The benefits of genetic testing for medication

In this modern era of healthcare, advancements in Pharmacogenomics (PGx) have opened up new avenues for personalized medicine. What is Pharmacogenomics? Sounds like a mouthful, but when we break it down it’s the combination of the words Pharmacy + Genes. By studying how an individual’s genes influence their response to medications, PGx aims to improve drug safety and prescribing habits without you having to take a single pill. This could mean prescribing different doses of a medication, using alternative classes of drugs, or avoiding certain medications based on your body. Pharmacists and Genetic Counselors are driving the movement to bring PGx-guided medication management to our prescribers and communities because it’s become widely accessible and affordable in the US.

Let’s delve into the world of PGx and explore its profound benefits for patients, healthcare providers, and the healthcare system as a whole.

What is Pharmacogenomics?

Pharmacogenomics (PGx) utilizes genomic information to assess an individual’s response to certain medications. A drug may work wonderfully for yourself, but it could be potentially fatal for your neighbor and PGx is here to stop that! Although our DNA tells us every human being is 99% the same, it’s that 1% difference that explains the differences in how we respond to medications. Prescriptions play an important role in health care and can be used to treat a wide range of chronic conditions to help people get better and feel better. However, medications can also be dangerous if they are not used properly, which is why Pharmacogenomics (PGx) is continuing to gain attention as researchers discover the impact of genetic changes on medication response. Some drugs are broken down by our liver, and some are broken down by kidneys. Not all drugs have a PGx related effect, so when we are discussing medications that have a genetic effect, we are talking about medications processed by our liver, and the differences in how we absorb, break down, and eliminate these drugs. Let’s look at the timeline of medication use and where PGx will take precision medicine going forward.

What is the difference between Pharmacogenomics and Pharmacogenetics?

Pharmacogenetics focuses on understanding the genetic factors behind individual variances in drug response. On the other hand, pharmacogenomics explores the combined effects of multiple mutations in the genome that can potentially influence a patient’s reaction to drug treatment. In essence, pharmacogenomics extends the scope of pharmacogenetics by examining variations in multiple genes that are linked to variability in drug response.

A brief history on medication use in the US

1960s-1970s:

During this era, medication prescribing was primarily based on clinical judgment and empirical evidence. Healthcare providers relied heavily on their own experiences and observations when selecting and dosing medications for patients. Limited access to patient-specific data and genetic information made personalized prescribing challenging. This era also saw the introduction of many new medications, including antibiotics, antidepressants, and antipsychotics, where a good bit of these medications are cleared by our liver. These medications were often prescribed for a wide range of conditions, and there was a general lack of understanding of their long-term effects. By the 1970s, there was a growing awareness of the risks of medication harm, and there were calls for more transparent consumer education and quality control from drug manufacturers by the FDA.

1980s-1990s:

The 1980s and 1990s saw the emergence of evidence-based medicine and the utilization of clinical trials. Randomized controlled trials (RCTs) became the gold standard for evaluating medication efficacy and safety. Guidelines and protocols based on RCTs provided healthcare providers with standardized recommendations for medication prescribing. This led to a more cautious approach to prescribing, and there was a decline in the use of some medications that had been shown to be ineffective or harmful, however, these guidelines often focused on average responses and did not account for individual genetic variations. The 1990s saw the development of new technologies, such as pharmacogenomics, which allowed doctors to better understand how individual patients respond to medications. This led to the development of more personalized prescribing practices, and there was a decline in the use of “one-size-fits-all” approaches to treatment in medicine.

2000s-2010s:

Advancements in genetics and molecular biology began to shape medication prescribing practices during this period. There was also a growing focus on patient safety, and there were efforts to reduce the risks of adverse drug events. Enter Pharmacogenomics (PGx), which gained attention as researchers discovered the impact of genetic variations on medication response. PGx aimed to personalize medicine by identifying genetic markers associated with drug metabolism, efficacy, and safety. However, widespread implementation of PGx remained limited, and its incorporation into clinical practice was not standardized.

As a trained PGx Consultant Pharmacist with GeriatRx, I can’t stress enough how vital having your genes tested to improve drug selection can prevent harm and even death. PGx has helped our practice uncover rare clotting disorders, increased risk of fatal allergic reactions, develop an understanding of why our patients have failed multiple medications, and even explain why some patients have been sent to the Emergency Room after being prescribed the clinically recommended medication. This type of information is critical for prescribers to be aware of, however, prescribers are not currently being trained on this, so we often use PGx as a teaching opportunity for them to improve patient care. The FDA has even started to require that drug developers document whether there are genetic markers worth noting before drugs come to market.

