Simvastatin is among the most commonly used prescription medications for cholesterol reduction. A single coding SNP, 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 document is an update to the 2012 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for SLCO1B1 and simvastatin-induced myopathy.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) publishes genotype-based drug guidelines to help clinicians understand how available genetic test results could be used to optimize drug therapy. CPIC has focused initially on well-known examples of pharmacogenomic associations that have been implemented in selected clinical settings, publishing nine to date. Each CPIC guideline adheres to a standardized format and includes a standard system for grading levels of evidence linking genotypes to phenotypes and assigning a level of strength to each prescribing recommendation. CPIC guidelines contain the necessary information to help clinicians translate patient-specific diplotypes for each gene into clinical phenotypes or drug dosing groups. This paper reviews the development process of the CPIC guidelines and compares this process to the Institute of Medicine’s Standards for Developing Trustworthy Clinical Practice Guidelines.

Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non-synonymous coding single-nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly.

A multidisciplinary clinic providing genotyping and related services can facilitate the integration of pharmacogenomics into clinical care and meet the needs of early adopters of precision medicine.

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.The purpose of this guideline is to provide information regarding the clinical use of IFNL3 (IL28B) genotyping to guide the use of pegylated interferon-α (PEG-IFN-α or PEG-IFN 2a and 2b) and ribavirin (RBV) combination therapy, including treatment with direct-acting antivirals approved for hepatitis C virus (HCV) genotype 1 infection. Demographic and other clinical variables, such as adherence to psychological or pharmacological therapy, concomitant use of other drugs that may influence efficacy of antiviral treatment, or patient-specific disease characteristics, are not the focus of this guideline. The Clinical Pharmacogenetics Implementation Consortium develops peer-reviewed guidelines that are published and updated regularly at http://www.pharmgkb.org on the basis of emerging evidence. FOCUSED LITERATURE REVIEWA systematic literature review focused on IFNL3 (IL28B) genotype and PEG-IFN-α use was conducted (see Supplementary Material online). This guideline was developed on the basis of interpretation of the literature by the authors and experts in the field. DRUGS: PEG-IFN-α BackgroundInfection with HCV affects >150 million people worldwide and is one of the leading causes of cirrhosis and hepatocellular carcinoma (hepatitis C fact sheet, Geneva, Switzerland: World Health Organization; accessed 30 September 2012 at http://www.who. int/mediacentre/factsheets/fs164/en/index.html). Before 2011, treatment for chronic HCV infection consisted of combination PEG-IFN-α and RBV therapy for 24 weeks for HCV genotypes 2 and 3 and for 48 weeks for other HCV genotypes. 1 In 2011, two first-generation HCV protease inhibitors, boceprevir and telaprevir, were approved to treat HCV genotype 1 infection in many countries, including the United States and the countries of the European Union. These direct-acting antiviral agents are indicated in combination with PEG-IFN-α and RBV therapy for patients with HCV genotype 1 infection, and this regimen is preferred over PEG-IFN-α and RBV alone in countries where direct-acting antivirals have been approved.The primary goal of treatment is eradication of HCV as measured by sustained virologic response (SVR, defined by undetectable serum viral RNA 12-24 weeks after the end of treatment), which equates with cure of the infection and leads to lower morbidity and mortality. 2 However, combination therapy for HCV treatment has a number of limitations. The treatment is expensive, is associated with many side effects, and lasts 24-48 weeks. SVR rates are low for ...

Purpose Educational barriers hinder the widespread application of pharmacogenomics in clinical practice. This review summarizes requisite pharmacist competencies, educational standards, and the current state of pharmacogenomics education to propose best practice solutions for educators to meet the specific needs and challenges of this complex topic. Summary Consensus-based pharmacist competencies and clinical guidelines have been published to guide knowledge attainment and application of pharmacogenomics concepts. Pharmacogenomics education is often integrated into existing courses and increasingly, within required standalone courses within PharmD curricula. Continuing education programs and limited postgraduate residencies/fellowship training opportunities are available to practitioners. However, challenges in identifying the optimal structure and amount of coverage, limited number of faculty experts, and inadequate availability of advanced pharmacogenomics practice settings for experiential education are limiting. Fortunately, successful approaches are emerging for both students and practitioners. In pharmacy schools, strategies include early exposure through foundational courses, incorporation into practice-based therapeutics courses, and introductory and advanced pharmacy practice experiences. For practitioners, institution-specific training, online resources, education within clinical decision support tools, and certificate programs can supplement more robust structured post-graduate training programs. Recent data also show the success of shared curricula and participatory education models involving an opportunity for learners to undergo personal genomic testing first-hand. Conclusion The pharmacy profession has taken a leadership role in expanding student and practitioner education to meet the demands of precision medicine initiatives. Effective approaches to attain pharmacogenomics knowledge and to drive its appropriate application in clinical practice are increasingly available.

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By assertively advancing ambulatory care practice, pharmacy will help achieve the national priorities of improving patient care, patient health, and affordability of care.