By Briana Skalski, PharmD, BCGP
Clinical Initiatives Pharmacist, AnewHealth
PACE participants often manage multiple chronic conditions and complex medication regimens. That makes medication management central to participant safety, function, quality of life, and long-term outcomes.
It also creates growing urgency around polypharmacy in older adults.
A recent study published in the Journal of the American Geriatrics Society examined medication use among 7,828 adults age 65 and older, drawing on national survey data collected between 1999 and 2016. More than 40% were taking five or more prescription medications, commonly defined as polypharmacy. After researchers accounted for overall health and underlying conditions, taking five or more medications was associated with a 38% increase in overall mortality risk. Each additional prescription medication was associated with a 7% increase in risk.
For PACE organizations, the question is not simply how many medications a participant takes. It is how those medications work together, how the participant responds, and whether the care team has enough insight to intervene before medication-related risk contributes to a fall, treatment failure, adverse event, or avoidable utilization.
Pharmacogenomics, often abbreviated PGx, is the study of how a person’s genes affect their response to medications. In PACE, it can add an important layer of insight to that question.
1 Polypharmacy in PACE Requires More Individualized Medication Management
No two participants respond to medications in exactly the same way.
Age, disease states, renal and hepatic function, adherence, drug interactions, and treatment history can all influence medication response. Genetics may also help explain why one participant experiences toxicity at a low dose while another receives little benefit from the same medication.
Pharmacogenomics examines how genetic variation influences medication metabolism, exposure, treatment response, and the risk of adverse effects. It may help clinicians better understand questions that commonly arise in PACE:
- Why is this participant experiencing adverse effects at an appropriate dose?
- Why is a medication not working despite dose increases?
- Why do side effects persist after other adjustments?
- Could another medication be more appropriate?
PGx does not determine whether a medication will work or cause harm. It gives the care team additional information to consider alongside the participant’s complete clinical picture.
PGx informs decisions. It does not make them.
Why medication count alone does not tell the full story
Medication count can help identify risk, but it does not reveal which therapy is ineffective, poorly tolerated, unnecessary, or interacting with the rest of the regimen.
A participant taking several medications may be stable and receiving meaningful benefit from each. Another taking fewer medications may still face significant risk because of drug interactions, altered metabolism, or cumulative effects.
The opportunity is to move beyond medication count and better understand how the complete regimen is affecting the individual participant.
2 PGx Results Must Be Interpreted Within the Full Medication Regimen
Pharmacogenomic testing may identify whether a participant is a poor, intermediate, normal, rapid, or ultrarapid metabolizer for a particular enzyme. That classification can influence medication exposure, effectiveness, or adverse-effect risk.
The clinical meaning depends on the medication.
For some drugs, slower metabolism may increase exposure and toxicity. For others, it may reduce effectiveness because the medication must first be activated by the body.
Clopidogrel is one example. It must be activated by the CYP2C19 enzyme. A participant who is a CYP2C19 poor metabolizer may produce less active medication, reducing its antiplatelet effect and potentially increasing thrombotic risk.
Codeine and tramadol present a different challenge. Variations in CYP2D6 activity may contribute to either inadequate pain relief or increased exposure to active metabolites.
Other medications commonly encountered in PACE with available PGx guidance include certain antidepressants and antipsychotics, proton pump inhibitors, statins, metoprolol, NSAIDs, azathioprine, and tamoxifen.
What is phenoconversion, and why does it matter in PACE?
Genetics do not operate in isolation. A participant’s medications can change how their genetically predicted metabolism functions in practice, a process known as phenoconversion.
A participant may genetically be classified as a normal metabolizer. If another medication strongly inhibits the same enzyme, that participant may function more like a poor metabolizer. In effect, the interaction can override what the genetic result alone would predict.
This is particularly important in PACE because participants often take multiple prescription medications, over-the-counter products, vitamins, and supplements. Looking only at a drug-gene interaction may miss a more complex drug-drug-gene interaction.
That is why the value of pharmacogenomics extends beyond the laboratory report. Results must be interpreted within the participant’s complete regimen, clinical history, organ function, treatment goals, and current response.
3 PGx Testing Should Lead to Practical Clinical Action
The goal of PGx is not to generate more data for clinicians to review. It is to help explain medication-related challenges and support clearer decisions.
Testing may be considered reactively, after an unexpected response, or preemptively, before starting a medication with established PGx guidance. PACE organizations may also use targeted approaches based on medication classes or clinical risk.
Which PACE participants may be candidates for PGx testing?
Potential candidates may include participants experiencing:
- Multiple medication failures
- Unexpected or persistent adverse effects
- Falls without a clear explanation
- Significant polypharmacy
- Use of medications with established PGx guidance
Once results are available, a PGx-specialized pharmacist can evaluate the genetic findings alongside the participant’s complete regimen and broader clinical context. That analysis may support therapeutic substitution, dose adjustment, enhanced monitoring, avoidance of a medication with reduced expected efficacy, or consideration of deprescribing.