Present:

In recent years, there has been an increased emphasis on precision medicine and personalized healthcare. Rapid advances in genetic testing technologies and bioinformatics have made PGx more accessible and cost-effective. Not to mention it’s allowed my practice, GeriatRx to grow and serve more of our rural and underserved aging population, who may have not been offered this unique type of clinical guidance in their earlier years. Using PGx has allowed me to help clinicians deprescribe harmful medications while keeping our older adults out of the hospital and aging gracefully in their homes with family. Healthcare providers now have the opportunity to incorporate patient-specific genetic information into medication prescribing decisions. Because of the work of medical lab testing, pharmacists, and modern medicine, PGx testing is gradually being integrated into clinical practice, particularly in specialties such as oncology, psychiatry, and cardiology, where more team-based integration of a pharmacist in care has cut patient health costs.

Additionally, digital health technologies, electronic health records, and clinical decision support systems are being utilized to facilitate personalized prescribing. These tools assist healthcare providers in accessing patient-specific information, including genetic data, and support evidence-based medication decisions. The goal is to optimize treatment outcomes, minimize adverse reactions, and enhance patient safety through tailored prescribing approaches. More importantly, we all want to know that what we are putting into our bodies are safe, before waiting for an accident to happen. PGx is the tool for medicine to switch from being reactive, to proactive in patient care.

Overall, there has been a significant shift in the way that medicine has been prescribed over the past 60 years. Looking ahead, ongoing advancements in genetics, technology, and data analytics will likely continue to shape the future of medication prescribing. With the increasing integration of PGx and personalized medicine approaches, healthcare providers can anticipate more individualized treatment plans based on patients’ unique genetic profiles and other relevant clinical information.

Understanding genetic variations and their impact

Let’s say you’re an ordinary person in the UK who has never thought about PGx before. You’re prescribed a new medication for chronic pain management. You take the medication as directed, but you don’t seem to be getting any better. In fact, you start to feel worse due to severe nausea, hives, and oversedation.

You go back to your doctor, who tells you that you may be one of the people who doesn’t respond well to this medication. Your doctor orders a PGx test using NowPatient, which reveals that you have a genetic variant that makes you more likely to experience serious side effects from this medication.

Your doctor is able to prescribe a different medication that is more effective for you and has fewer side effects. As a result, you’re able to control your chronic pain and feel better.

This is just one example of how PGx can help everyone in the UK to get the best possible care. As the field of PGx continues to expand, NowPatient will make this become even more common for people to have their genetic information taken into account before they’re prescribed medications, and all it takes is a simple pharmacogenomic test using a non-invasive cheek swab to collect the sample.

Decoding genetic influences on medication response

As you know, everyone’s DNA is unique. This genetic variation can affect how our bodies process and respond to medications. For example, some people may be more likely to experience adverse reactions to certain drugs, while others may not respond to a drug at all.

Genetic variations play a crucial role in drug absorption, metabolism, efficacy, and safety. For example, some people have genetic variations that make them more likely to absorb medication too quickly. This can lead to high levels of the medication in the bloodstream, which can increase the risk of side effects. Other people have genetic variations that make them more likely to break down a medication too slowly, which can lead to low levels of the medication in the bloodstream and can make the medication less effective. PGx helps identify these genetic variations so that healthcare providers can tailor treatment approaches accordingly.

It is important to note that genetic variations are not the only factor that affects drug response. Other factors, such as age, weight, drug interactions, drug-gene interactions, health conditions, and liver function, can also play a role. This is why it’s important to ensure your pharmacist and health care team are well aware of all prescription and Over-the-counter meds, herbals, vitamins, and supplements are communicated and cross-checked with PGx considered. However, genetic variations can be a significant factor in drug response, and they should be considered when prescribing medications.

By identifying these variations through PGx testing, NowPatient can help healthcare providers gain valuable insights into how patients will respond to specific medications, enabling them to make informed decisions and personalize treatment approaches accordingly.

Introduction to CYP2D6 and CYP2C19 testing

Pharmacogenetic testing and the use of testing in clinical practice is a relatively new, evolving and complex topic.

Drug metabolism is the chemical breakdown of a drug by specialized enzymatic systems. There are two genes that are highly involved in drug metabolism. These genes are CYP2D6 and CYP2C19 and they are both associated with Cytochrome P450 (CYP) system which promotes drug metabolism (breakdown of drugs). The CYP2D6 gene encodes the enzyme Cytochrome P450 2D6 (CYP2D6) and the CYP2C19 gene encodes the enzyme Cytochrome P450 2C19 (CYP2C19).

CYP2D6

The CYP2D6 enzyme which found mostly in the liver and brain is responsible for the metabolism of commonly prescribed drugs such as:

• Antidepressants
• Antipsychotics
• Beta-blockers
• Opioids
• Antiarrhythmic medications

Therefore, your psychiatric or your cardiovascular medication may not work as expected because of your personal CYP2D6 enzyme activity.

