A comparative study of efficacy and safety of febuxostat and allopurinol in pyrazinamide-induced hyperuricemic tubercular patients

Pichholiya, Meenu; Yadav, Arvind Kumar; Luhadia, Shanti Kumar; Tahashildar, Jameela; Aseri, M L

doi:10.4103/0253-7613.190729

Cited by 6 publications

(1 citation statement)

References 15 publications

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“…PZA is an indispensable frst-line drug in the treatment of TB, and its most common adverse reaction is elevated SUA. Te initial symptoms of SUA elevation are often not obvious and easily ignored, which brings potential safety risks for clinical treatment [14], but the incidence was reported to be as high as 43% to 100% [3,15]. Te induction mechanism might involve the PZA metabolite pyrazinic acid, which increases uric acid reabsorption at the brush-like boundary of proximal curved tubules [4].…”

Section: Discussionmentioning

confidence: 99%

SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

Dai

Wang

Wu³

et al. 2023

Journal of Clinical Pharmacy and Therapeutics

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What Is Known and Objective. Elevated serum uric acid (SUA) is one of the most common adverse reactions during the administration of pyrazinamide, but patients exhibit significant individual differences. This study aimed to evaluate the relationship between gene polymorphisms and pyrazinamide-induced SUA elevation in Han Chinese tuberculosis patients. Methods. Tuberculosis patients treated with pyrazinamide were genotyped for the following three candidate genes: SLC22A12, SLC2A9, and ABCG2. Patients were divided into low-risk and high-risk groups according to the change of SUA after treatment. Intergroup comparisons were performed on clinical characteristics, allele and genotype frequencies, and haplotype distributions, and logistic regression analysis was used to explore the relevant risk factors. Results. In total, 143 patients were enrolled, including 83 in the high-risk groups and 60 in the low-risk groups. We observed a significant association between SLC2A9 polymorphism and pyrazinamide-induced SUA elevation. The G allele was significantly lower in the high-risk group than in the low-risk group (27.7% vs. 48.3%, OR = 0.410, 95% CI: 0.250–0.671, p < 0.001 ). Patients with the GA and GG genotypes were less likely to have SUA elevation than those with the AA genotype (OR = 0.125, 95% CI: 0.053–0.293, p < 0.001 and OR = 0.252, 95% CI: 0.074–0.851, p = 0.026 , respectively). Regarding SLC2A9 rs13129697, the frequency of the G allele was significantly lower in the high-risk group than in the low-risk group (26.1% vs. 40.8%, OR = 0.531, 95% CI: 0.312–0.842, p = 0.008 ). In the low-risk group, the proportion of patients with the TG genotype was significantly higher than that with the TT genotype (81.7% vs. 18.3%, OR = 0.279, 95% CI: 0.127–0.611, p = 0.001 ). Haplotype analysis revealed that patients with the SLC2A9 (rs1014290–rs13129697) GG haplotype had lower risk of SUA elevation than those with the AT haplotype (27.11% vs. 63.25%, p = 0.005 ). Furthermore, logistic regression analysis showed that drinking history was an independent risk factor for elevated SUA caused by PZA (OR = 3.943, 95% CI = 1.18–13.175, p = 0.026 ) and that the rs1014290 GA genotype might be a protective factor (OR = 0.094, 95% CI = 0.023–0.386, p = 0.001 ) after correction. What Is New and Conclusion. We found that SLC2A9 genetic polymorphisms were associated with elevated SUA caused by pyrazinamide. The G>A variant of rs1014290 and drinking history might be risk factors.

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Section: Discussionmentioning

confidence: 99%

SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

Dai

Wang

Wu³

et al. 2023

Journal of Clinical Pharmacy and Therapeutics

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Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection

Kim

Kang

Whang³

et al. 2022

Antimicrob Agents Chemother

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Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis

et al. 2021

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Aims To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. Methods and results Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT’s a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT’s and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l). Conclusions Data from RCT’s and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia. Systematic review registration PROSPERO registration CRD42018089744

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A comparative study of efficacy and safety of febuxostat and allopurinol in pyrazinamide-induced hyperuricemic tubercular patients

Cited by 6 publications

References 15 publications

SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

SLC2A9 Gene Polymorphism Is Associated with Elevated Serum Uric Acid Caused by Pyrazinamide

Novel Antibacterial Activity of Febuxostat, an FDA-Approved Antigout Drug against Mycobacterium tuberculosis Infection

Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis

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