Introduction to Pharmacogenomics in Pharmacy Practice

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1 Pharmacy Technician Education for Association Members By: Brad Tice PharmD, MBA, FAPhA Brad Tice received his bachelor of science in pharmacy from the University of Kansas in 1994 and his doctor of pharmacy degree in He also received a Masters of Business Administration from Vanderbilt University in He has been a leader within the profession of pharmacy over the last 20 years in implementing new pharmacy services. He currently works for Cardinal Health as a Director Marketing & Product Management in the Performance and Outcomes Practice Area and has started RxGenomix, LLC to integrate pharmacogenomics into pharmacy practice. He has also worked in Managed Care at Humana, Inc. as a clinical pharmacist overseeing the Adverse Event program and as Chief Clinical Officer for PharmMD, an MTM start-up and has started other companies related to pharmacy and information technology. Dr. Tice reports he is a major stock holder for RxGenomix, LLC. Off-label medications will not be discussed during this CPE activity. CEI has taken appropriate action for conflict resolution, including external review by a non-conflicted peer reviewer. CPE Information: Universal Activity Number: H01-T CPE Hours: 1 contact hour (0.1 CEU) Target Audience: Pharmacy Technicians Activity Type: Knowledge-based Initial release date: 1/1/2014 Planned expiration date: 12/31/2015 The Collaborative Education Institute is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. Activity Goal: This activity introduces the emerging area of pharmacogenomics, the application of genetic testing to medication use. Brief aspects of the pharmacology related to personalized medicine are introduced, in addition to sample collection, testing processes, and the impact on patients and their medication use. Learning Objectives: Upon successful completion of this knowledgebased CPE activity, pharmacy technicians should be able to: 1. Describe why pharmacogenomics is important to pharmacy practice and assisting patients and prescribers in identifying the most appropriate medications for them 2. List three mechanisms of action of medications that are affected by genetic variations 3. Describe a sample collection process that can easily be performed in the pharmacy 4. List four types of medications where genetic testing can improve medication use 5. Define SNP and communicate to a patient how SNPs affect individual s response to medications This activity has been developed specifically for pharmacy technicians and is one of 10 activities in the TEAM series. Introduction to Pharmacogenomics in Pharmacy Practice Introduction Pharmacogenomics, referred to as PGx, is an emerging science in the use of medications that is developing from the mapping of the human genome. It offers the ability to tailor a patient s medications based on their genetic profile and has the potential to transform pharmacy and medical practice. By tailoring medications to a patient s genetic profile, patients can be prescribed medications that are known to work for them more effectively and with fewer side effects. This can also be done from the outset of prescribing for the patient so there is less trial and error with the patient s medication regimen. The genetic mapping is known for many drugs 1,2. However, what is still emerging is the understanding of how to apply this to clinical practice with patients. There are some drugs that have clinical guidelines developed where the knowledge can be applied more readily. Pharmacy technicians can play a large role in several aspects of the application of this science, including the identification of patients that can benefit, the communicating of the need and opportunity to patients, assisting with sample collection for the test and assistance with billing practices. Overview The Human Genome Project began in 1990 with the goal of mapping the entire human genome by sequencing all of the three billion bases of deoxyribonucleic acid (DNA) within the entire human genome and to find all of the estimated 20,000 to 25,000 human genes 3. This knowledge could then be used to gain a better understanding of the makeup of the human body to apply to scientific and medical advancement. The project was completed two years ahead of schedule with the project being formally completed in Now that the initial effort is complete, the work is being done to put this knowledge to meaningful use. One of the major areas it has been believed

