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Drug-Gene and Drug-Drug Interactions: How Science Could Help Personalize Your Treatment Plan

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If you’re taking more than one prescription medication, you’re not alone — and if you’re older, your medicine cabinet could be at capacity. More than 40 percent of older adults take five or more prescription medications, and nearly 20 percent take 10 or more.1

The more prescription medications you take, the more likely you could experience an adverse drug event (ADE).2 That’s an unexpected, potentially harmful reaction from one or more medications. ADEs have a number of subcategories, including events that don’t involve human error. These include:

  • Adverse drug reactions (ADRs) – When someone has an unwanted or harmful reaction after the administration of a drug or drugs under normal conditions of use.
  • Side effects – Any effect caused by a drug other than the intended therapeutic one, whether beneficial, neutral, or harmful. (This term is often used interchangeably with ADR, though there is a slight difference: A “side effect” implies that the effect is common, less harmful, and may not require discontinuation of therapy.)

There are also several ADEs that involve human error, too, including drug toxicity, ameliorable ADEs, potential ADEs, preventable ADEs.

Each year, ADEs account for nearly 700,000 emergency room visits and 100,000 hospitalizations. In fact, nearly 5% of hospitalized patients experience an ADE, making them one of the most common types of inpatient errors.3

ADEs can also lead to drug adherence and abandonment issues in certain patients. One study found that 50% of patients did not take their medications as prescribed, in part, due to not being given the proper information about their medications’ adverse effects.4 Findings also show that anywhere from 30% to 80% of psychiatric patients have abandoned drug therapy due to unwanted side effects.5

One common cause of an ADE: two prescription medications interacting with each other, resulting in an unwanted side effect. This is known as a drug-drug interaction.

There may be a lesser known reason behind poor reactions to medication too: your genetic makeup A drug-gene interaction occurs when a patient’s genotype affects their ability to absorb or process a drug.

The U.S. Food and Drug Administration (FDA) has categorized more than 100 medications—including the blood thinner warfarin and opioid pain relievers like codeine and tramadol—with the potential for harmful drug-gene interactions (aka pharmacogenomic associations).6 It’s estimated that more than 90% of people could have a genetic variation that may cause a drug-gene interaction.7

How can a clinician figure out whether a drug-gene interaction might occur in a patient? Through pharmacogenomic (or PGx) testing, which can detect changes in your DNA that may alter how you process or absorb drugs.

Genotyping can help clinicians better treat their patients.8

Genomind asked Josh Peterson, MD, to explain the intricacies of these two types of drug interactions. Dr. Peterson is a professor of biomedical informatics and medicine at Vanderbilt University’s School of Medicine and the director of the Center for Precision Medicine. He’s also the senior author of a recent report about how pharmacogenomic associations might affect therapy.

Genomind: What does pharmacogenomics mean?

Dr. Peterson: Pharmacogenomics is the study of how genetic variation can impact drug disposition or response. For example, a gene might influence how much drug accumulates in your bloodstream, or whether the drug will give you a severe side effect or have little of the intended effect. There are other clinical reasons you might have a side effect or the drug might accumulate, but we can predict the genome-informed effects because we can measure the genetics precisely.

What are drug-gene interactions? How common are they?

A drug-gene interaction describes a scenario where a patient’s genetic result could influence either what drug a clinician selects or the drug dosing. Even for healthy populations, somewhere between 15 percent and 20 percent of adults, and about half that for children, are prescribed a drug that has a potential drug-gene interaction.7

High-risk populations that take more drugs on average — or have specific comorbidities — may find that pharmacogenomics can provide information on changes in their DNA that impact at least one drug they are taking.

How do drug-gene interactions compare to drug-drug interactions?

Most clinicians are familiar with drug-drug interactions: when one drug impacts how another drug is metabolized or both drugs act on similar targets/receptors (These are generally referred to as pharmacokinetic and pharmacodynamic drug interactions, respectively). We have had systems in place to identify those on the prescribing side for more than 20 years. But as you might imagine, the data to identify drug-gene interactions is not necessarily available at the point of care in most cases.

[Editor’s note: That is why Genomind’s precision medicine software represents such a significant innovation. This dynamic tool allows providers to analyze complex gene-drug and drug-drug interactions in a single composite view. With Genomind’s software, providers can quickly identify interaction risks, incorporate environmental factors like smoking and coffee consumption, and assess alternative medication options. Having that more-complete picture is intended to help them optimize treatment. Want your provider to have access to this revolutionary technology? Help us register them for Genomind’s precision health platform today. Get started here.]

