Pharmacogenomics competencies in pharmacy practice: A blueprint for change.

The emerging use of genomic data to inform medication therapy populates the medical literature and provides evidence for guidelines in the prescribing information for many medications. Despite the availability of pharmacogenomic studies, few pharmacists feel competent to use these new data in patient care. The first pharmacogenomics competency statement for pharmacists was published in 2002. In 2011, the Pharmacogenomics Special Interest Group of the American Association of Colleges of Pharmacy led a process to update this competency statement with the use of a consensus-based method that incorporated input from multiple key professional pharmacy organizations to reflect growth in genomic science as well as the need for pharmacist application of genomic data. Given the rapidly evolving science, educational needs, and practice models in this area, a standardized competency-based approach to pharmacist education and training in pharmacogenomics is needed to equip pharmacists for leadership roles as essential members of health care teams that implement clinical utilization strategies for genomic data.

Implementation of a pharmacogenomics service in a community pharmacy.

OBJECTIVE To determine the feasibility of implementing a pharmacogenomics service in a community pharmacy. SETTING A single community pharmacy that is part of a regional chain known for offering innovative pharmacy services. PRACTICE DESCRIPTION Community pharmacists at the project site routinely provide clinical pharmacy services, including medication therapy management, immunizations, point-of-care testing, blood pressure monitoring, and diabetes education. PRACTICE INNOVATION The implementation of a pharmacogenomic testing and interpretation service for the liver isoenzyme cytochrome P450 2C19. PARTICIPANTS 18 patients taking clopidogrel, a drug metabolized by CYP2C19. MAIN OUTCOME MEASURES Rate of patient participation, rate of prescriber acceptance of pharmacist recommendation, time to perform genetic testing service, and number of claims submitted to and paid by insurance. RESULTS Of 41 patients taking clopidogrel and meeting project criteria, 18 (43.9%) enrolled and completed testing and interpretation of pharmacogenomic results. The mean time pharmacists spent completing all stages of the project with each participant was 76.6 minutes. The mean time to complete participation in the project (time between person's first and second visit) was 30.1 days. Nine patients had wild-type alleles, and pharmacists recommended continuation of therapy as ordered. Genetic variants were found in the other nine patients, and all pharmacist recommendations for modifications in therapy were ultimately accepted by prescribers. Overall, 17 patients consented to filing of reimbursement claims with their insurers. Five were not able to be billed due to submission difficulties. Of the remaining 12, none was paid. CONCLUSION A pharmacogenomics service can be an extension of medication therapy management services in a community pharmacy. Prescribers are receptive to having community pharmacists conduct pharmacogenomics testing, but reimbursement is a challenge.

An evaluation of pharmacogenomic information provided by five common drug information resources.

INTRODUCTION: This study evaluated whether pharmacogenomic information contained in the Food and Drug Administration (FDA)-approved package inserts of sixty-five drugs was present in five drug information resources. METHODS: The study searched for biomarkers from the FDA package inserts in 5 drug information sources: American Hospital Formulary Service Drug Information (AHFS), Facts & Comparisons 4.0 (Facts), ePocrates Online Free (ePocrates Free), Lexicomp Online (Lexicomp), and Micromedex 2.0. Each resource had the opportunity to present biomarker information for 65 drugs, a total of 325 opportunities. A binary system was used to indicate presence or absence of the biomarker information. A sub-analysis was performed on the 13 most frequently prescribed drugs in the United States. RESULTS: Package insert biomarker information was available, on average, for 81.5% of the 65 FDA-listed drugs in 2011. Percent availability for the individual resources was: Lexicomp, 95.3%; Micromedex 2.0, 92.3%; Facts, 76.9%; AHFS, 75.3%; and ePocrates Free, 67.7%. The sub-analysis of the 13 top drugs showed Lexicomp and Micromedex 2.0 had the most mentions, 92.3%; ePocrates Free had the least, 53.8%. CONCLUSION: The strongest resource for pharmacogenomic information was Lexicomp. The gap between Lexicomp and ePocrates Free is concerning. Clinicians would miss pharmacogenomic information 6.6 times more often in ePocrates Free than in Lexicomp. IMPLICATIONS: Health sciences librarians should be aware of the variation in biomarker availability when recommending drug resources for licensing and use. Librarians can also use this study to encourage publishers to include pharmacogenomics information from the package insert as a minimum standard.

Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.

BACKGROUND: The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males. METHOD: A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h. RESULT: In this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0-48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC(0-∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial. CONCLUSION: The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TNC-10000898.

Genes and beans: pharmacogenomics of renal transplant.