2 that advances can be made is with health care. Now that the sequences of individuals are known, this knowledge is being applied to identify differences in people and to map those differences to medical conditions and responses to medications. This knowledge is also being used help identify cures for diseases and to develop medications specific to the medical conditions. Understanding the Terminology One of the challenges of understanding, applying and communicating this new science of pharmacogenomics is grasping and becoming comfortable with the terminology 4. As with any new area, especially one as technical as the human genome, the terms used will likely seem new to pharmacy technicians and pharmacists. At the same time, pharmacy technicians and pharmacists can also become a resource for patients and other health care providers as the terms and science are also new for others. By learning this new area while it is emerging, pharmacy technicians and pharmacists can distinguish themselves and further build their credibility and stature as medication experts. Here are some basic definitions to help get started: Term Phenotype Single Nucleotide Polymorphism (SNP) Allele Heterozygous Homozygous Pharmacogenomics Definition An individual s expression of a physical trait as a result of that person s genetic makeup. A variant DNA sequence in which a single nucleotide is replaced by another base, such as cytosine (C) replacing thymine (T). An alternative form of a gene inherited from each parent. Possessing two different alleles for the same trait. Possessing identical alleles for the same trait. The study and application of genetics in the use of medications and response to drug therapy One of the main ways that individuals respond differently to medications based on their specific genome is by having different rates that they metabolize the medications. This can happen based on differences in the metabolism of the drug due to having differences in enzymes that process the drugs and differences in how the drug triggers receptors on cells or are transported into the cells to work. Because of these differences, patients are usually categorized based on their rate of metabolism, known as metabolizer phenotypes. The typical categories can be seen in table 1. These different phenotypes will be specific to different pathways that drugs are metabolized, meaning a patient will have different types of phenotypes for different drugs. Generally, these phenotypes will apply to all medications that are affected by the same pathway. However, it may be possible for there to be individual responses to drugs within each grouping, especially based on other medications they are taking. Patient Pharmacogenomic-Based Metabolizer Phenotypes Ultrarapid Metabolizer (UM) Extensive (Normal) Metabolizer (EM) Intermediate Metabolizer (IM) Poor Metabolizer (PM) Table 1. Metabolizer phenotypes When applied to the metabolism of an active form of medications, these variations can result in different responses to medications where someone who is an ultrarapid metabolizer (UM) is likely to have lower concentrations of the drug and may be considered a treatment failure, whereas someone who is a poor metabolizer (PM) may have higher than expected drug concentrations resulting in toxicity. This would mean that a patient who is an UM would require a higher dose of a drug to get the expected results from a medication as their body eliminates the drug faster. An individual who is a PM would require a lower dose of a drug to achieve therapeutic concentrations. Conversely, if the drug is not in its active form when entering the body and must be altered by the body to be in its active form, the opposite would be true (i.e. this type of drug is called a prodrug and includes drugs like Plavix, known as clopidogrel). Other examples of common medications that are altered by various mechanisms include codeine, tricyclic antidepressants such as amitriptyline, and simvastatin. Knowing the patient s genetic profile and related metabolic phenotype in advance of treatment can aid in helping the patient avoid these undesirable situations and enable the clinician to treat the patient more effectively. Many of these differences are specific to metabolizing enzymes of the cytochrome P450 Family (CYP450). Pharmacists and technicians will need to be able to communicate these terms as well. Table 2 breaks down the cytochrome P450 terms to enable pharmacists to communicate using them. These variations are most commonly caused by single nucleotide polymorphisms (SNPs; pronounced snips ). Pharmacy TEAM Series 2

3 These are single changes in a DNA (Deoxyribonucleic acid) sequence. DNA is comprised of four bases adenine (A), cytosine (C), guanine (G), and thymine (T). The sequence of these bases, in what is called the coding region, is responsible for generation of amino acid sequences which form proteins. The proteins of interest in pharmacogenomics are drug receptors, drug metabolizing enzymes, such as the previously mentioned CYP450 Family, and drug transporters. A change of one base to another in the DNA sequence can alter the amino acid sequence, which in turn may alter protein function. For example, part of the common base sequence may be AAGGCTAA, while an individual may have a variant base sequence of AAGGTTAA, where thymine (T) replaces cytosine (C). These single substitutions are what most commonly introduce variation in an individual s response to drug therapy. Not all variations are necessarily labeled SNPs and not all variations cause clinical differences. A variation must occur in at least 