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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 ). [ABSTRACT FROM AUTHOR]

The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15-1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended., (© 2023 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aim: To assess knowledge, confidence and perceptions of healthcare professionals specializing in primary care and pain management at Brigham and Women's Hospital, related to clinical pharmacogenomics (PGx). Methods: A 25-question online survey was distributed to 328 Brigham and Women's Hospital clinicians for analysis. Results: Thirty-four clinicians completed the survey. Respondents had minimal experience with PGx and limited awareness of PGx resources. Although respondents expressed belief that PGx has utility to improve medication-related patient outcomes, many lack confidence to apply PGx results to their practice. For clinical drug-gene questions relevant to primary care and/or pain management, respondents scored poorly. Conclusion: More clinician education is needed for appropriate utilization of PGx in clinical practice as it pertains to primary care and pain management.

As genomic medicine becomes increasingly complex, pharmacists need to work collaboratively with other healthcare professionals to provide genomics-based care. The core pharmacist competencies in genomics were recently updated and mapped to the entrustable professional activities (EPAs). The new competency that is mapped to the "Interprofessional Team Member" EPA domain emphasizes the role of pharmacists as the pharmacogenomics experts in an interprofessional healthcare team. Interprofessional education (IPE) activities involving student pharmacists and students from other healthcare disciplines are crucial to prepare student pharmacists for a team-based approach to patient-centered care. This commentary discusses the pharmacogenomics-focused IPE activities implemented by 3 programs, the challenges faced, and the lessons learned. It also discusses strategies to develop pharmacogenomics-focused IPE activities based on existing resources. Developing pharmacogenomics-focused IPE activities will help prepare pharmacy graduates with the knowledge, skills, and attitudes to lead collaborative, interprofessional teams in the provision of pharmacogenomics-based care, consistent with the standards described in the genomics competencies for pharmacists., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 American Association of Colleges of Pharmacy. All rights reserved.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with development of acute hemolytic anemia in the setting of oxidative stress, which can be caused by medication exposure. Regulatory agencies worldwide warn against the use of certain medications in persons with G6PD deficiency, but in many cases, this information is conflicting, and the clinical evidence is sparse. This guideline provides information on using G6PD genotype as part of the diagnosis of G6PD deficiency and classifies medications that have been previously implicated as unsafe in individuals with G6PD deficiency by one or more sources. We classify these medications as high, medium, or low to no risk based on a systematic review of the published evidence of the gene-drug associations and regulatory warnings. In patients with G6PD deficiency, high-risk medications should be avoided, medium-risk medications should be used with caution, and low-to-no risk medications can be used with standard precautions, without regard to G6PD phenotype. This new document replaces the prior Clinical Pharmacogenetics Implementation Consortium guideline for rasburicase therapy in the context of G6PD genotype (updates at: www.cpicpgx.org)., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

CYP2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 genotype impacts clopidogrel active metabolite formation. CYP2C19 intermediate and poor metabolizers who receive clopidogrel experience reduced platelet inhibition and increased risk for major adverse cardiovascular and cerebrovascular events. This guideline is an update to the 2013 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of clopidogrel based on CYP2C19 genotype and includes expanded indications for CYP2C19 genotype-guided antiplatelet therapy, increased strength of recommendation for CYP2C19 intermediate metabolizers, updated CYP2C19 genotype to phenotype translation, and evidence from an expanded literature review (updates at www.cpicpgx.org)., (© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)

