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1.
Cleve Clin J Med ; 87(2): 91-99, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015062

RESUMO

Pharmacogenomics, ie, the study of how an individual's genomic profile influences his or her response to drugs, has emerged as a clinical tool to optimize drug therapy. Certain variants in some genes increase the risk of severe, life-threatening adverse effects from certain drugs. Integrating pharmacogenomics into clinical practice to assist in drug selection and dosing has the potential to improve the outcomes of treatment, reduce the risk of drug-induced morbidity and death, and be cost-effective.

3.
Clin Pharmacol Ther ; 107(3): 563-570, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31549389

RESUMO

A risk mitigation strategy was implemented to determine if a higher prophylactic voriconazole dosage in patients with CYP2C19 rapid metabolizer neutropenic acute myeloid leukemia (AML) reduces the incidence of subtherapeutic trough concentrations. Patients with AML (n = 263) were preemptively genotyped for CYP2C19*2, *3, and *17 alleles as part of a single-center prospective, interventional, quality improvement study. CYP2C19 rapid metabolizers (CYP2C19*1/*17) were recommended to receive interventional voriconazole 300 mg twice daily, ultrarapid metabolizers (CYP2C19*17/*17) were recommended to avoid voriconazole, and all others received the standard prophylactic dosage of 200 mg twice daily. In this real-world setting, 202 patients (76.8%) were prescribed prophylactic voriconazole, and of these patients 176 (87.1%) received CYP2C19-guided prophylactic dosing. Voriconazole trough concentrations were obtained for 41 of the 58 (70.7%) CYP2C19 rapid metabolizers prescribed prophylactic voriconazole. Interventional voriconazole resulted in higher plasma trough concentrations (median 2.7 µg/mL) compared with the standard prophylactic dosage (median 0.6 µg/mL; P = 0.001). Subtherapeutic concentrations were avoided in 83.8% of CYP2C19 rapid metabolizers receiving interventional dosage compared to 46.2% receiving standard dosage (P = 0.02). CYP2C19 genotyping to preemptively guide prophylactic voriconazole dosing is feasible and may be a potential strategy for reducing the risk of subtherapeutic trough concentrations that potentiate breakthrough fungal infections.

5.
Genet Med ; 21(10): 2255-2263, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30894703

RESUMO

PURPOSE: A number of institutions have clinically implemented CYP2D6 genotyping to guide drug prescribing. We compared implementation strategies of early adopters of CYP2D6 testing, barriers faced by both early adopters and institutions in the process of implementing CYP2D6 testing, and approaches taken to overcome these barriers. METHODS: We surveyed eight early adopters of CYP2D6 genotyping and eight institutions in the process of adoption. Data were collected on testing approaches, return of results procedures, applications of genotype results, challenges faced, and lessons learned. RESULTS: Among early adopters, CYP2D6 testing was most commonly ordered to assist with opioid and antidepressant prescribing. Key differences among programs included test ordering and genotyping approaches, result reporting, and clinical decision support. However, all sites tested for copy-number variation and nine common variants, and reported results in the medical record. Most sites provided automatic consultation and had designated personnel to assist with genotype-informed therapy recommendations. Primary challenges were related to stakeholder support, CYP2D6 gene complexity, phenotype assignment, and sustainability. CONCLUSION: There are specific challenges unique to CYP2D6 testing given the complexity of the gene and its relevance to multiple medications. Consensus lessons learned may guide those interested in pursuing similar clinical pharmacogenetic programs.

6.
Diagn Pathol ; 13(1): 77, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30314519

RESUMO

BACKGROUND: RAF family activating fusions have been described as a potentially targetable molecular finding in a subset of soft tissue sarcomas. To further expand upon the landscape of this genetic feature, we describe a novel MTAP-RAF1 activating fusion identified in a S100 positive soft tissue sarcoma. CASE PRESENTATION: A 51 year old man underwent excision of a soft tissue mass in his foot. Pathology revealed a spindle cell neoplasm with S100 positivity, ultimately classified as a soft tissue sarcoma, not otherwise specified. Comprehensive molecular profiling was performed to help establish the diagnosis and revealed a novel MTAP-RAF1 fusion that includes the tyrosine kinase domain of RAF1. CONCLUSIONS: Our report adds to the spectrum of fusion-driven RAF activation observed in soft tissue sarcomas and lends additional evidence that RAF activation plays an important role in some soft tissue sarcomas. Identification of novel fusions involving the MAPK/ERK pathway in sarcomas may provide new avenues for precision medicine strategies involving targeted kinase inhibitors.