Advances in the management of patients after solid organ transplantation have led to dramatic decreases in rates of acute rejection, but long-term graft and patient survival have remained unchanged. Individualized therapy after transplant will ideally provide adequate immunosuppression while limiting the adverse effects of drug therapy that significantly impact graft survival. Therapeutic drug monitoring represents the best approximation of individualized drug therapy in transplant at this time; however, obtaining pharmacogenomic data in transplant patients has the potential to enhance our current practice. Polymorphisms of target genes that impact pharmacokinetics have been identified for most immunosuppressants, including tacrolimus, cyclosporine, mycophenolate, azathioprine and sirolimus. In the future, pre-emptive assessment of a patient's genetic profile may inform drug selection and provide information on specific doses that will improve efficacy and limit toxicity.

NAVAGATE: a rubric to move from pharmacogenomics science to pharmacogenomics practice.

Integration of pharmacogenomic data at the point of care is the next essential step in translating years of research into evidence-based decisions that impact the care of an individual patient. The use of clinical recommendations for pharmacogenomic data help clinicians to better select and monitor drug therapy. However, a systematic rubric for utilizing the data ensures a thorough implementation of the information in a way that may improve the application of the new scientific discoveries. NAVAGATE is a set of eight questions to ask when considering a pharmacogenomic test or test result when caring for a patient. The series of questions are meant to inform prescribing or dispensing when obtaining or employing pharmacogenomic data for these steps within the medical-care framework. In this article two key examples are used to exemplify the benefits of following a systematic process to evaluate the utility of the new scientific data.

Exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy.

AIM: To describe the exploratory planning and implementation of a pilot pharmacogenetic program in a community pharmacy. An institutional review board-approved protocol for a clopidogrel pharmacogenetic program in a community pharmacy was developed to address feasibility and evaluate the pilot program. STUDY CONCEPT: Subjects taking clopidogrel are asked to participate at the point of medication dispensing. A pharmacist schedules an appointment with subjects to discuss the study and collects a buccal swab sample for CYP2C19 testing. When the results are available, the pharmacist consults with the subject's prescriber regarding test result interpretation and associated recommendations, and schedules a second appointment with the participant to discuss results and review any physician-approved therapeutic changes. The intervention-associated consultation is then billed to the subject's insurance. RESULTS: Subject enrollment has begun. CONCLUSION: Community pharmacists may be valuable partners in pharmacogenetics.

Pharmacogenetics of drugs withdrawn from the market.

The safety and efficacy of candidate compounds are critical factors during the development of drugs, and most drugs have been withdrawn from the market owing to severe adverse reactions. Individuals/populations with different genetic backgrounds may show significant differences in drug metabolism and efficacy, which can sometimes manifest as severe adverse drug reactions. With an emphasis on the mechanisms underlying abnormal drug effects caused by genetic mutations, pharmacogenetic studies may enhance the safety and effectiveness of drug use, provide more comprehensive delineations of the scope of usage, and change the fates of drugs withdrawn from the market.

Knowledge, attitudes and education of pharmacists regarding pharmacogenetic testing.

AIM: Pharmacists are positioned to provide medication counseling and drug information to patients. This study assessed the knowledge, attitudes and education of over 700 pharmacists concerning pharmacogenetics and pharmacogenetic testing. METHODS: A multiquestion, online survey was developed to assess healthcare provider knowledge, attitudes and education concerning pharmacogenetic testing. RESULTS: More than 90% of pharmacists were interested in learning more about pharmacogenetics and testing, with those with less than 10 years of experience were more likely to want web-based continuing education programs. The pharmacists were unlikely to have had formalized education regarding pharmacogenetics, were very likely to rate their knowledge accurately, and were more likely to have a positive attitude about pharmacogenetics if they had received education regarding pharmacogenetics. CONCLUSION: Most pharmacists were interested in learning more about pharmacogenetic testing.

Can pharmacogenomics improve malaria drug policy?

Coordinated global efforts to prevent and control malaria have been a tour-de-force for public health, but success appears to have reached a plateau in many parts of the world. While this is a multifaceted problem, policy strategies have largely ignored genetic variations in humans as a factor that influences both selection and dosing of antimalarial drugs. This includes attempts to decrease toxicity, increase effectiveness and reduce the development of drug resistance, thereby lowering health care costs. We review the potential hurdles to developing and implementing pharmacogenetic-guided policies at a national or regional scale for the treatment of uncomplicated falciparum malaria. We also consider current knowledge on some component drugs of artemisinin combination therapies and ways to increase our understanding of host genetics, with the goal of guiding policy decisions for drug selection.

Pharmacogenetics and rational drug use around the world.

The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.

Global formulary review: how do we integrate pharmacogenomic information?

