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Fatal hydrocodone overdose in a child: pharmacogenetics and drug interactions
Parvaz Madadi1, Doris Hildebrandt, Inna Y Gong
1Motherisk Program, Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, 555 University Ave, Toronto, ON, Canada M5G 1X8.
Abstract:
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.
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