and to persist for months.…”

Section: Iron Levels Modulate Human Fech Protein Levelsmentioning

confidence: 99%

The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis

Brewer

Yang

Edwards

et al. 2018

Toxicological Sciences

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In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase in protoporphyrin IX, the penultimate heme precursor. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to upregulate Alas1 but downregulate Fech protein levels in mice; however, the mechanism by which isoniazid mediates disruption of heme synthesis has been unclear. Two metabolites of isoniazid, pyridoxal isonicotinoyl hydrazone (PIH, the isoniazid-vitamin B6 conjugate) and hydrazine, have been detected in the urine of humans treated with isoniazid. Here we show that, in primary human hepatocytes and the human hepatocellular carcinoma cell line HepG2/C3A, (1) isoniazid treatment increases Alas1 protein levels but decreases Fech levels; (2) hydrazine treatment upregulates Alas1 protein and Alas1 mRNA levels; (3) PIH treatment decreases Fech protein levels, but not Fech mRNA levels; and (4) PIH is detected after isoniazid treatment, with levels increasing further when exogenous vitamin B 6 analogs are coadministered. In addition, the PIH-mediated downregulation of human FECH is associated with iron chelation. Together, these data demonstrate that hydrazine upregulates ALAS1, whereas PIH downregulates FECH, suggesting that the metabolites of isoniazid mediate its disruption of heme biosynthesis by contributing to protoporphyrin IX accumulation.

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“…These findings revealed that RFP could cause various types of kidney injuries. Moussa et al compared the blood concentration of RFP in patients with tuberculosis who experienced adverse events [ 31 ], and there was no difference in blood concentration. Since there may be little relationship between the dose and occurrence of adverse events, we should note decreased urine output and anuria regardless of the dose of RFP.…”

Section: Discussionmentioning

confidence: 99%

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

et al. 2022

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Background In Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database. Methods We included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution. Results The total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181–300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3–7.44), 2.61 (95% CI, 1.39–4.91), and 2.38 (95% CI, 1.04–5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62–351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35–14.77) and 6.99 (95% CI, 3.22–15.18). The β value of EB was 2.07 (95% CI, 1.48–2.76), which was classified as a wear-out failure type. Conclusions For MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.

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Rifampicin and isoniazid plasma concentrations in relation to adverse reactions in tuberculosis patients: a retrospective analysis

Cited by 15 publications

References 30 publications

Isoniazid Therapeutic Drug Monitoring in Tunisian Patients With Tuberculosis

Isoniazid Therapeutic Drug Monitoring in Tunisian Patients With Tuberculosis

The Isoniazid Metabolites Hydrazine and Pyridoxal Isonicotinoyl Hydrazone Modulate Heme Biosynthesis

Analysis of adverse drug events in pulmonary Mycobacterium avium complex disease using spontaneous reporting system

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