Assuntos
Proteínas de Fusão Oncogênica/genética , Proteínas Proto-Oncogênicas c-raf/genética , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Biomarcadores Tumorais/genética , Fusão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fusão Oncogênica/genética , Proteínas Repressoras/genética , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia
7.
Clin Cancer Res ; 24(24): 6195-6203, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-30228210

RESUMO

PURPOSE: Osimertinib was initially approved for T790M-positive non-small cell lung cancer (NSCLC) and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. EXPERIMENTAL DESIGN: Using cohorts from The University of Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center lung cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients. RESULTS: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition as potential resistance drivers. Alterations of cell-cycle genes were associated with shorter median progression-free survival (PFS, 4.4 vs. 8.8 months, P = 0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second PFS (PFS2) of 12.6 months; 21 patients received local consolidation radiation with a median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared with discontinuation (11.2 vs. 6.1 months, P = 0.02). CONCLUSIONS: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib after progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients.See related commentary by Devarakonda and Govindan, p. 6112.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Mutação , Acrilamidas/administração & dosagem , Acrilamidas/efeitos adversos , Adulto , Idoso , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
9.
Contemp Clin Trials ; 68: 7-13, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29535047

RESUMO

INTRODUCTION: Pain is one of the most burdensome symptoms associated with cancer and its treatment, and opioids are the cornerstone of pain management. Opioid therapy is empirically selected, and patients often require adjustments in therapy to effectively alleviate pain or ameliorate adverse drug effects that interfere with quality of life. There are data suggesting CYP2D6 genotype may contribute to inter-patient variability in response to opioids through its effects on opioid metabolism. Therefore, we aim to determine if CYP2D6 genotype-guided opioid prescribing results in greater reductions in pain and symptom severity and interference with daily living compared to a conventional prescribing approach in patients with cancer. METHODS: Patients with solid tumors with metastasis and a self-reported pain score ≥ 4/10 are eligible for enrollment and randomized to a genotype-guided or conventional pain management strategy. For patients in the genotype-guided arm, CYP2D6 genotype information is integrated into opioid prescribing decisions. Patients are asked to complete questionnaires regarding their pain, symptoms, and quality of life at baseline and 2, 4, 6, and 8 weeks after enrollment. The primary endpoint is differential change in pain severity by treatment strategy (genotype-guided versus conventional pain management). Secondary endpoints include change in pain and symptom interference with daily living. CONCLUSION: Pharmacogenetic-guided opioid selection for cancer pain management has potential clinical utility, but current evidence is limited to retrospective and observational studies. Precision Medicine Guided Treatment for Cancer Pain is a pragmatic clinical trial that seeks to determine the utility of CYP2D6 genotype-guided opioid prescribing in patients with cancer.


Assuntos
Analgésicos Opioides/uso terapêutico , Dor do Câncer , Neoplasias/complicações , Medição da Dor/métodos , Dor do Câncer/diagnóstico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/genética , Citocromo P-450 CYP2D6/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/patologia , Manejo da Dor/métodos , Seleção de Pacientes , Farmacogenética/métodos , Ensaios Clínicos Pragmáticos como Assunto , Medicina de Precisão/métodos , Índice de Gravidade de Doença
10.
Clin Transl Sci ; 11(1): 71-76, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28749586

RESUMO

Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The percent of patients with a predicted phenotype associated with a gene-based CPIC dosing recommendation was determined. Ninety-nine patients (93.4%) elected to receive secondary pharmacogenomic findings. For each gene-drug pair analyzed, the number of patients with an actionable phenotype ranged from two (2%) to 43 patients (43.4%). Combining all gene-drug pairs, 84 unique patients (84.8%) had an actionable phenotype. A prospective multidisciplinary practice model was developed for integrating secondary pharmacogenomic findings into clinical practice. Our model highlights a unique collaboration between physician-geneticists, pharmacists, and genetic counselors.


