Asunto(s)
Antidepresivos Tricíclicos , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Técnicas de Genotipaje/métodos , Administración del Tratamiento Farmacológico/normas , Variantes Farmacogenómicas/genética , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/farmacocinética , Relación Dosis-Respuesta a Droga , Humanos , Polimorfismo Genético , Resultado del TratamientoRESUMEN
Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for codeine based on CYP2D6 genotype. This document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP2D6 genotype and codeine therapy.
Asunto(s)
Analgésicos Opioides/farmacocinética , Codeína/farmacocinética , Citocromo P-450 CYP2D6/genética , Farmacogenética , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Codeína/administración & dosificación , Codeína/efectos adversos , Citocromo P-450 CYP2D6/metabolismo , Pruebas Genéticas , Genotipo , Humanos , Morfina/metabolismo , Polimorfismo GenéticoRESUMEN
Human leukocyte antigen B (HLA-B) is a gene that encodes a cell surface protein involved in presenting antigens to the immune system. The variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in response to carbamazepine treatment. We summarize evidence from the published literature supporting this association and provide recommendations for the use of carbamazepine based on HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this article is to provide information to allow the interpretation of clinical HLA-B*15:02 genotype tests so that the results can be used to guide the use of carbamazepine. The guideline provides recommendations for the use of carbamazepine when HLA-B*15:02 genotype results are available. Detailed guidelines regarding the selection of alternative therapies, the use of phenotypic tests, when to conduct genotype testing, and cost-effectiveness analyses are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on the PharmGKB website at (http://www.pharmgkb.org).
Asunto(s)
Anticonvulsivantes/administración & dosificación , Carbamazepina/administración & dosificación , Antígenos HLA-B/genética , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/economía , Carbamazepina/efectos adversos , Carbamazepina/economía , Análisis Costo-Beneficio , Pruebas Genéticas , Variación Genética , Genotipo , Humanos , Medición de RiesgoRESUMEN
Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 polymorphisms. Codeine has little therapeutic effect in patients who are CYP2D6 poor metabolizers, whereas the risk of morphine toxicity is higher in ultrarapid metabolizers. The purpose of this guideline (periodically updated at http://www.pharmgkb.org) is to provide information relating to the interpretation of CYP2D6 genotype test results to guide the dosing of codeine.