Considering that nearly 40% of seniors in the U.S. are taking five or more medications, the usefulness of drug metabolizing gene data needs to be positioned appropriately in the context of multi-drug interactions that can impact the phenotype or expression of the gene variants.
The Institute for Health Improvement advocates that “older adults in the US deserve safe, effective, and patient-centered care in the settings in which they receive their care.” IHI and the John A. Hartford Foundation’s Age-Friendly Health Systems initiative has identified a framework of four core elements for success:
1. What Matters: Understand and actively support what matters to older adults
2. Mobility: Review mobility plans for each patient
3. Medications: Discuss whether medications are unnecessary or potentially harmful
4. Mentation: Improve mentation by addressing problems like dementia, delirium, and depression
Precision Pharmacotherapy, presupposes that prior to a medication being dispensed, either the prescriber or the pharmacist assesses necessity of and risk posed by the addition to the patient’s medication regimen. Looking further, one can discern that all four constructs above apply to Precision Pharmacotherapy.
Using these core elements in the context of prescribing a new medication for an older adult, it becomes clear that pharmacogenomics is only one aspect of the precision pharmacotherapy process. Before / in addition to pharmacogenomics testing, the following should be considered:
1. What matters–How will this new medication affect this particular patient’s goals of care (e.g., to go fishing with my grandson or to walk two blocks to the post office)?
2. Mobility–Will this new prescription put the patient at higher risk for falling, especially considering the other medications the patient is taking?
3. Medication—How will stopping a medication impact other medications that compete for gene metabolism (competitive inhibition)? That is, could unintentional overdose result from abrupt discontinuation of a particular medication? Or, is the current medication metabolism balance so fragile that adding another medication (e.g., an OTC) might be problematic?
4. Mentation—Does this new prescription have sedative, anticholinergic or other properties that can impact the brain; does this new medication become additive to the current medication regimen to trigger risk for falls, dementia, or worse?
Pharmacogenomics Testing
Considerations about accumulative medication risk and drug-drug-gene interactions at the point of prescribing are critical to patient safety – and we have not mentioned the usefulness of a pharmacogenomic panel for further personalization of an individual’s medication regimen.
Dr. Arthur L. Kaplan, founding head of the Division of Medical Ethics at NYU School of Medicine in New York City, spoke during a 2002 American Pharmacists Association Annual Conference in Philadelphia about the ethical aspects of our ‘near-future’ ability to understand a person’s health risks, including their drug metabolizing genes. It was overwhelming to consider the decades of trial and error prescribing, and potential improvements that could have resulted from simply knowing if someone were a normal (extensive), partial, ultra, or non-metabolizer based on the absence or presence of metabolizing genes. Yet, while the cost of testing has come down considerably and these tests need only be performed one time, few healthcare professionals have precision prescribing on their radar. Consequently, trial and error prescribing continues to prevail in the U.S.
Some challenges to implementing precision pharmacotherapy include the lack of education of physicians and other prescribers in this vast area of science that likely was non-existent when they attended medical school and is still not a part of the curriculum today. Training on the importance of using pharmacogenomic data or, perhaps even more significant, the importance of multi-drug and drug-gene interactions, seems to occur only in areas such as HIV/AIDS and oncology.
Another challenge is the interpretation, clinical application, and secure electronic storage of pharmacogenomics information for future point-of-prescribing retrieval. Perhaps consumers should be empowered to 1) access and ‘own’ their pharmacogenomics information; 2) become more versed in medication safety issues within their own regimens; and 3) connect with pharmacists who are versed in the science of competitive inhibition. Consumers are typically well aware of their own allergy risks. Similarly, they could become experts in their own medication risks.
Precision Prescribing outcomes
In 2009, Tabula Rasa HealthCare launched a regional local pharmacogenomics initiative to help cardiologists more safely prescribe the anti-platelet drug clopidogrel, a pro-drug requiring CYP2C19 gene metabolism. Despite our efforts to assure that this medication was only being prescribed to patients who could achieve benefit from it, cardiologists were reluctant, as they felt that being on the ‘cutting edge’ with pharmacogenomics could isolate them as ‘outliers’ (that is, if they began ordering PGx kits outside of practice guidelines).
TRHC’s novel medication safety technology, now used in the MedWise Advisor platform, identifies the accumulative risk of medications, along with the affinity coefficients for medication, giving pharmacists an easy way to manage multi-drug interactions. This technology enables pharmacists to quickly make recommendations including:
• separating time-of-day administration so drugs to be metabolized separately avoiding competitive-inhibition
• alternative medications that have different gene metabolizing pathways
• monitoring for potential unintentional aggregate medication side effects, lack of efficacy or unintentional overdose.
When pharmacogenomics test data is available, this technology stores and calculates that data as well, so that healthcare professionals can make even safer, more personalized decisions, at the point of prescribing.
In April, 2018, the results of an implementation of a pharmacist-led pharmacogenomics service in an at-risk, frail elderly population was published. Findings included that the service was feasible and that pharmacists and prescribers can effectively collaborate to integrate pharmacogenomic and multi-drug interaction information into patient care.1 The authors identified that a major finding in the patient sample was that three out of four had at least one major drug-gene interaction.
Conclusion
Technological advancements have eliminated the need for trial-and-error prescribing. Today, there is a plethora of data available from which more informed prescribing decisions can (and ought) be made. Further, aggregation and interpretation of this data has been automated, enabling immeasurably safer point-of-care prescribing. Hospitals and healthcare systems can be the vanguard of Precision Prescribing by asking their EHR vendors for solutions that provide clinical decision support for multi-drug interactions and drug-gene interactions, at the point of care. Pharmacists can support prescribers by making recommendations that improve safety, optimize medication regimens and demonstrate outcomes.
Orsula V. Knowlton, PharmD, MBA, is the president, chief marketing officer and co-founder of Tabula Rasa HealthCare, a healthcare company that provides patient-specific, data-driven technology and services to improve patient outcomes, lower costs, and manage risk. Dr. Knowlton has published widely, and co-authored the first published consensus guidelines on the standards for anticoagulation management centers, in conjunction with the Anticoagulation Forum.