Assuntos
Prestação Integrada de Cuidados de Saúde/métodos , Modelos Organizacionais , Equipe de Assistência ao Paciente/organização & administração , Preferência do Paciente/estatística & dados numéricos , Testes Farmacogenômicos/estatística & dados numéricos , Adulto , Tomada de Decisões , Prestação Integrada de Cuidados de Saúde/organização & administração , Feminino , Aconselhamento Genético/métodos , Aconselhamento Genético/organização & administração , Aconselhamento Genético/estatística & dados numéricos , Humanos , Comunicação Interdisciplinar , Masculino , Assistência ao Paciente/métodos , Farmacêuticos/organização & administração , Variantes Farmacogenômicos/genética , Fenótipo , Médicos/organização & administração , Estudos Prospectivos , Estudos Retrospectivos , Sequenciamento Completo do Exoma , Adulto Jovem
11.
PLoS One ; 12(9): e0185471, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28957369

RESUMO

BACKGROUND: Poor adherence to medication regimens and medical record inconsistencies result in incomplete knowledge of medication therapy in polypharmacy patients. By quantitatively identifying medications in the blood of patients and reconciling detected medications with the medical record, we have defined the severity of this knowledge gap and created a path toward optimizing medication therapy. METHODS AND FINDINGS: We validated a liquid chromatography-tandem mass spectrometry assay to detect and/or quantify 38 medications across a broad range of chronic diseases to obtain a comprehensive survey of patient adherence, medical record accuracy, and exposure variability in two patient populations. In a retrospectively tested 821-patient cohort representing U.S. adults, we found that 46% of medications assessed were detected in patients as prescribed in the medical record. Of the remaining medications, 23% were detected, but not listed in the medical record while 30% were prescribed to patients, but not detected in blood. To determine how often each detected medication fell within literature-derived reference ranges when taken as prescribed, we prospectively enrolled a cohort of 151 treatment-regimen adherent patients. In this cohort, we found that 53% of medications that were taken as prescribed, as determined using patient self-reporting, were not within the blood reference range. Of the medications not in range, 83% were below and 17% above the lower and upper range limits, respectively. Only 32% of out-of-range medications could be attributed to short oral half-lives, leaving extensive exposure variability to result from patient behavior, undefined drug interactions, genetics, and other characteristics that can affect medication exposure. CONCLUSIONS: This is the first study to assess compliance, medical record accuracy, and exposure as determinants of real-world treatment and response. Variation in medication detection and exposure is greater than previously demonstrated, illustrating the scope of current therapy issues and opening avenues that warrant further investigation to optimize medication therapy.


Assuntos
Monitoramento de Medicamentos/métodos , Registros Médicos/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos , Estudos de Coortes , Prescrições de Medicamentos , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Lung Cancer ; 111: 135-138, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28838384

RESUMO

Cell-free circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is emerging as a noninvasive technique for detecting targetable mutations. We describe two lung adenocarcinoma cases that show the clinical utility of supplementing tumor biopsy molecular interrogation with ctDNA NGS. For both cases, ctDNA NGS identified actionable mutations that were previously not reported by molecular interrogation of tissue. Explanations are provided for the observed differences between ctDNA and tumor biopsy genomic results along with considerations for reconciling findings. Case 1 consisted of a patient with multiple lesions in the left and right lung that was initially suspected to be related to malignancy. A tumor biopsy was positive for EGFR-mutated lung cancer. ctDNA NGS reported an activating KRAS mutation, which was unexpected given the rare occurrence of EGFR/KRAS co-mutations. Radiologic imaging and ctDNA NGS resulted in the diagnoses of synchronous EGFR-mutated left lung cancer and KRAS-mutated right lung cancer. The second case describes a patient who was negative for RET rearrangements by tissue interrogation, but positive for a RET-KIF5B fusion by ctDNA NGS. Further tissue analysis demonstrated heterogeneity was the cause of differing results. We demonstrate that supplementing tumor biopsies with ctDNA NGS has a crucial role in patient care. Understanding the causes of differing ctDNA and tumor biopsy genomic results is essential for reconciling findings and application to precision medicine management.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , DNA de Neoplasias , Mutação , Neoplasias/genética , Idoso , Biópsia , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Biópsia Líquida , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Medicina de Precisão/métodos , Proteínas Proto-Oncogênicas c-ret/genética
13.
Pharmacotherapy ; 37(9): 1014-1022, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28699700

RESUMO

One of the initial steps for implementing pharmacogenomics into routine patient care is selecting an appropriate clinical laboratory to perform the testing. With the rapid advances in genotyping technologies, many clinical laboratories are now performing pharmacogenomic testing. Selection of a reference laboratory depends on whether a particular genotype assay is already performed by an internal health care organization laboratory or only available externally. Other factors for consideration are coverage of genomic variants important for the patient population, technical support, and cost. In some instances, the decision to select a particular reference laboratory may be the responsibility of the clinician who is recommending genomic interrogation. Only limited guidance is available that describes the laboratory characteristics to consider when selecting a reference laboratory. We provide practical considerations for selecting a clinical laboratory for pharmacogenomic testing broadly categorized into four domains: pharmacogene and variant selection; logistics; reporting of results; and test costs along with reimbursement.


