RESUMEN
Both the Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group provide therapeutic recommendations for well-known gene-drug pairs. Published recommendations show a high rate of concordance. However, as a result of different guideline development methods used by these two consortia, differences between the published guidelines exist. The aim of this paper is to compare both initiatives and explore these differences, with the objective to achieve harmonization.
Asunto(s)
Farmacogenética , Guías de Práctica Clínica como Asunto , Medicina de Precisión , Pruebas Genéticas/métodos , Humanos , Países Bajos , Farmacogenética/métodos , Farmacogenética/normas , Pautas de la Práctica en Medicina , Medicina de Precisión/métodos , Medicina de Precisión/normas , Investigación Biomédica Traslacional/métodos , Investigación Biomédica Traslacional/normas , Estados UnidosRESUMEN
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
Asunto(s)
Anticoagulantes/administración & dosificación , Citocromo P-450 CYP2C9/genética , Familia 4 del Citocromo P450/genética , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Adulto , Niño , Relación Dosis-Respuesta a Droga , Genotipo , Humanos , Farmacogenética , Guías de Práctica Clínica como AsuntoAsunto(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 TratamientoAsunto(s)
Citocromo P-450 CYP2D6/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Pruebas Genéticas/métodos , Ondansetrón/farmacología , Náusea y Vómito Posoperatorios/prevención & control , Tropisetrón/farmacología , Antieméticos/farmacología , Humanos , Farmacogenética/métodos , Polimorfismo Genético , Radioterapia/efectos adversos , Agonistas del Receptor de Serotonina 5-HT3/farmacologíaRESUMEN
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
Asunto(s)
Citocromo P-450 CYP2C19/genética , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Técnicas de Genotipaje/métodos , Tasa de Depuración Metabólica/fisiología , Voriconazol , Antifúngicos/farmacocinética , Antifúngicos/uso terapéutico , Relación Dosis-Respuesta a Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/prevención & control , Humanos , Selección de Paciente , Variantes Farmacogenómicas/genética , Medición de Riesgo/métodos , Voriconazol/farmacocinética , Voriconazol/uso terapéuticoRESUMEN
The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplemental Material and included additional resources for applying CPIC guidelines into the electronic health record. Up-to-date information can be found at PharmGKB (http://www.pharmgkb.org).
Asunto(s)
Alopurinol/administración & dosificación , Biomarcadores Farmacológicos , Guías como Asunto/normas , Antígenos HLA-B/genética , Esquema de Medicación , Genotipo , HumanosRESUMEN
The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).
Asunto(s)
Sulfato de Atazanavir/efectos adversos , Glucuronosiltransferasa/antagonistas & inhibidores , Inhibidores de la Proteasa del VIH/efectos adversos , Hiperbilirrubinemia/inducido químicamente , Ictericia/inducido químicamente , Hígado/efectos de los fármacos , Farmacogenética/normas , Predisposición Genética a la Enfermedad , Genotipo , Glucuronosiltransferasa/genética , Glucuronosiltransferasa/metabolismo , Humanos , Hiperbilirrubinemia/enzimología , Hiperbilirrubinemia/genética , Ictericia/enzimología , Ictericia/genética , Hígado/enzimología , Fenotipo , Medición de Riesgo , Factores de RiesgoRESUMEN
This article provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward.
Asunto(s)
Alelos , Pruebas Genéticas/normas , Farmacogenética/normas , Terminología como Asunto , Genes , Pruebas Genéticas/tendencias , Variación Genética , Humanos , Farmacogenética/tendencias , Medicina de PrecisiónRESUMEN
Selective serotonin reuptake inhibitors (SSRIs) are primary treatment options for major depressive and anxiety disorders. CYP2D6 and CYP2C19 polymorphisms can influence the metabolism of SSRIs, thereby affecting drug efficacy and safety. We summarize evidence from the published literature supporting these associations and provide dosing recommendations for fluvoxamine, paroxetine, citalopram, escitalopram, and sertraline based on CYP2D6 and/or CYP2C19 genotype (updates at www.pharmgkb.org).
Asunto(s)
Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2D6/genética , Cálculo de Dosificación de Drogas , Farmacogenética/normas , Polimorfismo Genético , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Biotransformación , Citocromo P-450 CYP2C19/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Genotipo , Humanos , Seguridad del Paciente , Fenotipo , Medición de Riesgo , Factores de Riesgo , Inhibidores Selectivos de la Recaptación de Serotonina/efectos adversos , Inhibidores Selectivos de la Recaptación de Serotonina/farmacocinéticaRESUMEN
Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared with those who are CYP3A5 nonexpressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).