Purpose: This article explores approaches to pharmacogenomic counseling for patients who have undergone multigene panel testing by describing the collective experience of 5 institutions., Summary: Multigene panel pharmacogenomic testing has the potential to unlock a myriad of information about a patient's past, present, and future drug response. The multifaceted nature of drug response coupled with the complexity of genetic results necessitates some form of patient education through pharmacogenomic counseling. Published literature regarding disclosure of pharmacogenomic test results is limited. This article compares the counseling practices of pharmacists from 5 different institutions with pharmacogenomics clinics whose experience represents perspectives ranging from academia to community clinical environments. Overarching counseling themes discussed during result disclosure center around (1) pharmacogenomic results, (2) gene-drug interactions, (3) gene-drug-drug interactions, (4) drug changes (5) future, familial, or disease-risk implications, (6) updates in the interpretation and application of pharmacogenomic results, (7) gauging patient comprehension, and (8) sharing results and supplemental information., Conclusion: Dedicating time to counseling patients on the results of a multigene pharmacogenomic panel is important given the lifelong applications of a test that is generally performed only once. The content and methods of disclosing test results shared by the experiences of pharmacists at 5 different institutions serve as guide to be further refined as research addresses effective communication strategies that enhance patient comprehension of pharmacogenomic results., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Genomics is becoming an increasingly important part of health care, and pharmacists are well-positioned to be practice-based leaders in pharmacogenomics and precision medicine. Competencies available through the Genetics/Genomics Competency Center provide a framework for pharmacogenomics instruction in both pharmacy school curricula and continuing education programs. Given the significant advancements in pharmacogenomics over the past decade, the 2019-2020 American Association of Colleges of Pharmacy Pharmacogenomics Special Interest Group updated the pharmacist competencies. The process used a systematic approach which included mapping pharmacogenomics-specific competencies to the entrustable professional activities for pharmacists and seeking consensus from key stakeholders. The result is an expansion to 30 competencies that reflect the contemporary roles pharmacists play in the application of pharmacogenomics in clinical practice. When implemented into curricula, these competencies will ensure that learners are "practice ready" to integrate pharmacogenomics into patient care. Additional postgraduate training is needed for advanced roles in pharmacogenomics implementation, education, and research., (© 2022 American Association of Colleges of Pharmacy.)

Ineffective pain control is the most commonly cited reason for misuse of prescription opioids and is influenced by genetics. In particular, the gene encoding the CYP2D6 enzyme, which metabolizes some of the most commonly prescribed opioids (e.g., tramadol, hydrocodone) to their more potent forms, is highly polymorphic and can lead to reduced concentrations of the active metabolites and decreased opioid effectiveness. Consideration of the CYP2D6 genotype may allow for predicting opioid response and identifying patients who are likely to respond well to lower potency opioids as well as those who may derive greater pain relief from non-opioid analgesics versus certain opioids. There is emerging evidence that a CYP2D6 -guided approach to pain management improves pain control and reduces opioid consumption and thus may be a promising means for combating opioid misuse. Clinical practice guidelines are available for select opioids and other analgesics to support medication and dose selection based on pharmacogenetic data. This article describes the evidence supporting genotype-guided pain management as a means of improving pain control and reducing opioid misuse and clinical recommendations for genotype-guided analgesic prescribing. In addition, a "how to" guide using patient case examples is provided to demystify the process for implementing pharmacogenetics-guided pain management in order to optimize analgesia and minimize adverse effects. Optimizing pain management through genotype-guided approaches may ultimately provide safer and more effective therapy for pain control while decreasing the risk for opioid misuse., Competing Interests: Conflict of interest: DM Smith reports grants (to institution) from Kailos Genetics

With increasing patient interest in and access to pharmacogenomic testing, clinicians practicing in primary care are more likely than ever to encounter a patient seeking or presenting with pharmacogenomic test results. Gene-based prescribing recommendations are available to healthcare providers through Food and Drug Administration-approved drug labeling and Clinical Pharmacogenetics Implementation Consortium guidelines. Given the lifelong utility of pharmacogenomic test results to optimize pharmacotherapy for commonly prescribed medications, appropriate documentation of these results in a patient's electronic health record (EHR) is essential. The current "gold standard" for pharmacogenomics implementation includes entering pharmacogenomic test results into EHRs as discrete results with associated clinical decision support (CDS) alerts that will fire at the point of prescribing, similar to drug allergy alerts. However, such infrastructure is limited to the few institutions that have invested in the resources and personnel to develop and maintain it. For the majority of clinicians who do not practice at an institution with a dedicated clinical pharmacogenomics team and integrated pharmacogenomics CDS in the EHR, this report provides practical tips for documenting pharmacogenomic test results in the problem list and allergy field to maximize the visibility and utility of results over time, especially when such results could prevent the occurrence of serious adverse drug reactions or predict therapeutic failure.

Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations., (© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Medication-related harm represents a significant issue for patient safety and quality of care. One strategy to avoid preventable adverse drug events is to utilize patient-specific factors such as pharmacogenomics (PGx) to individualize therapy., Objective: We measured the number of patients enrolled in a health-system biobank with actionable PGx results who received relevant medications and assessed the incidence of adverse drug events (ADEs) that might have been prevented had the PGx results been used to inform prescribing., Methods: Patients with actionable PGx results in the following four genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines were identified: HLA-A*31:01, HLA-B*15:02, TPMT, and VKORC1. The patients who received interacting medications (carbamazepine, oxcarbazepine, thiopurines, or warfarin) were identified, and electronic health records were reviewed to determine the incidence of potentially preventable ADEs., Results: Of 36,424 patients with PGx results, 2327 (6.4%) were HLA-A*31:01 positive; 3543 (9.7%) were HLA-B*15:02 positive; 2893 (7.9%) were TPMT intermediate metabolizers; and 4249 (11.7%) were homozygous for the VKORC1 c.1639 G>A variant. Among patients positive for one of the HLA variants who received carbamazepine or oxcarbazepine (n = 92), four (4.3%) experienced a rash that warranted drug discontinuation. Among the TPMT intermediate metabolizers who received a thiopurine (n = 56), 11 (19.6%) experienced severe myelosuppression that warranted drug discontinuation. Among patients homozygous for the VKORC1 c.1639 G>A variant who received warfarin (n = 379), 85 (22.4%) experienced active bleeding and/or international normalized ratio (INR) > 5 that warranted drug discontinuation or dose reduction., Conclusion: Patients with actionable PGx results from a health-system biobank who received relevant medications experienced predictable ADEs. These ADEs may have been prevented if the patients' PGx results were available in the electronic health record with clinical decision support prior to prescribing.

Objective. To characterize advanced pharmacy practice experiences (APPEs) with a primary focus in pharmacogenomics at schools and colleges of pharmacy in the United States. Methods. This was a cross-sectional, multicenter, observational study of pharmacogenomics APPEs at US pharmacy schools. Directors of experiential education at 146 accredited schools of pharmacy were contacted by phone and asked if their school offered a pharmacogenomics APPE. The preceptors of pharmacogenomics APPEs identified by this phone screen were sent an email with a link to an online survey that asked about their APPE offerings. Results. Of the 142 schools of pharmacy that were successfully reached via phone, 40 (28%) offered an APPE with a primary focus in pharmacogenomics. Thirty unique APPEs with pharmacogenomics as a primary focus were identified. The total number of preceptors involved in the pharmacogenomics APPEs was 33: 19 (58%) faculty preceptors and 14 (42%) non-faculty preceptors. Twenty-three of the 30 pharmacogenomics APPEs completed the survey (77% response rate). The APPE sites were diverse and included academic medical centers, community health systems, pharmacogenomic testing laboratories, and schools of pharmacy. Each pharmacogenomics APPE accommodated an average of six students per year. The APPE activities varied across sites. Conclusion. Only a small number of US pharmacy schools offer an APPE with a primary focus in pharmacogenomics. These rotations are diverse in scope and precepted by faculty or non-faculty pharmacists. The Academy should pursue opportunities to increase experiential education in pharmacogenomics., (© 2020 American Association of Colleges of Pharmacy.)

