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. 2020 Nov;86(11):2256-2265.
doi: 10.1111/bcp.14328. Epub 2020 Jun 17.

Amoxicillin-induced crystal nephropathy: A nationwide French pharmacovigilance databases study

Laure Thomas  1 , Christine Le Beller  2 , Thierry Trenque  3 , Joëlle Michot  4 , Marie Zenut  5 , Emmanuel Letavernier  6   7   8 , Nicolas Mongardon  9   10   11 , Dominique Vodovar  12   13   14
Affiliations

Amoxicillin-induced crystal nephropathy: A nationwide French pharmacovigilance databases study

Laure Thomas et al. Br J Clin Pharmacol. 2020 Nov.

Abstract

Aims: Amoxicillin (AMX)-induced crystal nephropathy (AICN) is a rarely reported adverse drug reaction (ADR) but its increase has been recently reported in the Paris area. Our aim was to investigate the incidence, characteristics and outcome of AICN in France.

Methods: Retrospective analysis of all AICN cases reported to the French National Pharmacovigilance Database and the Marketing Authorization Holders Pharmacovigilance Database. AICN notification rate was compared to intravenous AMX and AMX-clavulanate sales.

Results: In total, 101 AICN cases were included. Intravenous AMX/AMX-clavulanate was prescribed as surgical prophylaxis (32 surgical patients) or to treat infection (69 medical patients). AKI KDIGO stage 3 was observed in 70 patients and 24/70 patients required renal replacement therapy and/or intensive care unit admission. The annual notification rate of AICN was increased by a factor of 13 since 2010 (6 [0;7] and 77 [24;111] cases per 100 000 patient-years of exposure, before and after 2010 respectively; P < .001). In surgical patients, the increase in AICN has been reported since 2010 and was mainly related to inadequate AMX administration. In medical patients, the increase in AICN was observed since 2014. After 2014, medical patients were older (67 [42;77] vs 74 years [64;84] respectively; P < .05) and were treated more frequently for endocarditis (0/20 vs 15/49 respectively; P < .01). A contributing factor was observed or suspected in 62 patients.

Conclusion: AICN is a severe ADR that dramatically increased in France since 2010. Assessment of AICN contributing factors and AMX drug monitoring in patients receiving high dose of AMX could reduce the risk of AICN.

Keywords: acute kidney injury; adverse drug reaction; amoxicillin; crystals; renal replacement therapy.

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Conflict of interest statement

The authors have not disclosed any potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Process of AICN case selection. AMX: amoxicillin; CLAV: clavulanate; FNPD: French National Pharmacovigilance Database; MAHPD: marketing authorization holders pharmacovigilance databases; AICN: amoxicillin‐induced crystal nephropathy. *Including 10 cases of crystalluria without AKI or haematuria and 45 cases with AKI but without haematuria
FIGURE 2
FIGURE 2
Trend in amoxicillin‐induced crystal nephropathy (AICN) notification to the French National Pharmacovigilance Database (FNPD) and marketing authorization holders pharmacovigilance databases (MAHPD). Black bar: amoxicillin; white bar: amoxicillin–clavulanate
FIGURE 3
FIGURE 3
Annual notification rate of amoxicillin‐induced crystal nephropathy (AICN) per 100 000 patient‐years of exposure: (A) intravenous amoxicillin (AMX) and/or AMX–clavulanate (AMX‐CLAV; filled circle); (B) intravenous AMX (filled square); (C) intravenous AMX‐CLAV (open square)
See this image and copyright information in PMC

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