Asunto(s)
Citocromo P-450 CYP3A/genética , Inmunosupresores/administración & dosificación , Tacrolimus/administración & dosificación , Pruebas Genéticas , Genotipo , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de ÓrganosRESUMEN
Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin. Detailed guidelines for the use of phenytoin as well as analyses of cost-effectiveness are out of scope. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are periodically updated at http://www.pharmgkb.org.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Citocromo P-450 CYP2C9/genética , Antígenos HLA-B/genética , Fenitoína/administración & dosificación , Genotipo , Humanos , Farmacogenética , Fenotipo , Fenitoína/efectos adversosRESUMEN
Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding single-nucleotide polymorphism, rs4149056T>C, in SLCO1B1 increases systemic exposure to simvastatin and the risk of muscle toxicity. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for simvastatin based on SLCO1B1 genotype. This article is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Musculares/inducido químicamente , Transportadores de Anión Orgánico/genética , Simvastatina/uso terapéutico , Interacciones Farmacológicas , Genotipo , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacocinética , Transportador 1 de Anión Orgánico Específico del Hígado , Farmacogenética , Polimorfismo Genético , Simvastatina/efectos adversos , Simvastatina/farmacocinéticaRESUMEN
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia (AHA) induced by a number of drugs. We provide guidance as to which G6PD genotypes are associated with G6PD deficiency in males and females. Rasburicase is contraindicated in G6PD-deficient patients due to the risk of AHA and possibly methemoglobinemia. Unless preemptive genotyping has established a positive diagnosis of G6PD deficiency, quantitative enzyme assay remains the mainstay of screening prior to rasburicase use. The purpose of this article is to help interpret the results of clinical G6PD genotype tests so that they can guide the use of rasburicase. Detailed guidelines on other aspects of the use of rasburicase, including analyses of cost-effectiveness, are beyond the scope of this document. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are published and updated periodically on https://www.pharmgkb.org/page/cpic to reflect new developments in the field.
Asunto(s)
Genotipo , Deficiencia de Glucosafosfato Deshidrogenasa/tratamiento farmacológico , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Farmacogenética/normas , Urato Oxidasa/uso terapéutico , Animales , Deficiencia de Glucosafosfato Deshidrogenasa/enzimología , Humanos , Farmacogenética/tendenciasRESUMEN
Cystic fibrosis (CF) is a life-shortening disease arising as a consequence of mutations within the CFTR gene. Novel therapeutics for CF are emerging that target CF transmembrane conductance regulator protein (CFTR) defects resulting from specific CFTR variants. Ivacaftor is a drug that potentiates CFTR gating function and is specifically indicated for CF patients with a particular CFTR variant, G551D-CFTR (rs75527207). Here, we provide therapeutic recommendations for ivacaftor based on preemptive CFTR genotype results.
Asunto(s)
Aminofenoles/uso terapéutico , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/tratamiento farmacológico , Farmacogenética , Quinolonas/uso terapéutico , Pruebas Genéticas , 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 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
Pegylated interferon-α (PEG-IFN-α or PEG-IFN 2a and 2b)- and ribavirin (RBV)-based regimens are the mainstay for treatment of hepatitis C virus (HCV) genotype 1. IFNL3 (IL28B) genotype is the strongest baseline predictor of response to PEG-IFN-α and RBV therapy in previously untreated patients and can be used by patients and clinicians as part of the shared decision-making process for initiating treatment for HCV infection. We provide information regarding the clinical use of PEG-IFN-α- and RBV-containing regimens based on IFNL3 genotype.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interleucinas/genética , Polietilenglicoles/uso terapéutico , Antivirales/administración & dosificación , Quimioterapia Combinada , Pruebas Genéticas/normas , Genotipo , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferones , Polietilenglicoles/administración & dosificación , Polimorfismo de Nucleótido Simple/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Ribavirina/administración & dosificación , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
The fluoropyrimidines are the mainstay chemotherapeutic agents for the treatment of many types of cancers. Detoxifying metabolism of fluoropyrimidines requires dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene), and reduced or absent activity of this enzyme can result in severe, and sometimes fatal, toxicity. We summarize evidence from the published literature supporting this association and provide dosing recommendations for fluoropyrimidines based on DPYD genotype (updates at http://www.pharmgkb.org).
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Dihidrouracilo Deshidrogenasa (NADP)/genética , Fluorouracilo/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Deficiencia de Dihidropirimidina Deshidrogenasa/diagnóstico , Deficiencia de Dihidropirimidina Deshidrogenasa/genética , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Genotipo , Humanos , Hallazgos Incidentales , Masculino , Medición de Riesgo , Factores Sexuales , Tegafur/administración & dosificación , Tegafur/efectos adversosRESUMEN
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).