In 2009, the Clinical Pharmacogenetics Implementation Consortium (CPIC, www.cpicpgx.org), a shared project between Pharmacogenomics Knowledge Base (PharmGKB, http://www.pharmgkb.org) and the National Institutes of Health (NIH), was created to provide freely available, evidence-based, peer-reviewed, and updated pharmacogenetic clinical practice guidelines. To date, CPIC has published 23 guidelines (of which 11 have been updated), covering 19 genes and 46 drugs across several therapeutic areas. CPIC also now provides additional resources to facilitate the implementation of pharmacogenetics into routine clinical practice and the electronic health record. Furthermore, since its inception, CPIC's interactions with other resources, databases, websites, and genomic communities have grown. The purpose of this paper is to highlight the progress of CPIC over the past 10 years., (© 2019 The Authors Clinical Pharmacology & Therapeutics © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Translating CYP2D6 genotype to metabolizer phenotype is not standardized across clinical laboratories offering pharmacogenetic (PGx) testing and PGx clinical practice guidelines, such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG). The genotype to phenotype translation discordance between laboratories and guidelines can cause discordant cytochrome P450 2D6 (CYP2D6) phenotype assignments and, thus lead to inconsistent therapeutic recommendations and confusion among patients and clinicians. A modified-Delphi method was used to obtain consensus for a uniform system for translating CYP2D6 genotype to phenotype among a panel of international CYP2D6 experts. Experts with diverse involvement in CYP2D6 interpretation (clinicians, researchers, genetic testing laboratorians, and PGx implementers; n = 37) participated in conference calls and surveys. After completion of 7 surveys, a consensus (> 70%) was reached with 82% of the CYP2D6 experts agreeing to the final CYP2D6 genotype to phenotype translation method. Broad adoption of the proposed CYP2D6 genotype to phenotype translation method by guideline developers, such as CPIC and DPWG, and clinical laboratories as well as researchers will result in more consistent interpretation of CYP2D6 genotype., (© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

The HIV type-1 nonnucleoside reverse transcriptase inhibitor, efavirenz, is widely used to treat HIV type-1 infection. Efavirenz is predominantly metabolized into inactive metabolites by cytochrome P450 (CYP)2B6, and patients with certain CYP2B6 genetic variants may be at increased risk for adverse effects, particularly central nervous system toxicity and treatment discontinuation. We summarize the evidence from the literature and provide therapeutic recommendations for efavirenz prescribing based on CYP2B6 genotypes., (© 2019 The Authors Clinical Pharmacology & Therapeutics  © 2019 American Society for Clinical Pharmacology and Therapeutics.)

Objective: To explore the implications of direct-to-consumer pharmacogenomic testing for community pharmacy practice., Summary: In October 2018, the U.S. Food and Drug Administration provided approval for direct-to-consumer genetic testing company, 23andMe (Mountain View, CA), to return select pharmacogenomic test results to their customers. Given the community pharmacist's high accessibility to the public and in-depth knowledge of pharmacology, and the availability of direct-to-consumer genetic testing kits at pharmacies, it is likely that patients will present their pharmacogenomic test results to their pharmacists and expect them to incorporate those results into their care. It is important, therefore, that community pharmacists are aware of the clinical implications of these results, know where to turn for evidence-based clinical pharmacogenomics information, and be mindful of the need for confirmatory testing before changing therapy., Conclusion: Community pharmacists are at the frontlines of health care, and as such will be at the frontlines of direct-to-consumer pharmacogenomic testing. In the near future, it is likely that community pharmacists will need to counsel patients on the interpretation and appropriate use of direct-to-consumer pharmacogenomic test results., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Precision pharmacotherapy encompasses the use of therapeutic drug monitoring; evaluation of liver and renal function, genomics, and environmental and lifestyle exposures; and analysis of other unique patient or disease characteristics to guide drug selection and dosing. This paper articulates real-world clinical applications of precision pharmacotherapy, focusing exclusively on the emerging field of clinical pharmacogenomics. This field is evolving rapidly, and clinical pharmacists now play an invaluable role in the clinical implementation, education, and research applications of pharmacogenomics. This paper provides an overview of the evolution of pharmacogenomics in clinical pharmacy practice, together with recommendations on how the American College of Clinical Pharmacy (ACCP) can support the advancement of clinical pharmacogenomics implementation, education, and research. Commonalities among successful clinical pharmacogenomics implementation and education programs are identified, with recommendations for how ACCP can leverage and advance these common themes. Opportunities are also provided to support the research needed to move the practice and application of pharmacogenomics forward.

