RESUMEN
OBJECTIVE: To quantify the incidence of central nervous system (CNS) depression in neonates breastfed by mothers medicated with oxycodone as compared with neonates whose breastfeeding mothers used codeine or acetaminophen only. STUDY DESIGN: We retrospectively compared 3 cohorts in 533 breastfeeding mother-infant pairs exposed to oxycodone (n = 139), codeine (n = 210), or acetaminophen only (n = 184). Standardized questionnaires were administered to mothers during the postpartum period to identify maternal and neonatal health outcomes temporally related to analgesia exposure. RESULTS: Maternal exposure to oxycodone during breastfeeding was associated with a 20.1% rate of infant CNS depression (28/139) compared with 0.5% in the acetaminophen group (1/184; P < .0001; OR, 46.16; 95% CI, 6.2-344.2) and 16.7% in the codeine group (35/210; P > .05; OR, 0.79; 95% CI, 0.46-1.38). Mothers of neonates with symptoms in the oxycodone and codeine cohorts took significantly higher doses of medication compared with mothers of infants with no symptoms in the same cohorts (P = .0005 oxycodone; median, 0.4 mg/kg/day; range, 0.03-4.06 mg/kg/day versus median, 0.15 mg/kg/day; range, 0.02-2.25 mg/kg/day; codeine P < .001; median, 1.4 mg/kg/day; range, 0.7-10.5 mg/kg/day versus 0.9 mg/kg/day; range, 0.18-5.8 mg/kg/day). Mothers were significantly more likely to experience sedative adverse effects from oxycodone as compared with codeine (P < .0001; OR, 17.62; 95% CI, 9.95-31.21). CONCLUSION: Oxycodone is not a safer alternative to codeine in breastfed infants.
Asunto(s)
Acetaminofén/efectos adversos , Analgesia , Analgésicos no Narcóticos/efectos adversos , Analgésicos Opioides/efectos adversos , Lactancia Materna , Sistema Nervioso Central/efectos de los fármacos , Codeína/efectos adversos , Letargia/inducido químicamente , Oxicodona/efectos adversos , Periodo Posparto , Adulto , Femenino , Humanos , Incidencia , Recién Nacido , Letargia/epidemiología , Estudios RetrospectivosAsunto(s)
Adenoidectomía , Analgésicos Opioides/metabolismo , Codeína/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Morfina/sangre , Complicaciones Posoperatorias , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/sangre , Bronconeumonía/complicaciones , Preescolar , Codeína/administración & dosificación , Codeína/sangre , Citocromo P-450 CYP2D6/genética , Resultado Fatal , Genotipo , Humanos , Masculino , Síndromes de la Apnea del Sueño/cirugía , TonsilectomíaRESUMEN
The pro-drug codeine is commonly prescribed for postpartum pain relief in North America. The safety of codeine during breastfeeding is related in part to the extent of the active morphine metabolite catalyzed from codeine via the cytochrome P450 2D6 (CYP2D6) enzyme. In mothers who have greater than two functional copies of the CYP2D6 gene (CYP2D6 ultrarapid metabolism phenotype; UM) a substantially higher proportion of morphine is produced. Label changes on codeine-containing medications will highlight the risks associated with this genotype for breastfeeding mothers, but are not supported by translation strategies on how to incorporate this pharmacogenetic knowledge into clinical practice. To address the immediate issue of CYP2D6 UM inheritance in family members of a breastfed infant who succumbed to fatal opioid intoxication and whose codeine-prescribed mother was a CYP2D6 UM, we constructed a pedigree. While the pedigree approach is helpful to aid diagnosis, identify other at risk family members, and simplify pharmacogenetic analysis, its clinical usefulness is dependant on an institutional framework which is not available in most centers at this time.
Asunto(s)
Lactancia Materna , Codeína/efectos adversos , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Leche Humana/enzimología , Codeína/administración & dosificación , Codeína/biosíntesis , Femenino , Humanos , Lactante , Linaje , FenotipoRESUMEN
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.