Phenytoin intoxication associated with omeprazole administration in a child with defective CYP2C9

  • M. MaranoEmail author
  • F. Nicoletti
  • S. Pro
  • B. M. Goffredo
  • C. Cecchetti
  • E. Piervincenzi
  • E. Agolini
  • D. Cocciadiferro
Letter to the Editor


Adverse drug reactions occur at a high rate in hospitalized children, frequently due to antiepileptic drug administration. Phenytoin is a commonly used drug, and its metabolism is mediated by a specific cytochrome-P450 isoform, CYP2C9, which is encoded by a polymorphic gene. It is worth noting that very frequently administered drugs, such as proton pump inhibitors, compete with phenytoin for CYP2C19-mediated metabolism. Here we describe a case of phenytoin intoxication in a child with defective CYP2C9, after omeprazole administration.


Phenytoin Adverse drug reactions Omeprazole CYP2C9 CYP2C19 


Compliance with ethical standards

Conflict of interest



Informed consent was given by the patient’s legal guardians for the publication of this study.


  1. 1.
    Elzagallaai AA, Greff M, Rieder MJ (2017 Jun) Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics. Clin Pharmacol Ther. 101(6):725–735CrossRefGoogle Scholar
  2. 2.
    Kochanek PM, Tasker RC, Carney N et al (2019) Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines. Executive Summary. Neurosurgery. 84(6):1169–1178PubMedGoogle Scholar
  3. 3.
    Silvado CE, Terra VC, Twardowschy CA (2018) CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment. Pharmgenomics Pers Med. 11:51–58PubMedPubMedCentralGoogle Scholar
  4. 4.
    Wedemeyer RS, Blume H (2014) Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 37(4):201–211CrossRefGoogle Scholar
  5. 5.
    Gugler R, Jensen JC (1985) Omeprazole inhibits oxidative drug metabolism. Studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology. 89(6):1235–1241CrossRefGoogle Scholar
  6. 6.
    Regårdh CG, Gabrielsson M, Hoffman KJ et al (1985) Pharmacokinetics and metabolism of omeprazole in animals and man: an overview. Scand J Gastroenterol Suppl. 108:79–94CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.DEA Paediatric Intensive Care Unit, IRCCS Bambino Gesù Children’s HospitalRomeItaly
  2. 2.Regional Paediatric Poison Center, IRCCS Bambino Gesù Children’s HospitalRomeItaly
  3. 3.Department of Physiology and PharmacologyUniversity Sapienza of RomeRomeItaly
  4. 4.IRCCS NeuromedPozzilliItaly
  5. 5.Neurology Unit, Department of Neurosciences, IRCCS, Bambino Gesù Children’s HospitalRomeItaly
  6. 6.Department of Pediatric Medicine, Laboratory of Metabolic Biochemistry Unit, IRCCS, Bambino Gesù Children’s HospitalRomeItaly
  7. 7.Department of Anaesthesia and Critical Care MedicineUniversity Sapienza of RomeRomeItaly
  8. 8.Laboratory of Medical Genetics, Bambino Gesù Children’s HospitalRomeItaly

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