1% of the population to be labeled a SNP. Category Example using CYP2D6*4A Superfamily CYP (pronounced sip ) Family 2 Subfamily D Individual Member 6 Star * Allele 4 Suballele A Table 2. Explanation of Cytochrome P450 Naming Nomenclature. SNPs make up about 90% of all human genetic variations and are seen every bases along the three billion base human genome sequence. Therefore, SNPs can influence everything from individual characteristics to disease susceptibility to drug response. Collecting the Sample One of the reasons PGx testing can fit into pharmacy practice so well and that pharmacy technicians can play a significant role is that samples can easily be collected. Typically, samples of patients saliva are collected using either a test tube or a buccal cheek swab. Blood can be used, but it is not necessary to do such an invasive procedure. The touch of a patient is similar to that of an immunization, only without the needle, so it is envisioned that the patient experience will be very positive. With the buccal cheek swab procedure, a kit is used that has a cotton tip or foam sponge tip that looks similar to a cotton swab. The swab is inserted into the mouth and rubbed firmly against the inside of the cheek or between the gum and cheek or between the gum and the lower and upper lip. Commonly for collection, the cheek is rubbed for approximately one minute. The swab is then placed in a tube or envelope for storage and shipping to the laboratory for processing. With the saliva collection kit, patients spit into a test tube to provide enough saliva (approximately 5 ml) for testing. The volume of saliva can seem large to patients and it may be difficult for some patients to supply the needed volume. It may take five to ten minutes to collect the required volume. Once collected, the test tube is sealed and sent for testing. It is extremely important to handle the sample carefully to avoid contamination with another individual s DNA. If there is either contamination or if not enough sample is collected, the patient may be required to provide another sample, delaying results and increasing costs. Some experience has shown that failure rates when consumers are collecting on their own can be as high as 10%. This may be justification for collection being performed by trained health care professionals such as pharmacists or pharmacy technicians. While many of the traditional lab tests performed in a pharmacy require CLIA certification or a CLIA waiver certificate, no CLIA waiver approvals have been identified, possibly because of the newness of the tests, and patients are able to perform this collection on their own and at times in their own homes through kits that are marketed directly to consumers. Billing Considerations There are several aspects of the service that will need to be worked through regarding how the service is delivered and compensated as this new area emerges. One of these questions will be whether or not to test the patient on multiple pathways all at once or only test the patient for the specific pathway related to the medication under consideration at the current time. The reason for this is that it can be more cost-effective to run multiple pathways at one time and some third party payers may pay for an entire panel while others may pay for only the current specific pathway. However, if a patient is paying personally for the service, they may prefer to only pay for one test at a time. Additionally, as this science is emerging and the technology is quickly advancing, the costs of the testing are decreasing quickly as well. Where less than a decade ago it could be over Pharmacy TEAM Series 3

4 $100,000 to test a person s genome, the cost has recently decreased to around $1,000 per person. Challenges and Ethical Considerations As the health care system and health care practitioners work to implement this new knowledge into practice, there are many aspects that are unclear and will have to be worked through. One of these is how to determine what parts of the knowledge are meaningful in clinical practice versus what is just interesting scientific knowledge. Currently, the genetic mappings are available on over 50% of medications. However, clinical guidelines only exist for a handful of medication classes. Because of this, there can be resistance to the application in practice as clinicians have difficulty distinguishing between what is meaningful and understanding how to apply it in practice. Practitioners also may not want to change how they have been practicing medicine and may subsequently resist changing their practices without overwhelming evidence. Pharmacists will be important in these cases to help other practitioners understand the science that the recommendations are based on. Pharmacy technicians will be important to help support the pharmacists in these cases as well. Patients may also be concerned about the exposure of their genetic information and who may have access to it. Practitioners who are involved with genetic testing will have to ensure patients that their information is