CYP2C19

CYP2C19 enzyme is associated with the metabolism of the following drug groups:

• Proton Pump Inhibitors
• Anti-Epileptic drugs
• Blood thinners (e.g. Warfarin)
• Anti-Malarials
• Anxiolytics

How do my genes affect my response to medications?

The CYP2C19 and CYP2D6 genes generate a set of instructions which allow your body to produce CYP2C19 and CYP2D6 enzymes. Small changes in the CYP2C19 or CYP2D6 genes can change how well the CYP2C19 and CYP2D6 enzymes work to break down medications.

Therefore, by testing the genes, we can ascertain if you fall into the following groups:

• Ultrarapid Metabolizer
• Rapid Metabolizer
• Normal Metabolizer
• Intermediate Metabolizer
• Poor Metabolizer

If you are an ultrarapid metabolizer it could mean that the drug you take could be metabolized quickly and therefore there may be a reduced or diminished clinical effect. However, if you are a poor metabolizer then the drug you take could build up because it is not being metabolized effectively and this could lead to clinical side-effects being experienced.

Why get tested?

Testing can be useful to help evaluate your personal response to a particular drug. For example, with the antiplatelet drug clopidogrel, it is metabolized by CYP2C19 enzymes. Therefore, if we can test for variations in the gene (CYP2C19) that codes for the CYP2C19 enzyme, then the dose of the drug could be adjusted depending on if you are ultrarapid, rapid, normal, intermediate or poor metabolizer.

What is the NowPatient PGx service?

As a user of NowPatient, we use Artificial Intelligence (AI) to determine if the medication that you use is sensitive to CYP2C19 and CYP2D6 genes.

We use CPIC (Clinical Pharmacogenetics Implementation Consortium) and PharmGKB as our evidence base and implementation framework. If you are eligible we would can offer you a private PGx test. You would only qualify for the service if the following two conditions are met:

• Your medication metabolizism is sensitive to enzymes related to the CYP2C19 and CYP2D6 genes
• You are not responding to the medication as expected

PGx testing allows for the prediction of unfavorable drug reactions or reduced effectiveness, which ultimately results in enhanced health outcomes and reduced expenses for the health system. Approximately 99% of individuals possess actionable variants in PGx related genes, and research indicates that up to 55% of adults receive prescriptions for drugs that have available PGx guidelines and may be eligible for a PGx test.

After you place the order for your test, we will send you out a home test kit. You will need to supply a cheek swab sample and then return it to our laboratory in the pre-paid envelope.

Once the laboratory finalises the results, the test results are uploaded to the account section of the NowPatient App. However, it remains locked. You will be invited to book a video consultation with one of our highly trained PGx clinicians. The clinician will be able to explain the results and what they could mean for you. You will also be explained the limitations of the service, as well as the benefits. At the end of the video consultation, the clinician will ‘unlock’ the results and you will then be able to download them and share the results with your doctor.

The results could mean that the doctor changes the standard dose of the medication prescribed to you, or alternatively, change your medication altogether.

Benefits of PGx for patients

There are many potential benefits of PGx for patients. By understanding how an individual’s genetic makeup influences their response to medications, PGx offers numerous benefits that enhance patient outcomes, improve safety, and contribute to more efficient healthcare practices. Let’s explore some of the key advantages of PGx in personalized medicine. These benefits include:

1. Personalized Medicine: PGx is at the forefront of personalized medicine. By analyzing an individual’s genetic makeup, PGx identifies genetic variations that influence how the body processes and responds to medications. Why waste time with trial and error if we can affordably get a clear answer with genetic testing? This information allows healthcare providers to tailor treatment plans according to each patient’s specific genetic profile, maximizing the effectiveness of medications. Personalized medicine through PGx ensures that patients receive treatments that are most likely to work for them, taking into account their unique genetic characteristics
2. Improved drug response and efficacy: PGx testing can identify genetic variations that impact an individual’s response to specific medications. This means less time failing a medication and coming back in three months, or suffering in silence from a medication side effect and eventually stopping it without informing the provider. This information can be used to personalize drug selection and dosing, which can maximize treatment effectiveness. This means the patient is happy, the provider is happy, and the health system is happy! This personalized approach maximizes treatment effectiveness by tailoring therapy to each person’s unique genetic characteristics. As a result, patients experience improved drug response rates, enhanced symptom relief, and increased treatment success which means better client trust and satisfaction.
3. Enhanced safety and reduced adverse reactions: Genetic information can identify individuals at higher risk for adverse drug reactions. Certain genetic variations can make patients more susceptible to specific side effects or toxicities. By understanding these genetic predispositions, healthcare providers can avoid prescribing medications that may cause harm based on an individual’s genetic profile. This proactive approach reduces the likelihood of adverse reactions, minimizes patient discomfort, and ensures a safer medication experience
4. Avoidance and reduction of the trial-and-error approach: Traditionally, finding the right medication and dosage for a patient often involved a trial-and-error process. This approach can be time-consuming, frustrating, and potentially dangerous. PGx testing eliminates the need for such guesswork by providing valuable insights into an individual’s genetic predispositions. By considering a patient’s genetic profile, healthcare providers can more accurately predict how an individual will respond to a specific medication, thereby avoiding unnecessary experimentation. This leads to faster identification of effective treatments, minimizes unnecessary side effects, and reduces the overall burden on patients

