Remember wondering: When will I ever use pharmacokinetic/pharmacodynamic (PK/PD) modeling? Recall constant musing over: How will I keep my patients loyal to me? Or, how can I have a new revenue stream that ties into my professional license?
Well, enter personalized and precision pharmacotherapy.
When I started my community pharmacy (at a time when you could not put the name of the medication on the Rx label), prescribing was done mostly by “preference.” When computers entered our community practices in the 70s and 80s, university-types learned they could harvest data and start applying it to what came to be known as “population-based or evidence-based” prescribing. In 2011, Larry Lesko, Ph.D., who was in charge of pharmacology for the Food and Drug Administration, started a rumor, which conveyed the notion that it was time to enhance preference and evidence-based prescribing with “personalized” and even “precision” prescribing.
What does that mean for you?
When you think about it, most patients believe that all prescriptions are written and dispensed from a “personalized” perspective. In other words, “the prescriber and pharmacists tailored the medication for me!” However, we know that the reality is that the patient’s prescription is primarily based on the patient’s condition, the corresponding standard of care, and formulary constraints. We also recognize there are many confounding pharmacotherapy variables that affect medication use, such as: patients are genetically different from one another, patients take different combinations of medications, patients take their medications at different times of the day, patients have different liver and kidney function, patients take medications with or without food, patients swallow medications with liquid other than water, as well as other demographic factors such as gender and age. Furthermore, we know that the incidence of Adverse Drug Events (ADEs) increases, especially with older patients who take many prescription medications, over-the-counter (OTC) medications, dietary supplements, recreational medications, samples, etc.
The Pandemic of ADEs
The literature shows us that older people taking five or more meds have a 50% chance of an annual ADE, while this increases for those taking eight or more medications to 81%. The Centers for Disease Control cites data that 39% of US people (i.e., about 20 million over age 65) take five or more meds daily. This data only reflects prescription meds. If they were able to include non-prescription medication, the data would be even more impactful. The literature also shows that 6% of hospitalized patients in the US have an ADE in the hospital that results in doubling the length of stay. If ADEs were a disease, it would be the fourth-leading cause of death in the US.
Certainly, the ubiquitous nature of ADEs is not the prescriber’s or pharmacist’s fault. The medication decision support software in pharmacies and in EHRs is about 40 years old. It looks at one-drug to one-drug interactions, and only denotes that when drug A is taken with drug B, side effect or adverse event C may happen.
Personalized Pharmacotherapy (A Better Way)
Personalized pharmacotherapy involves the application of PD and PK at point of care – before processing a prescription.
Pharmacodynamics – or, what medications do to the body.
For instance, instead of using “May Cause Drowsiness” stickers, one can quantify the aggregated sedative burden of a patient’s particular medication and their medication regimen as a whole. Likewise, this type of assessment can be made for other potential medication-related burdens, such as anticholinergic effects and risk of corrected QT interval (QTc) prolongation. It is essential to evaluate each new medication for its pharmacodynamic properties; however, it can be significant to evaluate the impact each new medication has on the overall risk of medication-related adverse effects.
Pharmacokinetics – or, what the body does to medications.
Medications are poisons. Of our 30,000 genes, a couple hundred genes are there to encode proteins to water-solubilize poisons, including medications, so they can be excreted. To dig a bit deeper, a patient’s genotype has four properties of interest to us:
- To activate pro-drugs (about 7% of meds are pro-drugs)
- To eliminate most drugs (some are already water-soluble or are eliminated by other means)
- To transport drugs around the body
- To affect the desired purpose of the medication (e.g., receptors).
All four of these activities are dependent upon genes inherited from our parents, grandparents, etc. If we do a cheek swab and have a pharmacogenomic (PGx) test done, then we know which genes are considered normal and which display a variant. With the PGx test, we can easily discern which drug-gene pairs will act normally and which will not metabolize normally. There are five general descriptors of how these genes will display their effect on metabolism for drug-gene pairing:
- Normal: One functioning allele from each parent
- Intermediate: One functioning allele and one non-functioning allele
- Poor: Neither allele is functioning
- Rapid: One functioning allele and multiple copies of the other allele
- Ultra-rapid: Multiple copies of each allele
In addition to drug-gene pair, there is another side to this story. Often our patients are taking multiple medications. If, for instance, two or three medications that seek the same gene for activation, elimination, transporting, or receptor action are taken at the same time, then the notion of competitive inhibition arises. The medication with the highest affinity to the gene (think of the gene as a parking space in the gut and liver) will first occupy the parking spaces, while the other medications will continue to circulate around the body in the form they were originally administered (e.g., inactive for pro-drugs and active for others) – setting the stage for an ADE.
Precision Pharmacotherapy (The Best Way)
The difference between Personalized PK and Precision PK is applying the PGx information. When the results from the PGx test are in front of you, you have Precision Pharmacotherapy – for both drug-gene pairs and for competitive inhibition.
Medication Risk Score
All of this information – PD/PK/PGx – is instantaneously available to you in one screen, using software called MedWise Advisor®. MedWise Advisor is a web-accessible platform based on Tabula Rasa HealthCare’s proprietary technology for predicting the medication safety risk of a medication regimen. MedWise Advisor translates the PD, PK, and optionally the PGx, associated with a patient’s medication regimen to formulate meaningful and actionable views of each risk. Incorporating all of this data also provides you with a calculated Medication Risk Score from 0 to 50, wherein a score of 12 or more indicates that medication risk for ADEs ought to be mitigated.
Can you envision a sign in your practice that says something like this to your patients? You know your FICO Credit Risk Score. Would you like to know your Medication Risk Score? Join our Concierge Medication Safety program to know your Medication Risk Score and how we will help you manage it.
The Good News
QS/1 and Tabula Rasa HealthCare have teamed up to integrate MedWise Advisor into QS/1. Stay tuned! We will be in beta testing with a handful of pharmacies by Q4 this year, with anticipated full launch in 2019. We firmly believe that this medication risk identification and mitigation system, which has been in use for over four years by hundreds of pharmacists, will not only help you optimize your patients’ regimens and time-of-day administration, it will provide velcro for patient loyalty. In addition, Concierge Medication Safety is a stand-alone offering, independent of prescription dispensing, which should be offered by you as a subscription service on a monthly/yearly basis.
More information will be forthcoming toward the end of this year.