Drug dosing error with drops—severe clinical course of codeine intoxication in twins

  • Maren Hermanns-Clausen
  • Wolfgang Weinmann
  • Volker Auwärter
  • Nerea Ferreirós
  • Rainer Trittler
  • Christoph Müller
  • Andreas Pahl
  • Andrea Superti-Furga
  • Roland Hentschel
Original Paper

DOI: 10.1007/s00431-008-0842-7

Cite this article as:
Hermanns-Clausen, M., Weinmann, W., Auwärter, V. et al. Eur J Pediatr (2009) 168: 819. doi:10.1007/s00431-008-0842-7

Abstract

In spite of the lack of evidence for its efficacy, and of sporadic reports of severe adverse events, codeine is still widely used as an antitussive agent in children. A 3-year-old boy (twin 1) was found lying in vomit and apnoeic at night; he was resuscitated and immediately transferred to our paediatric intensive care unit (PICU). Two and a half hours later, his twin brother (twin 2) was found dead in his bed at home. Twin 1 required mechanical ventilation for 3 days, but he eventually made a full recovery; autopsy in twin 2 showed massive aspiration of gastric content. History revealed that the monozygotic twins had an upper respiratory tract infection for several days and had both been given codeine at a dose of “10 drops per day” by their mother. The blood of both twins was found to contain high levels of codeine and its metabolites. The weight of “10 drops” was determined experimentally and was found to range from 494 to 940 mg. Thus, the highest possible dose given by mother was 23.5 mg of codeine instead of the recommended 10 mg. The twins had identical CYP2D6 gene polymorphisms corresponding to the “extensive metaboliser” type. Conclusions: Because of the variability of drop size drug dosage, dosage “by drops” is unprecise and may result in accidental overdose. The combination of repeated overdosing and extensive metabolism to morphine is likely to have caused apnoea in these twins. These cases illustrate the danger of codeine as an antitussive in young children.

Keywords

CodeineExtensive metaboliserDosing errorIntoxication

Abbreviations

M6G

Morphin-6-glucuronide

M3G

Morphin-3-glucuronide

UM

Ultrarapid metabolism

EM

Extensive metabolism

PM

Poor metabolism

UDP-GT

Uridine diphosphate-glucuronosyltransferase

CYP

Cytochrom P450

GCS

Glasgow Coma Scale

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Maren Hermanns-Clausen
    • 1
  • Wolfgang Weinmann
    • 2
  • Volker Auwärter
    • 2
  • Nerea Ferreirós
    • 2
  • Rainer Trittler
    • 3
  • Christoph Müller
    • 4
  • Andreas Pahl
    • 5
  • Andrea Superti-Furga
    • 4
  • Roland Hentschel
    • 4
  1. 1.Poison Information Center VIZ-FreiburgCenter for Paediatrics and Adolescent MedicineFreiburgGermany
  2. 2.Institute of Forensic MedicineFreiburg University HospitalFreiburgGermany
  3. 3.University Hospital PharmacyFreiburgGermany
  4. 4.Center for Paediatrics and Adolescent MedicineFreiburg University HospitalFreiburgGermany
  5. 5.Institute of Experimental and Clinical PharmacologyErlangen-NuernbergGermany