Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions.
Fatal opioid toxicity occurred in a developmentally delayed child aged 5 years 9 months who was inadvertently administered high doses of hydrocodone for a respiratory tract infection. The concentration of hydrocodone in postmortem blood was in the range associated with fatality; however, hydromorphone, a major metabolite catalyzed by cytochrome P450 2D6 (CYP2D6), was not detected when using mass spectrometry. Genetic analysis revealed that the child had a reduced capability to metabolize the drug via the CYP2D6 pathway (CYP2D6*2A/*41). Coadministration of clarithromycin (a potent cytochrome P450 3A4 inhibitor) for an ear infection and valproic acid for seizures since birth further prevented drug elimination from the body. This case highlights the interplay between pharmacogenetic factors, drug-drug interactions, and dose-related toxicity in a child.
Madadi
Parvaz
P
Motherisk Program, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8.
Hildebrandt
Doris
D
Gong
Inna Y
IY
Schwarz
Ute I
UI
Ciszkowski
Catherine
C
Ross
Colin J D
CJ
Sistonen
Johanna
J
Carleton
Bruce C
BC
Hayden
Michael R
MR
Lauwers
Albert E
AE
Koren
Gideon
G
D000996:Antitussive Agents / Q000493:pharmacokinetics / Q000506:poisoning* / Q000627:therapeutic use; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D004347:Drug Interactions; D062787:Drug Overdose; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000493:pharmacokinetics / Q000506:poisoning* / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use
D000996:Antitussive Agents; D014635:Valproic Acid; D006853:Hydrocodone; D019389:Cytochrome P-450 CYP2D6