Assuntos
Ciência de Laboratório Médico/normas , Farmacogenética/normas , Medicina de Precisão/normas , Humanos , Ciência de Laboratório Médico/métodos , Farmacogenética/métodos , Medicina de Precisão/métodos , Padrões de Referência
15.
Pharmacotherapy ; 37(9): 1043-1051, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28235141

RESUMO

INTRODUCTION: Moffitt Cancer Center's Personalized Medicine Clinical Service (PMCS) reviews somatic next-generation sequencing (NGS) assay results, provides interpretations, and identifies potential therapeutic options. The number of individuals reviewed by our clinical service who are eligible for on-label or off-label drug therapy based on genetic test results has previously not been quantitated. We determined the number of patients harboring an actionable mutation that would qualify a patient for an on-label drug or consideration for off-label drug treatment. METHODS: The Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling was utilized to identify anticancer agents containing genomic markers in the Indications and Usage section of the drug label. A database containing discrete NGS patient data was queried retrospectively for those drugs and associated genomic mutations included in this study. On-label was defined as those patients who were eligible for a drug based on harboring a targetable mutation in the FDA-approved cancer type. Off-label was defined as those patients who may be considered for a drug based on harboring a targetable mutation in a non-FDA-approved cancer type. RESULTS: A total of 1072 patients and 1131 NGS results were eligible for study inclusion. Fifty-two patients (4.9%) had results for more than one NGS assay. Seventeen drugs targeting ALK, BRAF, BRCA1/BRCA2, EGFR, or ERBB2 mutations met the study inclusion criteria. Of the entire patient population, 92 (8.6%) unique patients were eligible for at least one on-label drug; off-label use of at least one drug could be considered in 103 (9.6%) unique patients. CONCLUSION: Combining both on-label and off-label opportunities, 175 (16.3%) unique patients had actionable mutations in six genes. Because most patients reviewed by our PMCS have previously treated advanced disease with limited treatment options, identifying additional lines of therapy is of clinical utility.


Assuntos
Antineoplásicos/uso terapêutico , Mutação/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Uso Off-Label , Medicina de Precisão/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Rotulagem de Medicamentos/métodos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Neoplasias/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration , Adulto Jovem
16.
Oncologist ; 22(2): 144-151, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28179575

RESUMO

BACKGROUND: The increasing practicality of genomic sequencing technology has led to its incorporation into routine clinical practice. Successful identification and targeting of driver genomic alterations that provide proliferative and survival advantages to tumor cells have led to approval and ongoing development of several targeted cancer therapies. Within many major cancer centers, molecular tumor boards are constituted to shepherd precision medicine into clinical practice. MATERIALS AND METHODS: In July 2014, the Clinical Genomics Action Committee (CGAC) was established as the molecular tumor board companion to the Personalized Medicine Clinical Service (PMCS) at Moffitt Cancer Center in Tampa, Florida. The processes and outcomes of the program were assessed in order to help others move into the practice of precision medicine. RESULTS: Through the establishment and initial 1,400 patients of the PMCS and its associated molecular tumor board at a major cancer center, five practical lessons of broad applicability have been learned: transdisciplinary engagement, the use of the molecular report as an aid to clinical management, clinical actionability, getting therapeutic options to patients, and financial considerations. Value to patients includes access to cutting-edge practice merged with individualized preferences in treatment and care. CONCLUSIONS: Genomic-driven cancer medicine is increasingly becoming a part of routine clinical practice. For successful implementation of precision cancer medicine, strategically organized molecular tumor boards are critical to provide objective evidence-based translation of observed molecular alterations into patient-centered clinical action. Molecular tumor board implementation models along with clinical and economic outcomes will define future treatment standards. The Oncologist 2017;22:144-151Implications for Practice: It is clear that the increasing practicality of genetic tumor sequencing technology has led to its incorporation as part of routine clinical practice. Subsequently, many cancer centers are seeking to develop a personalized medicine services and/or molecular tumor board to shepherd precision medicine into clinical practice. This article discusses the key lessons learned through the establishment and development of a molecular tumor board and personalized medicine clinical service. This article highlights practical issues and can serve as an important guide to other centers as they conceive and develop their own personalized medicine services and molecular tumor boards.