Is any population particularly susceptible to drug-gene interactions?

Populations with high medication burdens and populations who take certain classes of drugs that tend to have drug-gene interactions. One example would be transplant patients, because they require certain immunosuppressants (types of medication that lower or reduce your body’s immune system response) with well-known drug-gene interactions that have a major impact on dosing or the way that patients tolerate those treatments.

Another group with important drug-gene interactions are patients with mental health disorders, everything from depression to diagnoses such as bipolar disorder or schizophrenia. Those medications often have relevant drug-gene interactions.

Are some drugs more prone to these interactions than others?

Like many other institutions that are using pharmacogenomics, we follow the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. CPIC has organized drugs into different categories based on how much they’re affected by genetics. Level A drugs are those for which there is strong evidence that genetic variations have an impact on drug response.

How often is pharmacogenomic testing employed today?

It varies widely from health system to health system. In general, it’s used in a small minority of cases, compared to when it could be used, so the potential for growth is great. That said, there are institutions that already utilize pharmacogenomic data on a regular basis. They usually run a panel test in their lab. There are a number of specialties in which the standard of care now includes pharmacogenomic tests prior to prescribing a drug to a patient, in order to inform how that prescription should be dosed or what drug should be selected.

What are the barriers to increasing pharmacogenomic testing?

It’s a relatively new field with complex results, and that complexity is not well understood at the point of care compared to the standard labs we’ve been using our whole careers. Secondly, the test can be costly. One major barrier right now is reimbursement. It’s not universal in most cases, so it can be unpredictable. With certain drugs it’s becoming a lot better. [Editor’s note: Learn about the cost of Genomind pharmacogenomic testing here.]

Another barrier is the level of evidence that payers and some providers seek. Many are holding off on incorporating pharmacogenomics until randomized controlled trials demonstrate improved health outcomes. A growing number of randomized controlled trials are proving or suggesting the benefit of genotype-tailored therapy. [Editor’s note: These include Genomind’s.]

Are there any drugs or disorders that offer a good case study?

A classic pharmacogenomic-use case involves the antiplatelet drug clopidogrel, used in patients with heart disease, particularly after a stent has been inserted. That drug is metabolized by the liver enzyme CYP2C19, which has a gene that encodes it. We know that if you have a variant in that gene of a certain type, then you may either process the clopidogrel too fast or you may process it too slow. In both cases, there can be adverse outcomes for the patient. That’s well documented, has a growing role in cardiovascular care, and is reimbursed more consistently in the last couple of years.

Do you foresee pharmacogenomics becoming more common over the next few decades?

Yes, I do. For example, we’re running four trials right now as part of the Implementing Genomics in Practice [IGNITE] network. Three of them are related to pharmacogenomics, specifically targeting depression, chronic pain, and acute pain after an elective operation. If the trials show a benefit from pharmacogenomics, then I expect its use to rise in those three conditions.

What’s your advice for patients seeking a pharmacogenomic route to treatment?

Once you have the data, there are good resources for patients and providers about what to do with the information. But ultimately you have to work with your health care provider on using the data to tailor your prescriptions.

Sources:

  1. ADEs and older adults: Lown Institute (2018). “Medication overload and older Americans
  2. Increase in ADEs with increase in medications: Department of Health & Human Services’ Patient Safety Network (2019). “Medication Errors and Adverse Drug Events
  3. Info on ER visits, hospitalizations, patients affected by ADEs: Department of Health & Human Services’ Patient Safety Network (2019). “Medication Errors and Adverse Drug Events
  4. 50% of patients not taking drug correctly: Mayo Clinic Proceedings (2011). “Medication adherence: WHO cares?
  5. 30% to 80% of psychiatric patients abandoning treatment: The Westchester Psychiatrist (2016). “Implementing Pharmacogenetic Testing in Psychiatry
  6. Drugs and pharmacogenetic associations: U.S. Food & Drug Administration (2021). “Table of Pharmacogenetic Associations
  7. Percentage of people that have a genetic variation that leads to gene-drug interactions: Vanderbilt University Reporter (2021). “Study shows gene-drug interactions are common
  8. Relationship between genes and drugs not all bad: Future Medicine (2018). “Pharmacogenetic tests and depressive symptom remission: a meta-analysis of randomized controlled trials

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