Severe reduction in tacrolimus concentrations with concomitant metamizole (dipyrone) therapy in transplant patients

  • Ali SigaroudiEmail author
  • Alexander Jetter
  • Thomas F. Mueller
  • Gerd Kullak-Ublick
  • Stefan Weiler
Letter to the Editor

To the Editors:

Tacrolimus is a substrate of cytochrome (CYP) 3A4/3A5 and P-glycoprotein (Pgp) and its use therefore entails the risk for drug–drug interactions. The analgesic drug metamizole (dipyrone) has shown in vitro potential as an inducer of CYP2B6 and CYP3A4 [1]. Furthermore, in an in vivo study a short-term administration of metamizole decreased the blood concentrations of cyclosporine (which is also a substrate of CYP3A4/3A5) with a latency of few hours [2]. However, cyclosporine, in contrast to tacrolimus, is more intensively metabolized by CYP3A4 than by CYP3A5 [3]. In the Swiss medicinal product information of tacrolimus supplied by the Swiss federal drug authority (Swissmedic) it is stated that metamizole is able to decrease tacrolimus’ drug concentrations [4]. Yet, no case reports of co-administration of metamizole and tacrolimus have been published.

From March to December 2017, the Regional Pharmacovigilance Centre (RPVC) Zurich received five reports on decreased...


Compliance with ethical standards

Conflicts of interest

All authors declare that there are no conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Clinical Pharmacology and ToxicologyUniversity Hospital Zurich–University of ZurichZurichSwitzerland
  2. 2.Institute of PharmacogeneticsUniversity of Duisburg-Essen and Essen University HospitalEssenGermany
  3. 3.Division of NephrologyUniversity Hospital Zurich–University of ZurichZurichSwitzerland
  4. 4.Tox Info Suisse, National Poison CentreAssociated Institute of the University of ZurichZurichSwitzerland

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