The recommendation is then reviewed with the prescriber and the PACE interdisciplinary team.
Why expert PGx interpretation matters
Pharmacogenomics does not replace clinical judgment. It strengthens it.
PACE clinicians already evaluate medications through the lenses of diagnoses, renal and hepatic function, cognition, falls risk, adherence, participant preferences, and goals of care. PGx adds another lens that may help explain why two participants respond differently to the same therapy.
AnewHealth pharmacists translate those findings into participant-specific, non-directive decision support. The objective is not to tell clinicians what decision to make, but to provide clearer insight into potential risks, alternatives, and next steps.
A test result alone is information. A clinically informed recommendation can help the care team act.
How PGx Supports More Informed Deprescribing
The recent polypharmacy study has renewed attention on deprescribing, the thoughtful reduction or discontinuation of medications that may no longer be necessary, effective, or appropriate.
Pharmacogenomics can support those conversations, but it should not be viewed only as a tool for removing medications.
Testing may show that a participant is unlikely to receive the intended benefit from a medication. It may also identify an alternative therapy, a need for dose adjustment, or a drug-drug-gene interaction contributing to adverse effects.
The objective is not simply fewer medications. It is a safer, more effective, and more individualized regimen.
What PACE Organizations Should Expect From a PGx Pharmacy Partner
As interest in personalized medicine grows, PACE organizations should look beyond whether a pharmacy partner can facilitate testing. The more important question is what happens after the result arrives.
A PGx pharmacy partner should be able to identify appropriate testing opportunities, interpret drug-gene and drug-drug-gene interactions, evaluate findings against the complete regimen, and provide practical clinical guidance to the prescriber and interdisciplinary team.
AnewHealth’s approach brings PGx into the broader medication-management process rather than treating it as a standalone service. Our pharmacists connect genetic insight to the realities of participant care, where every decision must account for clinical complexity, participant goals, and the needs of the PACE team. It is one part of the PACE pharmacy services we provide to organizations nationwide.
Moving Forward: From More Medications to Better Medication Decisions
Polypharmacy will remain a central challenge in caring for medically complex older adults.
The answer is not to assume that every medication is harmful or that every participant taking multiple medications requires genetic testing. It is to create better visibility into which participants may be at risk, why a medication may not be working as expected, and where a more individualized approach could improve care.
When genetic findings are combined with the participant’s complete regimen and interpreted by clinicians who understand PACE, PGx can support earlier risk identification, more informed prescribing, and better decisions around deprescribing, substitution, dose adjustment, and monitoring.
For PACE organizations, that is the opportunity: moving from polypharmacy as a medication count to precision as a clinical strategy. If your organization is exploring what that looks like in practice, our PACE team is glad to talk it through.
Frequently Asked Questions About Pharmacogenomics in PACE
What is pharmacogenomics (PGx)?
Pharmacogenomics, or PGx, is the study of how genetic variation influences a person’s response to medications, including how a drug is metabolized, how much reaches the bloodstream, how well it works, and the likelihood of adverse effects. In PACE, PGx results are used as one input alongside a participant’s full clinical picture rather than as a standalone answer.
How is PGx used in a PACE program?
PGx testing may be used reactively after an unexpected medication response, or preemptively before starting a drug with established PGx guidance. A PGx-specialized pharmacist interprets the result against the participant’s complete regimen and shares practical recommendations, such as therapeutic substitution or dose adjustment, with the prescriber and interdisciplinary team.
Does PGx testing replace clinical judgment?
No. PGx informs decisions but does not make them. A genetic result describes probability, not certainty, and its meaning depends on the specific medication, the rest of the regimen, organ function, and the participant’s goals of care. It adds one more lens to the assessment PACE clinicians already perform.
What is the difference between a drug-gene and a drug-drug-gene interaction?
A drug-gene interaction involves a single medication and a genetic variant that affects how the participant processes it. A drug-drug-gene interaction adds a second medication that changes how that gene’s enzyme functions in practice, a process called phenoconversion. Because PACE participants often take multiple medications plus over-the-counter products and supplements, reviewing only drug-gene pairs can miss the more consequential interaction.
Continue the Conversation With AnewHealth
Learn more about how PGx can support individualized medication management at the 2026 National PACE Association Annual Conference, taking place October 11 to 14 at the Sheraton Denver Downtown in Denver, Colorado.
We also invite PACE leaders to join us for our next Impact & Innovation Summit, November 10 to 12 in Huntington Beach, California, where we will continue exploring how clinical expertise, technology, and deeper pharmacy integration can support the future of PACE.