secure. An additional protection patients have is the Genetic Information Nondiscrimination Act of 2008, referred to as GINA 5. The law forbids discrimination and harassment on the basis of genetic information when it comes to any aspect of employment. Summary Pharmacy technicians can play a significant role in applying PGx in pharmacy practice. Through gaining knowledge of this new emerging area, pharmacy technicians can converse with patients about PGx and help them to understand the benefits it can bring to their medication use. Pharmacy technicians can also help pharmacists identify patients who are good candidates for testing and may be able to help with the collection of the sample and billing for the services provided. This can provide added roles for pharmacy technicians and can help further establish their value to the pharmacy practice. References 1. Accessed July 19, ResearchAreas/Pharmacogenetics/ucm htm 3. Accessed July 4, Kisor DF, Kane MD, Talbot JN, Sprague JE. Pharmacogenetics, Kinetics, and Dynamics for Personalized Medicine. 1st ed. Burlington, MA; Accessed August 3, Pharmacy TEAM Series 4

5 ASSESSMENT QUESTIONS: 1) Pharmacogenomics is important to pharmacy practice because A) It provides an opportunity for pharmacies to get patients on medications more specific to their needs and improve medical outcomes. B) It is a part of CMS Medicare Part D Medication Therapy Management service requirements. C) It provides an opportunity for pharmacies to increase revenues through selling more durable medical equipment (DME). D) It provides pharmacists a way to prescribe medications. 2) Pharmacy practice can be enhanced by incorporating pharmacogenomics A) Because pharmacogenomics provides another opportunity, similar to immunization delivery, for a patient touch-point that increases the connection to the patient. B) As pharmacists tell doctors how to prescribe medications, pharmacists will elevate themselves above doctors in the health care chain. C) Because patients will be excited to have their pharmacists override what their doctor tells them. D) Because pharmacy practices will automatically be able to bill for a health care service. 3) Genetic variations in individuals affect medications by altering A) Drug metabolism, transport into cells, and receptor reaction. B) Drug metabolism, dissolution in the stomach, and alterations of normal flora in the gut. C) Dissolution in the gut, transport into cells, and receptor reaction. D) Affecting the taste of medications causing them to be intolerable to be taken. 4) Differences in metabolism of medications caused by genetic variations A) Are caused by at least 20% of the genome of an individual varying from the normal population. B) Are caused only when a T thymine base is switched with a C cytosine base. C) Can be caused by the variation of a single base being altered. D) Are caused by any of the six different types of base pairs being altered. 5) Sample collections to test DNA require A) An invasive procedure performed in the pharmacy utilizing needles. B) Saliva or buccal cheek cells being collected. C) The use of a finger-stick similar to blood glucose monitoring. D) A sample of the patient s hair. 6) The sample collection for DNA should be easily performed in the pharmacy because A) It is most similar to a bone density test that is performed in the pharmacy. B) CLIA waiver certification is required similar to other tests performed in the pharmacy. C) The pharmacy technician can assist the patient. D) It does not matter how the test is handled to maintain accuracy. 7) One medication that enters the body as a pro-drug and must be converted to the active form but can be affected by genetic variations is A) Rosuvastatin B) Enalapril C) Warfarin D) Clopidogrel 8) Medications that are commonly prescribed in community pharmacy that also have altered metabolism include A) Codeine B) Propofol C) Influenza vaccine D) Amoxicillin 9) A SNP is a A) Super Next-generation Polymorphism B) Single Nucleotide Polymorphism C) Simple Nucleotide Polymorphism D) Supra Neo Plasticis 10) SNPs (pronounced snips) A) Occur in the entire genome sequence. B) Require a change in only a single base pair to affect an altered affect to a medication. C) Represent changes to the entire coding region of a gene to affect an altered affect to a medication. D) Must occur in over 10% of the population to be called a SNP. CPE INSTRUCTIONS: Pharmacy technicians must read this activity and successfully complete the exam (70% pass rate) and evaluation prior to December 31, 2015 using the following instructions: Login to MY PORTFOLIO on On the right of the title of this article, click on GO TO EXAM Upon successful completion of the exam, you will see a page with explanations to the exam questions. After reading through this feedback, scroll to the bottom of the page and click GO TO EVALUATION Complete the evaluation and click SUBMIT You can obtain your CPE Statement of Credit at If you have any questions about this process, please contact Cindy Smith, csmith@gotocei.org, Pharmacy TEAM Series 5