Risk of kidney injury in patients on concomitant oral vancomycin and piperacillin‐tazobactam: Analysis of the pharmacovigilance database in Japan

Abstract: The U.S. Food and Drug Administration (FDA) has stated that the prescription of remdesivir should be cautious for patients with estimated glomerular filtration rate (eGFR) < 30 and some studies reported risk of adverse renal events. The available information on the renal safety profile for remdesivir is limited, thus we analyzed the renal and urinary adverse reactions attributed to remdesivir reported in a large open pharmacovigilance database. We obtained reports of remdesivir and other drugs used to treat COVID-19 (tocilizumab, hydroxychloroquine, lopinavir/ritonavir) registered by September 30 2020, from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). We analyzed the reporting odds ratios (RORs) for reports of adverse renal and urinary events for remdesivir and other drugs. We found 2,922 reports with remdesivir registered in FAERS for COVID-19. Among these, 493 renal and urinary adverse effects (16.9%) were reported. The most frequent events were acute kidney injury (338; 11.6%), renal impairment (86; 2.9%), and renal failure (53; 1.8%). Versus hydroxychloroquine, lopinavir/ritonavir, or tocilizumab, the use of remdesivir was associated with an increased chance of reporting renal and urinary disorders regardless of gender and age of patients (2.53; 95%CI: 2.10-3.06). The ROR remained significant when we restricted the analysis to hydroxychloroquine (4.31; 95%CI: 3.25-5.71) or tocilizumab (3.92; 95%CI: 2.51-6.12). Our results reinforce this already reported signal, emphasizing that it could be extremely useful for health professionals who prescribe this new antiviral to treat COVID-19, mainly knowing its low efficacy.

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Acute kidney injury associated with febuxostat and allopurinol: a post-marketing study

Arthritis Research & Therapy ◽

10.1186/s13075-019-2011-y ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Amayelle Rey ◽

Benjamin Batteux ◽

Solène M. Laville ◽

Justine Marienne ◽

Kamel Masmoudi ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Kidney Injury ◽

Renal Stones ◽

World Health ◽

Sensitivity Analyses ◽

Reporting Odds Ratio ◽

Pharmacovigilance Database ◽

Post Marketing ◽

Medical Dictionary

Abstract Background For patients with recurrent flares of gout, tophi, urate crystal arthropathy, and renal stones, urate-lowering therapies (ULTs, including allopurinol and febuxostat) are the first-line treatment. Due to the widespread use of these ULTs (especially in patients with impaired renal function), assessment of the associated renal risk is essential. Accordingly, we performed a disproportionality analysis of reported cases of acute renal failure (ARF) associated with allopurinol and febuxostat. Methods We carried out a case/non-case study of the World Health Organization’s VigiBase® pharmacovigilance database between January 1, 2008, and December 31, 2018. The frequency of reports of ARF as a standardized Medical Dictionary for Regulatory Activities query for allopurinol and febuxostat was compared with that of all other reports for the two drugs and quoted as the reporting odds ratio (ROR) [95% confidence interval (CI)]. The results’ stability was assessed in a series of sensitivity analyses (notably after the exclusion of putative competing drugs). Results Among 3509 “suspected drug” notifications for febuxostat and 18,730 for allopurinol, we identified respectively 317 and 1008 cases of ARF. Acute renal failure was reported significantly more frequently for febuxostat and allopurinol than for other drugs (ROR [95%CI] 5.67 [5.05–6.36] and 3.25 [3.05–3.47], respectively). For both drugs, the ROR was higher in women than in men, respectively 11.60 [9.74–13.82] vs. 3.14 [2.69–3.67] for febuxostat and 4.45 [4.04–4.91] vs. 2.29 [2.11–2.50] for allopurinol. The sensitivity analyses confirmed the disproportionality for these two ULTs. Conclusions Acute renal failure was reported respectively 5.7 and 3.3 times more frequently for febuxostat and for allopurinol than for other drugs. Due to the potential consequences of ARF, physicians should take account of this disproportionality signal when prescribing the ULTs febuxostat and allopurinol.

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A Prospective Pilot Study on the Systemic Absorption of Oral Vancomycin in Children With Colitis

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-21.5.426 ◽

2016 ◽

Vol 21 (5) ◽

pp. 426-431 ◽

Cited By ~ 3

Author(s):

James W. Antoon ◽

Margaret Hall ◽

Diana Metropulos ◽

Michael J. Steiner ◽

Ravi Jhaveri ◽

...

Keyword(s):

Kidney Injury ◽

Serum Levels ◽

Systemic Absorption ◽

Severe Illness ◽

Oral Vancomycin ◽

The North ◽

Red Man Syndrome ◽

Serial Serum ◽

Serum Vancomycin ◽

Severe Colitis

BACKGROUND: Oral vancomycin is used to treat refractory colitis due to Clostridium dificile infection. Traditionally, oral vancomycin was thought to not be absorbed systemically, but recent adult studies have demonstrated detectable serum levels in over half of patients with severe colitis. This has not been studied in children. OBJECTIVE: To determine the absorption of oral vancomycin and the renal safety profile of oral vancomycin in children hospitalized with colitis. METHODS: We performed a prospective, observational, pilot proof of principle study at the North Carolina Children's Hospital in patients 2 years to 18 years of age receiving oral vancomycin for the treatment of C dificile colitis. Severity of disease was determined using a validated scoring system. Serial serum vancomycin levels and renal function tests were performed during the administration of oral vancomycin. RESULTS: All patients enrolled (n = 8) had mild to moderate C dificile colitis and varying severity of underlying systemic diseases; 7 with inflammatory bowel disease and 1 with acute kidney injury following renal transplantation. No enrolled patients had detectable levels of serum vancomycin. Additionally, no adverse renal outcomes were attributed to oral vancomycin, and no cases of “Red Man” syndrome were observed. CONCLUSIONS: Unlike studies in adult patients, oral vancomycin is likely not absorbed in children with mild to moderate colitis. Further study is needed to determine the pharmacokinetics in severe colitis and those with severe illness in a critical care setting.

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