loading page

Discovering Interactions in polypharmacy: Impact of Metamizole on the Metabolism of Quetiapine
  • +4
  • Fabian Watermeyer,
  • Arnim Johannes Gaebler,
  • Irene Neuner,
  • Ekkehard Haen,
  • Christoph Hiemke,
  • Georgios Schoretsanitis,
  • Michael Paulzen
Fabian Watermeyer
RWTH Aachen University
Author Profile
Arnim Johannes Gaebler
RWTH Aachen University
Author Profile
Irene Neuner
RWTH Aachen University
Author Profile
Ekkehard Haen
Psychiatric Hospital of the University of Regensburg
Author Profile
Christoph Hiemke
University Medical Center of Mainz
Author Profile
Georgios Schoretsanitis
University of Zurich
Author Profile
Michael Paulzen
RWTH Aachen University

Corresponding Author:[email protected]

Author Profile


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 2023Assigned to Editor
13 Jun 2023Submission Checks Completed
13 Jun 2023Review(s) Completed, Editorial Evaluation Pending
04 Jul 2023Reviewer(s) Assigned