Benefits of PGx for healthcare systems

There are also potential benefits of PGx for the healthcare system. These benefits include:

• Cost savings: PGx-guided prescribing can help avoid ineffective or potentially harmful medications, reducing healthcare costs
• More efficient drug development: PGx data can contribute to the development of new drugs or the repurposing of existing medications. This could lead to more targeted therapies that consider genetic factors
• Reduced Health Costs from Suboptimal or Harmful Medications: Suboptimal or harmful medications not only compromise patient health but also contribute to increased healthcare costs. Adverse drug reactions, ineffective treatments, and hospitalizations resulting from inappropriate medications can lead to substantial financial burdens. PGx helps identify individuals who are at higher risk of adverse drug reactions or poor response to certain medications based on their genetic variations. By avoiding the use of medications that may be suboptimal or harmful for a particular patient, PGx reduces healthcare costs associated with ineffective treatments, adverse events, and unnecessary hospitalizations.
• Increased Patient Confidence in Their Care and Improved Mortality/Hospital Admissions/ER Visits: PGx enhances patient confidence by providing a more personalized and tailored approach to medication therapy. When patients are aware that their healthcare provider is taking their unique genetic makeup into account when prescribing medications, it instills trust and confidence in the treatment plan. Furthermore, by avoiding adverse drug reactions and ineffective medications through PGx-guided prescribing, patient outcomes can be significantly improved. This, in turn, can lead to reduced mortality rates, fewer hospital admissions, and fewer emergency room visits. Patients can feel more confident in their care knowing that their medications are selected with their specific genetic profile in mind, increasing the likelihood of positive outcomes and minimizing unnecessary healthcare utilization

PGx is a transformative field that directly addresses the potential benefits of personalized medicine. NowPatient aims to provide these benefits to include reduced costs and errors from suboptimal medication use, improved patient confidence in their care, and better mortality rates and reduced hospital admissions and ER visits.

Current implementation and future potential of PGx

In addition to the potential benefits of PGx, it is also being implemented in clinical practice across the US and beyond. It is used to guide medication selection, dosing, and management for various conditions. For example, PGx is being used to guide the treatment of breast cancer, cardiovascular disease, and HIV/AIDS. Ongoing pharmacogenomics research and advancements in the field continue to expand our understanding of the relationship between genetics and drug response, promising even greater integration of PGx into routine healthcare practices. The future of personalized medicine through PGx holds immense potential to transform the healthcare landscape.

Summary

PGx is a promising new field of research with the potential to revolutionize the way we treat diseases. By considering an individual’s genetic makeup, PGx implementation with NowPatient can help to personalize medicine and improve patient outcomes.

• Single Molecule Real-Time Sequencing (SMRT)
• Pharmacogenomics
• Table of Pharmacogenetic Associations
• Pharmacogenetic genotype and phenotype frequencies in a large Danish population-based case-cohort sample
• Table of Pharmacogenomic Biomarkers in Drug Labeling

About Dr. DeLon Canterbury

Recognized as “The Deprescribing Pharmacist” and Top 50 Most Influential Pharmacists in the US, Dr. Canterbury created GeriatRx as a Deprescribing and Precision Medicine consulting service for older adults and caregivers after witnessing his parents manage his grandmother, Mildred, and her decline with dementia due to an inappropriately prescribed antipsychotic from a nursing home. He decided to take these matters into his own hands by founding GeriatRx, a healthcare consulting company focusing on Side Effect Management, Deprescribing, and Precision Medicine testing to determine which medications will not work for you before taking a single pill! GeriatRx uses patient-centered methods that take the headache out of healthcare by providing cost-effective strategies to reduce harmful medications, and by empowering older adults and caregivers on how to fight back against a broken health care system while saving his clients thousands of dollars. He has also created the Deprescribing Accelerator helping to train pharmacists, nurses, and prescribers on how to leverage and monetize Deprescribing and Precision Medicine in clinical practice. GeriatRx works with your provider as a health care team, while you have your own personal, concierge pharmacist batting for you every step of the way.