Advertisement

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
  • 23 Downloads

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...

Notes

Compliance with ethical standards

Conflicts of interest

All authors declare that there are no conflicts of interest.

References

  1. 1.
    Saussele T, Burk O, Blievernicht JK, Klein K, Nussler A, Nussler N, Hengstler JG, Eichelbaum M, Schwab M, Zanger UM. Selective induction of human hepaticcytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther 2007;82(3):265-74Google Scholar
  2. 2.
    Caraco Y, Zylber-Katz E, Fridlander M, Admon D, Levy M (1999) The effect of short-term dipyrone administration on cyclosporin pharmacokinetics. Eur J Clin Pharmacol 55(6):475–478CrossRefGoogle Scholar
  3. 3.
    Hebert MF (1997) Contributions of hepatic and intestinal metabolism and P-glycoprotein to cyclosporine and tacrolimus oral drug delivery. Adv Drug Deliv Rev 27(2–3):201–214CrossRefGoogle Scholar
  4. 4.
    Astellas Pharma AG. Product information Prograf©. Available from www.swissmedicinfo.ch. Accessed 25 July 2018
  5. 5.
    Tang W, Stearns RA (2001) Heterotropic cooperativity of cytochrome P450 3A4 and potential drug-drug interactions. Curr Drug Metab 2(2):185–198 ReviewCrossRefGoogle Scholar
  6. 6.
    Kasicka-Jonderko A, Nita A, Jonderko K, Kamińska M (2011) Błońska-Fajfrowska B. C-methacetin breath test reproducibility study reveals persistent CYP1A2 stimulation on repeat examinations. World J Gastroenterol 17(45):4979–4986CrossRefGoogle Scholar
  7. 7.
    Dai Y, Hebert MF, Isoherranen N, Davis CL, Marsh C, Shen DD, Thummel KE (2006) Effect of CYP3A5 polymorphism on tacrolimus metabolic clearance in vitro. Drug Metab Dispos 34(5):836–847CrossRefGoogle Scholar
  8. 8.
    Wang J, Li K, Zhang X, Teng D, Ju M, Jing Y, Zhao Y, Li G (2017) The correlation between the expression of genes involved in drug metabolism and the blood level of tacrolimus in liver transplant receipts. Sci Rep 7(1):3429CrossRefGoogle Scholar
  9. 9.
    Maldonado AQ, Asempa T, Hudson S, Rebellato LM (2017) Prevalence of CYP3A5 genomic variances and their impact on Tacrolimus dosing requirements among kidney transplant recipients in eastern North Carolina. Pharmacotherapy 37(9):1081–1088CrossRefGoogle Scholar

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

Personalised recommendations