Objective: This study evaluates pediatric ambulatory care training opportunities for postgraduate year 2 (PGY2) pediatric pharmacy residents., Methods: An online survey was disseminated to PGY2 pediatric pharmacy residency directors. The questions involved the number and type of pediatric ambulatory care rotations offered; number of preceptors who practice in pediatric ambulatory care; whether or not a pediatric ambulatory care rotation is a requirement of the program; length and format of the rotations; amount of time residents spend in the pediatric ambulatory care setting; and the resident's role during pediatric ambulatory care rotations., Results: The survey yielded an 85% response rate (n = 41/48). Most residency programs offer at least 1 pediatric ambulatory care rotation (n = 38; 93%), most of which are longitudinal experiences, and two thirds of programs require their resident(s) to complete a pediatric ambulatory care rotation (n = 27; 66%). These experiences involve a variety of specialty clinics, and residents assume diverse roles and responsibilities. Few programs offer residents the opportunity to practice under a collaborative drug therapy management agreement (n = 6; 15%) or develop new clinical services (n = 6; 15%). Most residency program directors (n = 39; 95%) reported that less than 25% of their residency graduates work in the pediatric ambulatory care setting., Conclusions: Ambulatory care experiences in PGY2 pediatric pharmacy residency programs are diverse in number and scope. There is an opportunity to expand pediatric ambulatory care rotation offerings, particularly with respect to collaborative drug therapy management and the establishment of new clinical services.

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., (© 2017 American Society for Clinical Pharmacology and Therapeutics.)

The variant allele HLA-B*15:02 is strongly associated with greater risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients treated with carbamazepine or oxcarbazepine. The variant allele HLA-A*31:01 is associated with greater risk of maculopapular exanthema, drug reaction with eosinophilia and systemic symptoms, and SJS/TEN in patients treated with carbamazepine. We summarize evidence from the published literature supporting these associations and provide recommendations for carbamazepine and oxcarbazepine use based on HLA genotypes., (© 2018 American Society for Clinical Pharmacology and Therapeutics.)

Purpose: The structure and development of an innovative, ASHP-accredited postgraduate year 2 (PGY2) clinical pharmacogenetics residency program are described., Summary: A 12-month PGY2 clinical pharmacogenetics residency was created at St. Jude Children's Research Hospital in accordance with the ASHP standards for advanced practice residencies. The purpose of this 12-month residency program is to prepare pharmacy residents to implement pharmacogenetics in clinical practice. The program helps residents develop expertise in the science of pharmacogenetics as well as an understanding of translational research, innovative pharmacy practice model development, and clinical informatics. The resident learns to optimize patient outcomes through the expert provision of evidence-based, patient-centered precision medicine as an integral part of an interprofessional team. After completing the program, residents are expected to have the clinical skills necessary to practice in the field of clinical pharmacogenetics and independently implement pharmacogenetic testing in other health-system settings. Because implementation of pharmacogenetics requires collaboration across many disciplines, residents works within an interprofessional team of physicians, nurses, informatics specialists, pharmacists, and clinical laboratory personnel to achieve program goals. Since the first resident graduated in 2012, the program has graduated 1 resident each year. Graduated residents have accepted pharmacogenetics positions at major academic medical centers and community hospitals, as well as academic and research positions with a pharmacogenetics emphasis., Conclusion: A PGY2 clinical pharmacogenetics residency was successfully developed at St. Jude in 2013. After completion of the program, residents are equipped with the clinical skills and necessary experience to drive precision medicine forward and lead the implementation of pharmacogenetic testing in other healthcare settings., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: The current state of pharmacogenetic data curation and dissemination is described, and evidence-based resources for applying pharmacogenetic data in clinical practice are reviewed., Summary: Implementation of pharmacogenetics in clinical practice has been relatively slow despite substantial scientific progress in understanding linkages between genetic variation and variability of drug response and effect. One factor that has inhibited the adoption of genetic data to guide medication use is a lack of knowledge of how to translate genetic test results into clinical action based on currently available evidence. Other implementation challenges include controversy over selection of appropriate evidentiary thresholds for routine clinical implementation of pharmacogenetic data and the difficulty of compiling scientific data to support clinical recommendations given that large randomized controlled trials to demonstrate the utility of pharmacogenetic testing are not feasible or are not considered necessary to establish clinical utility. Organizations such as the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Pharmacogenomics Knowledgebase (PharmGKB) systematically evaluate emerging evidence of pharmacogenomic linkages and publish evidence-based prescribing recommendations to inform clinical practice. Both CPIC and PharmGKB provide online resources that facilitate the interpretation of genetic test results and provide prescribing recommendations for specific gene-drug pairs., Conclusion: Resources provided by organizations such as CPIC and PharmGKB, which use standardized approaches to evaluate the literature and provide clinical guidance for a growing number of gene-drug pairs, are essential for the implementation of pharmacogenetics into routine clinical practice., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