OBJECTIVE: To summarize a standard formulary decision process and provide recommendations for the integration of pharmacogenomic (PGx) information within the formulary decision-making process. DATA SOURCES: With use of MEDLINE (1920-March 2010), the terms "formularies, hospital" and "pharmacogenetics" were searched in the MeSH database, yielding no results. The MeSH terms were then searched separately in addition to searching for "rational drug therapy" and "essential medicines list" through the main PubMed database. STUDY SELECTION AND DATA EXTRACTION: Articles deemed relevant to both terms were assessed, interpreted, and incorporated as key pieces to the review of formularies and the integration of PGx information as a part of the formulary review process. The articles referenced were deemed appropriate and categorized into 5 areas: formulary management systems and pharmacy and therapeutics (P&T) committees, international formularies, formulary decision-making, PGx evidence, and recommendations regarding integrating PGx into formulary decision-making. DATA SYNTHESIS: The field of PGx is rapidly evolving as the evidence supporting genetically guided individualized therapy continues to grow. To bring this evidence from the bench to the bedside, institutions will need to evaluate PGx data to integrate individualized therapy into practice. Few standardized methods exist to analyze and apply clinical PGx data and incorporate the information into drug evaluation at the formulary level. Several online sites provide resources to aid in formulary review and can be used when incorporating clinically relevant PGx information into a formulary decision. In addition, there are key questions that organizations can ask as they evaluate the PGx information in each step of the decision-making process. CONCLUSIONS: P&T committees should formulate a plan to integrate a search for pharmacogenomic data with each drug evaluation and integrate the results into the formulary decision process to enhance the appraisal of drug efficacy, safety, and cost.

Applying the genome to national drug formulary policy in the developing world.

With pharmacogenetics comes the promise of individualized therapy selection for many common diseases where multiple treatment options are available. Recent advances including the Human Genome Project, the International HapMap project, advances in throughput technology and reduction in cost of genetic testing, and the inclusion of genotype-related dosing recommendations into package inserts all point to the integration of pharmacogenetics into clinical practice. However, many countries will not have access to pharmacogenetics resources to individualize patient therapy for decades to come. The PharmacoGenetics for Every Nation Initiative (PGENI) is a first step to making pharmacogenetics applicable on a global level. Generation of genotype profiles for 'common' population groups within a country will provide a useful, but not perfect resource for incorporating pharmacogenetics into national drug formularies in the form of prioritization or tailored surveillance recommendations for a country's population. Targeted educational efforts will also prepare the Ministry of Health staff from participating countries to better integrate genetic information into many areas of healthcare, including disease management and therapeutic development. The goal should always be optimizing therapy for each individual patient, but pharmacogenetics can be useful now and essential in the future for the developing world.

Institutional profile. UNC Institute for Pharmacogenomics and Individualized Therapy: interdisciplinary research for individual care.

The Institute for Pharmacogenomics and Individualized Therapy (IPIT) at the University of North Carolina at Chapel Hill (NC, USA) is a collaborative, multidisciplinary unit that brings together faculty from different disciplines and crosses the traditional departmental/school structure to perform pharmacogenomics research. IPIT investigators work together towards the goal of developing therapies to enable the delivery of individualized medical care. The NIH-supported Comprehensive Research on Expressed Alleles in Therapeutic Evaluation (CREATE) group leads the field in the evaluation of pathways regulating drug activity, and also provides a foundation for future IPIT research. IPIT members perform bench research, clinical cohort analysis and prospective clinical intervention studies, research on the integration of pharmacogenomic therapy into practice and research to foster global health pharmacogenomics application through the Pharmacogenetics for Every Nation Initiative. IPIT Investigators are actively incorporating a pharmacogenomics curriculum into existing teaching programs at all levels.

Cytochrome P450 enzymes and genotype-guided drug therapy.

The cytochome P450 enzyme system is responsible for the metabolism of xenobiotics, including > 75% of commonly prescribed medications. Many of the cytochrome enzymes exhibit polymorphic genotypes, partly accounting for the variations observed in individual drug responses. Recent advances in the understanding of functional alleles of cytochrome P450 enzymes have changed the use of medications. Improvements in drug efficacy and the prevention of toxicity, as well as improvements in clinical drug dosing, have enhanced pharmacotherapy decisions in medical practice. In addition to personalizing medicine, the identification and quantification of genotypic differences in cytochrome P450 metabolism has the potential to facilitate population-based personalized medicine in countries without the resources to perform genotypic tests at the point of care. This review provides an update on the utility of genotype-guided therapy when treating breast cancer, malaria and coagulation disorders. Also discussed are advancements made in diagnostic tests for cytochrome genotypes and the need for future research in the area of diagnostic tests.