Assuntos
Genômica , Terapia de Alvo Molecular/métodos , Neoplasias/terapia , Medicina de Precisão/métodos , Feminino , Humanos , Masculino
17.
Am J Health Syst Pharm ; 73(23): 1967-1976, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27864204

RESUMO

PURPOSE: Existing pharmacogenomic informatics models, key implementation steps, and emerging resources to facilitate the development of pharmacogenomic clinical decision support (CDS) are described. SUMMARY: Pharmacogenomics is an important component of precision medicine. Informatics, especially CDS in the electronic health record (EHR), is a critical tool for the integration of pharmacogenomics into routine patient care. Effective integration of pharmacogenomic CDS into the EHR can address implementation challenges, including the increasing volume of pharmacogenomic clinical knowledge, the enduring nature of pharmacogenomic test results, and the complexity of interpreting results. Both passive and active CDS provide point-of-care information to clinicians that can guide the systematic use of pharmacogenomics to proactively optimize pharmacotherapy. Key considerations for a successful implementation have been identified; these include clinical workflows, identification of alert triggers, and tools to guide interpretation of results. These considerations, along with emerging resources from the Clinical Pharmacogenetics Implementation Consortium and the National Academy of Medicine, are described. CONCLUSION: The EHR with CDS is essential to curate pharmacogenomic data and disseminate patient-specific information at the point of care. As part of the successful implementation of pharmacogenomics into clinical settings, all relevant clinical recommendations pertaining to gene-drug pairs must be summarized and presented to clinicians in a manner that is seamlessly integrated into the clinical workflow of the EHR. In some situations, ancillary systems and applications outside the EHR may be integrated to augment the capabilities of the EHR.


Assuntos
Sistemas de Apoio a Decisões Clínicas/tendências , Registros Eletrônicos de Saúde/tendências , Farmacogenética/tendências , Humanos , Farmacogenética/métodos , Sistemas Automatizados de Assistência Junto ao Leito/tendências , Medicina de Precisão/métodos , Medicina de Precisão/tendências
18.
Pharmacotherapy ; 36(8): 940-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27312955

RESUMO

The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues to grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes and improve patient safety. However, pharmacogenomic implementation barriers exist such as integration of pharmacogenomic results into electronic health records (EHRs), development and deployment of pharmacogenomic decision support tools to EHRs, and feasible models for establishing ambulatory pharmacogenomic clinics. We describe the development of pharmacist-managed pharmacogenomic services within a large health system. The Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B*57:01-abacavir, HLA-B*15:02-carbamazepine, and TPMT-thiopurines (i.e., azathioprine, mercaptopurine, and thioguanine) were systematically integrated into patient care. Sixty-three custom rules and alerts (20 for TPMT-thiopurines, 8 for HLA-B*57:01-abacavir, and 35 for HLA-B*15:02-anticonvulsants) were developed and deployed to the EHR for the purpose of providing point-of-care pharmacogenomic decision support. In addition, a pharmacist and physician-geneticist collaboration established a pharmacogenomics ambulatory clinic. This clinic provides genetic testing when warranted, result interpretation along with pharmacotherapy recommendations, and patient education. Our processes for developing these pharmacogenomic services and solutions for addressing implementation barriers are presented.


Assuntos
Sistemas de Apoio a Decisões Clínicas , Registros Eletrônicos de Saúde , Farmacogenética , Encaminhamento e Consulta , Humanos
19.
Pharmacogenomics ; 17(7): 663-7, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27143031

RESUMO

Individuals who carry the CYP2C19*17 gain-of-function allele have lower voriconazole exposure and are therefore at risk of failing therapy. Utilizing CYP2C19 genotype to optimize voriconazole dosage may be a cost-effective method of improving treatment outcomes. However, there are limited data describing what initial voriconazole dosage should be used in those with increased CYP2C19 metabolic capacity. Herein, we present a case report of a pediatric CYP2C19 rapid metabolizer (i.e., CYP2C19*1/*17) requiring a voriconazole dosage of 14 mg/kg twice daily (usual pediatric dosage ranges from 7 to 9 mg/kg twice daily). This case report supports the clinical utility of using CYP2C19 genotype to guide voriconazole dosing, and provides data for establishing an initial voriconazole dose in pediatric CYP2C19 rapid metabolizers.


Assuntos
Antifúngicos/administração & dosagem , Antifúngicos/farmacocinética , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Aspergilose Pulmonar Invasiva/metabolismo , Voriconazol/administração & dosagem , Voriconazol/farmacocinética , Criança , Monitoramento de Medicamentos , Feminino , Humanos , Hospedeiro Imunocomprometido , Aspergilose Pulmonar Invasiva/cirurgia , Variantes Farmacogenômicos , Medicina de Precisão , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
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