After postoperative deaths in children who were prescribed codeine, several pediatric hospitals have removed it from their formularies. These deaths were attributed to atypical cytochrome P450 2D6 (CYP2D6) pharmacogenetics, which is also implicated in poor analgesic response. Because codeine is often prescribed to patients with sickle cell disease and is now the only Schedule III opioid analgesic in the United States, we implemented a precision medicine approach to safely maintain codeine as an option for pain control. Here we describe the implementation of pharmacogenetics-based codeine prescribing that accounts for CYP2D6 metabolizer status. Clinical decision support was implemented within the electronic health record to guide prescribing of codeine with the goal of preventing its use after tonsillectomy or adenoidectomy and in CYP2D6 ultra-rapid and poor metabolizer (high-risk) genotypes. As of June 2015, CYP2D6 genotype results had been reported for 2468 unique patients. Of the 830 patients with sickle cell disease, 621 (75%) had a CYP2D6 genotype result; 7.1% were ultra-rapid or possible ultra-rapid metabolizers, and 1.4% were poor metabolizers. Interruptive alerts recommended against codeine for patients with high-risk CYP2D6 status. None of the patients with an ultra-rapid or poor metabolizer genotype were prescribed codeine. Using genetics to tailor analgesic prescribing retained an important therapeutic option by limiting codeine use to patients who could safely receive and benefit from it. Our efforts represent an evidence-based, innovative medication safety strategy to prevent adverse drug events, which is a model for the use of pharmacogenetics to optimize drug therapy in specialized pediatric populations., (Copyright © 2016 by the American Academy of Pediatrics.)

Purpose: The first published report of the use of triple therapy in a patient with hepatitis C virus (HCV) genotype 6 infection-a treatment that was prescribed due to incorrect HCV genotyping and which ultimately failed-is presented., Summary: A 70-year-old male U.S. resident of Vietnamese descent requested treatment for chronic HCV infection acquired decades earlier. He reported experiencing hepatitis C treatment failures twice before-13 years prior (interferon alfa monotherapy for six months) and 7 years prior (standard dual therapy with pegylated interferon alfa-2b and ribavirin for nine months). Initial viral genotyping indicated infection with HCV genotypes 1a and 6c (a form of mixed HCV disease amenable to triple therapy), and treatment with pegylated interferon alfa-2a, ribavirin, and boceprevir was initiated. By week 8 of triple therapy, the patient's viral load had decreased from 15,700,000 (7.20 log) to 462,882 (5.67 log) IU/mL, but the viral load subsequently rebounded to baseline levels, and treatment was discontinued at week 16. When repeat HCV genotyping was performed, it was discovered that initial genotyping was incorrect and that the man's infection involved not mixed genotypes but only genotype 6; he was not an appropriate candidate for triple therapy. The case emphasizes the need for clinicians to be cognizant of potential HCV genotyping errors, particularly with regard to patients of Southeast Asian descent., Conclusion: Three courses of interferon-based treatment, including triple therapy with boceprevir, failed to produce a sustained therapeutic response in a 70-year-old ethnic Vietnamese man with genotype 6 HCV infection.