Drug dosing using estimated glomerular filtration rate: Misclassification due to metamizole interference in a creatinine assay

Abstract

The estimated glomerular filtration rate is a rather important measurement for patients under intensive care, since they often receive several drugs, and impaired renal function may result in misleading dosing. The estimated glomerular filtration is derived from mathematical models using serum creatinine, a measurement that suffers interference of some drugs, such as metamizole. The study intented to evaluate the impact on patient stratification for dose adjustment of two antimicrobials (meropenem and vancomycin) caused by metamizole interference in creatinine measurement by dry chemistry. A cross-sectional study was conducted with a group of 108 hospitalized patients under metamizole prescriptions at fixed intervals. Serum creatinine levels were determined by enzymatic dry chemistry and Jaffé assays and the estimated glomerular filtration rate was calculated through the CKD-EPI equation. Patients were stratified in groups according to their estimated glomerular filtration rate for drug dosing of vancomycin and meropenem. As expected, creatinine values were significantly lower in measurements performed by the dry chemistry method in comparison to Jaffé assay (p<0.0001) when patients are under metamizole treatment. A significant bias (-40.3%) was observed between those two methods, leading to a significant difference (p<0.0001) in patient classification according to renal function using the CKD-EPI equation for dosing adjustment. Thus, during the validity of metamizole treatment, the stratification for drug dosing by the estimated glomerular filtration rate is not reliable if the creatinine measurement is done through dry chemistry. Clinical and laboratory staff must be aware of these limitations and cooperate to optimize pharmacotherapy.

Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial

“…Our trial has several limitations. Due to the lack of supplies during the pandemic, glomerular filtration was assessed using creatinine levels calculated by dry chemistry method, which suffers interference by dipyrone (metamizole), drug widely administered to fever and pain control 31 . Other limitations of the study included: study conducted in a single center and phone monitoring of patients discharged from hospital until the end of EPP-AF treatment period (10 days).…”

Bayesian Models for Therapeutic Monitoring of Vancomycin in the Critically Ill: What Should They Predict?

“…Subtherapeutic concentrations were measured in 68% of adults, in 76% of children, and in 52% of neonates after treatment initiation (2). In addition to human factors, which should not be ignored, immunoassays, used for drug monitoring of vancomycin, are susceptible to cross-reactivity secondary to endogenous protein or some drug interference (3).…”

Emergency medicine pharmacotherapy compromises accuracy of plasma creatinine determination by enzyme-based methods: real-world clinical evidence and implications for clinical practice

“…During the past two decades, Jaffé methods have been widely replaced by enzyme-based colorimetric methods employing sarcosine oxidase/peroxidase reaction chemistry ( 2 ). It has been shown repeatedly that enzymatic methods are susceptible to negative interference caused by several drugs, such as etamsylate ( 3 ), metamizole ( 4 , 5 ), paracetamol, N-acetyl-p-benzoquinone imine (NAPQUI) ( 5 ), acetylcysteine ( 6 ), derivatives of salicylic acid ( 5 , 7 ), high-dose acidum ascorbicum ( 8 ), and dobesilate ( 9 ). Negative interference by catecholamines at clinically relevant concentrations was also shown to affect these methods ( 10 ), and recently, monoclonal immunoglobulins have also been reported to interfere ( 11 , 12 ).…”