PMID- 34762277
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20220612
IS  - 1724-6059 (Electronic)
IS  - 1121-8428 (Linking)
VI  - 35
IP  - 3
DP  - 2022 Apr
TI  - Crystal nephropathy and amoxicillin: insights from international spontaneous 
      reporting systems.
PG  - 1017-1027
LID - 10.1007/s40620-021-01191-y [doi]
AB  - BACKGROUND: A substantial increase in amoxicillin-induced crystal nephropathy was 
      recently reported in France. Our study aims to further characterize this safety 
      issue from a worldwide perspective. METHODS: We queried both the FDA Adverse 
      Event Reporting System (FAERS) and the Eudravigilance databases, and performed 
      disproportionality analysis, selecting only adverse events (AEs) related to 
      crystal nephropathy where amoxicillin or amoxicillin/clavulanic acid were 
      reported as suspect. In FAERS, the reporting odds ratios were calculated and 
      deemed significant by the lower limit of the 95% confidence interval 
      (LL95%CI) > 1, selecting all other drugs/events recorded in FAERS as comparator. 
      Deduplication followed by case-by-case assessment and comparison between French 
      and non-French cases were also performed in both databases. RESULTS: Overall, 
      57,754 and 84,764 AE reports with amoxicillin or amoxicillin/clavulanic acid were 
      recorded in FAERS and Eudravigilance, respectively, with France accounting for 
      18.7% and 22.0% of cases. Specific AEs of interest were retrieved in 144 and 239 
      cases, respectively. Increased reporting was found in FAERS for crystalluria 
      (N = 99; LL95%CI 53.18), crystal nephropathy (24; 27.01), medication crystal in 
      urine present (9; 92.00), crystal urine (8; 11.90), and crystal urine present (4; 
      1.57). In FAERS and Eudravigilance databases, reports were classified as serious 
      in 98.8% and 91.2% of cases, respectively. Acute kidney injury (AKI) was found in 
      81.2% and 71.1% of patients. Amoxicillin was mainly given intravenously, and a 
      dose >/= 12 g/day was administered in 50.0% and 19.7% of cases in the FAERS and 
      Eudravigilance databases, respectively. CONCLUSION: Although causal association 
      cannot be firmly inferred, a consistent signal of crystal nephropathy with 
      amoxicillin emerged, especially in France. Clinicians should monitor patients for 
      possible early AKI onset, especially when dealing with intravenous administration 
      of daily doses > 12 g.
CI  - (c) 2021. Italian Society of Nephrology.
FAU - Gatti, Milo
AU  - Gatti M
AUID- ORCID: 0000-0003-3018-3779
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy. milo.gatti2@unibo.it.
AD  - SSD Clinical Pharmacology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 
      Via Massarenti 9, 40138, Bologna, Italy. milo.gatti2@unibo.it.
FAU - Fusaroli, Michele
AU  - Fusaroli M
AUID- ORCID: 0000-0002-0254-2212
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy.
FAU - Raschi, Emanuel
AU  - Raschi E
AUID- ORCID: 0000-0003-0487-7996
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy.
FAU - Capelli, Irene
AU  - Capelli I
AUID- ORCID: 0000-0003-4829-5664
AD  - Department of Experimental Diagnostic and Specialty Medicine, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy.
AD  - Nephrology Dialysis and Renal Transplant Unit, S. Orsola Hospital, IRCCS Azienda 
      Ospedaliero-Universitaria di Bologna, Bologna, Italy.
FAU - Poluzzi, Elisabetta
AU  - Poluzzi E
AUID- ORCID: 0000-0002-7209-0426
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy.
FAU - De Ponti, Fabrizio
AU  - De Ponti F
AUID- ORCID: 0000-0002-0367-9595
AD  - Pharmacology Unit, Department of Medical and Surgical Sciences, Alma Mater 
      Studiorum - University of Bologna, Bologna, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211111
PL  - Italy
TA  - J Nephrol
JT  - Journal of nephrology
JID - 9012268
RN  - 23521W1S24 (Clavulanic Acid)
RN  - 804826J2HU (Amoxicillin)
SB  - IM
MH  - *Acute Kidney Injury/chemically induced
MH  - Adverse Drug Reaction Reporting Systems
MH  - Amoxicillin/adverse effects
MH  - Clavulanic Acid/adverse effects
MH  - Databases, Factual
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Humans
MH  - Pharmacovigilance
MH  - United States/epidemiology
OTO - NOTNLM
OT  - Acute kidney injury
OT  - Amoxicillin
OT  - Crystal nephropathy
OT  - Pharmacovigilance
OT  - Safety guidance
EDAT- 2021/11/12 06:00
MHDA- 2022/04/13 06:00
CRDT- 2021/11/11 12:29
PHST- 2021/09/08 00:00 [received]
PHST- 2021/10/22 00:00 [accepted]
PHST- 2021/11/12 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2021/11/11 12:29 [entrez]
AID - 10.1007/s40620-021-01191-y [pii]
AID - 10.1007/s40620-021-01191-y [doi]
PST - ppublish
SO  - J Nephrol. 2022 Apr;35(3):1017-1027. doi: 10.1007/s40620-021-01191-y. Epub 2021 
      Nov 11.