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\begin{document}

\title{Discovering Interactions in polypharmacy: Impact of Metamizole on the
Metabolism of Quetiapine}



\author[1]{Fabian Watermeyer}%
\author[1]{Arnim Johannes Gaebler}%
\author[1]{Irene Neuner}%
\author[2]{Ekkehard Haen}%
\author[3]{Christoph Hiemke}%
\author[4]{Georgios Schoretsanitis}%
\author[1]{Michael Paulzen}%
\affil[1]{RWTH Aachen University}%
\affil[2]{Psychiatric Hospital of the University of Regensburg}%
\affil[3]{University Medical Center of Mainz}%
\affil[4]{University of Zurich}%


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  \date{May 25, 2024}


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\begin{abstract}
Objective: Metamizole is quite an old drug with analgesic, antipyretic
and spasmolytic properties. Recent findings have shown that it may
induce several cytochrome P450 enzymes, especially CYP3A4 and CYP2B6.
The clinical relevance of these properties is uncertain. We aimed to
unravel potential pharmacokinetic interactions between metamizole and
the CYP3A4 substrate quetiapine. Methods: Plasma concentrations of
quetiapine from a large therapeutic drug monitoring database were
analyzed. Two groups of 33 patients, either receiving quetiapine as a
monotherapy (without CYP modulating co-medications) or with
concomitantly applied metamizole were compared addressing a potential
impact of metamizole on the metabolism of quetiapine being reflected in
differences of plasma concentrations of quetiapine and dose-adjusted
plasma concentrations (C/D). Results: Patients co-medicated with
metamizole showed significantly lower plasma concentrations of
quetiapine (median 45.2 ng/mL, Q1=15.5; Q3=90.5 vs. 92.0 ng/mL, Q1=52.3;
Q3=203.8, p=0.003). Accordingly, plasma concentrations of quetiapine in
the control group were more than twice of those in the metamizole group
(+103\% higher). The dose-adjusted plasma concentrations were 69 \%
lower in the co-medication group (p=0.001). Conclusions: The combination
of metamizole and quetiapine leads to significantly lower drug
concentrations of quetiapine, most likely via an induction of cytochrome
P450 CYP3A4 by metamizole. Clinicians have to consider the risk of
adverse drug reactions, especially treatment failure under quetiapine
when adding metamizole.%
\end{abstract}%



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