Dramatic Increase of Amoxicillin-Induced Crystal Nephropathy Found in a Cohort Study of French Pharmacovigilance Centers

Abstract

An increase in amoxicillin-induced crystal nephropathy (AICN) incidence has been recently suggested. The aims of this study were to investigate the trend of AICN incidence through Paris' regional centers of pharmacovigilance (Paris RCPVs) and better describe this rare adverse drug reaction. Forty-five AICN cases were identified between 1985 and 2016. All cases, except one, were reported since 2010. Amoxicillin (AMX) was administered intravenously (65 [interquartile range {IQR}, 43 to 110] mg/kg of body weight/day) in all patients, either for treating infection ( = 15) or as surgical prophylaxis ( = 30). Delay between AMX administration and AICN onset was 1 (IQR, 1 to 3) day; 30, 4, and 11 patients developed KDIGO stage 1, 2, and 3 acute kidney injury, respectively. Delay between AICN onset and kidney function recovery was 4 (IQR, 2 to 6) days. Precipitating factors were identified in only one-third of cases. Twelve patients required intensive care unit admission, and 8 needed renal replacement therapy. Neither chronic kidney disease nor death was observed. We confirmed the recent and dramatic increase of AICN in the Paris RCPVs since 2010. The absence of precipitating factors in the majority of cases and the onset of AICN in apparent routine indications, such as surgical prophylaxis, are alarming and justify a high vigilance from all AMX prescribers.

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center

“…In addition, targeting f TϾMIC of 100% in all burn patients would require larger doses and concentrations of amoxicillin that could increase its toxicity without a thorough monitoring by TDM. Indeed, adverse reactionsm such as crystalluria, have been reported with the use of high doses of amoxicillin (37,38). Unlike renal function, interindividual changes in BW did not appear to have a clinically relevant influence on amoxicillin PD in adult burn patients.…”

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

“…the precipitation of crystals of AMX in urine-is a well-known but rarely reported ADR. 3,4 While some patients remain asymptomatic, AMX-induced crystalluria may be responsible for haematuria associated with acute kidney injury (AKI). 5 Amoxicillin-induced crystal nephropathy (AICN) is related to the obstruction of the ureter and/or renal tubules by AMX crystals.…”

“…5,6 AICN onset may be responsible for life-threatening complications and may require renal replacement therapy (RRT). 4,7 Although the oral route of AMX or AMX-CLAV administration has been associated with AICN, most recently published AICN cases were associated with the intravenous route. [4][5][6][7][8][9][10][11] Several contributing factors for AICN have been suspected and include: high dose and/or too fast intravenous administration and/or administration of highly-concentrated solution of AMX, acid urine pH and dehydration.…”

“…4,7 Although the oral route of AMX or AMX-CLAV administration has been associated with AICN, most recently published AICN cases were associated with the intravenous route. [4][5][6][7][8][9][10][11] Several contributing factors for AICN have been suspected and include: high dose and/or too fast intravenous administration and/or administration of highly-concentrated solution of AMX, acid urine pH and dehydration. 3,4,6 Recently, an increase in AICN associated with the prescription of intravenous AMX/AMX-CLAV has been observed in the Paris area in France.…”

“…[4][5][6][7][8][9][10][11] Several contributing factors for AICN have been suspected and include: high dose and/or too fast intravenous administration and/or administration of highly-concentrated solution of AMX, acid urine pH and dehydration. 3,4,6 Recently, an increase in AICN associated with the prescription of intravenous AMX/AMX-CLAV has been observed in the Paris area in France. It was first reported by a single hospital in Paris and further confirmed at the regional level by studying AICN cases reported to the regional centres of pharmacovigilance (RCPVs) of the Paris area.…”