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Discovering Interactions in polypharmacy: Impact of Metamizole on the Metabolism of Quetiapine
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  • Fabian Watermeyer,
  • Arnim Johannes Gaebler,
  • Irene Neuner,
  • Ekkehard Haen,
  • Christoph Hiemke,
  • Georgios Schoretsanitis,
  • Michael Paulzen
Fabian Watermeyer
RWTH Aachen University
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Arnim Johannes Gaebler
RWTH Aachen University
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Irene Neuner
RWTH Aachen University
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Ekkehard Haen
Psychiatric Hospital of the University of Regensburg
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Christoph Hiemke
University Medical Center of Mainz
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Georgios Schoretsanitis
University of Zurich
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Michael Paulzen
RWTH Aachen University

Corresponding Author:[email protected]

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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.
11 Jun 2023Submitted to British Journal of Clinical Pharmacology
13 Jun 2023Submission Checks Completed
13 Jun 2023Assigned to Editor
13 Jun 2023Review(s) Completed, Editorial Evaluation Pending
04 Jul 2023Reviewer(s) Assigned
14 Apr 2024Editorial Decision: Revise Major
02 Jun 20241st Revision Received
03 Jun 2024Submission Checks Completed
03 Jun 2024Assigned to Editor
03 Jun 2024Review(s) Completed, Editorial Evaluation Pending
06 Jun 2024Editorial Decision: Accept