How to discuss pharmacogenetic test results with your patients: a guide for pharmacists and prescribers

Pharmacogenetic (PGx) testing is now offered in many community pharmacies and clinics, and more patients arrive with a report in hand. The test itself is simple: a cheek swab. When results are used well, they make a difference: in the large European PREPARE study, using a 12-gene pharmacogenetic panel to guide prescribing reduced clinically important side effects by about 30%. The conversation around it is where most of the value, and most of the risk, lies. A patient who misreads a result may stop a medication that is working, or trust a medication too much. This guide summarizes practical points for pharmacists and prescribers on how to discuss pharmacogenetic testing with patients, before and after the test.

What should patients know before the test?

Pre-test education sets realistic expectations and prevents most misunderstandings later. Cover these points:

• What the test looks at. A pharmacogenetic test reads variants in genes that affect how the body absorbs, activates, breaks down or responds to medications, such as CYP2D6, CYP2C19 and CYP2C9. These genes code for cytochrome P450 (CYP) enzymes, found mainly in the liver, which process more than 70% of all medications in clinical use.
• What it does not do. It does not diagnose disease or predict the risk of conditions such as cancer or dementia. It is about medications only.
• Genes are one piece of the puzzle. Age, kidney and liver function, other medications, smoking, alcohol, pregnancy and illness also affect how a medication works.
• Results last a lifetime. The DNA result does not change, so the test does not need to be repeated, but its interpretation may be updated as guidelines change.
• What happens next. Explain who will review the results, how recommendations will reach the prescriber and that no medication should be changed without talking to them first.

How do you explain metabolizer results in plain words?

Use the standard terms agreed by the Clinical Pharmacogenetics Implementation Consortium (CPIC), so that the patient, the pharmacist and the prescriber all mean the same thing. For enzymes that break down medications, the terms are poor, intermediate, normal, rapid and ultrarapid metabolizer. A simple way to explain them:

• Poor or intermediate metabolizer: "Your body breaks down some medications more slowly than usual. A standard dose can build up and cause side effects, so a lower dose or a different medication may suit you better."
• Normal metabolizer: "Your body breaks down this medication as expected, so the usual dosing and precautions apply."
• Rapid or ultrarapid metabolizer: "Your body clears some medications faster than usual, so a standard dose may not work well enough."

Two cautions help avoid confusion. First, some medications are prodrugs that must be activated by an enzyme. Codeine, for example, is turned into morphine by CYP2D6, so a poor metabolizer may get little pain relief, while an ultrarapid metabolizer can make too much morphine. Clopidogrel needs CYP2C19 to work, so poor metabolizers may get less protection from blood clots. Second, a "normal" result does not guarantee that a medication will work or be free of side effects. It means there is no genetic reason to change the usual approach.

Why must results be reviewed with the current medication list?

A gene result read on its own can be misleading. Other medications can block or speed up the same enzymes, a change called phenoconversion. Fluoxetine, paroxetine and bupropion strongly block CYP2D6, so a patient with normal CYP2D6 genes who takes one of them can respond to codeine or tramadol like a poor metabolizer. Smoking speeds up CYP1A2, and inflammation and older age can slow several enzymes. Always interpret pharmacogenetic results together with the full, current medication list, including over-the-counter products and supplements, and review them again when medications change.

How do you close the loop with the prescriber?

Pharmacogenetic testing works best as a team effort. Whoever counsels the patient should make sure that the prescriber receives clear, actionable recommendations, and that the patient knows what will happen next.

• Send specific recommendations, for example a dose adjustment or an alternative medication, with the guideline that supports them.
• Document the result in the pharmacy profile and the patient's chart, using standard metabolizer terms.
• Tell the patient not to stop or change medications on their own. Patients who read a result without counselling may lose confidence in a medication that is working for them.
• Follow up to confirm that the prescriber received the recommendations and to check how the patient is doing after any change.

How do you keep results useful over time?

Pharmacogenetic results are lifelong, but they help only if they are available when the next medication is prescribed. Encourage patients to keep their report accessible, for example on their phone, and to share it with every prescriber, pharmacist and hospital team. Guidelines also change: in 2020, CPIC and the Dutch Pharmacogenetics Working Group (DPWG) agreed on a new way to translate CYP2D6 results, and some patients were reclassified from normal to intermediate metabolizers. Choose a testing provider that updates reports as guidelines change. Read more about why pharmacogenetic results must stay up to date and follow the patient.

Where can you find trusted pharmacogenetic guidance?

• CPIC guidelines give gene-drug recommendations graded by strength of evidence, now hosted on ClinPGx (formerly PharmGKB).
• DPWG guidelines from the Royal Dutch Pharmacists Association cover many of the same gene-drug pairs and are also summarized on ClinPGx.
• Health Canada product monographs, searchable in the Drug Product Database, include pharmacogenetic information for some medications.

For more on how prescribers use these tests, read pharmacogenetic tests as a decision support tool for prescribers.

How can a Pillcheck test help?

With Pillcheck, a pharmacist reviews each patient's results together with all of their current medications, accounts for drug-drug-gene interactions and prepares recommendations based on current pharmacogenetic guidelines and drug labels, ready to share with the prescriber. Pillcheck notifies patients when an updated report is posted, so the interpretation stays current without a new test.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• Before the test, explain that it looks at how genes affect medications, does not diagnose disease and is one factor among many.
• Use the standard CPIC metabolizer terms and plain-language explanations, and explain that a "normal" result is not a guarantee.
• Always review results together with the current medication list to account for drug-drug-gene interactions.
• Close the loop: send specific recommendations to the prescriber, document them and tell patients not to change medications on their own.
• Keep results accessible and up to date, and use CPIC, DPWG and Health Canada resources.

Frequently asked questions

Can a pharmacogenetic test tell a patient which medication will work?

Not on its own. It shows how genes may affect the way the body handles a medication, which helps choose a medication and dose. Diagnosis, other medications and health conditions still matter.

Should patients change their medications after reading their report?

No. Patients should discuss their results with their pharmacist and prescriber, and any change should be made together with them.

What is phenoconversion?

Phenoconversion is a mismatch between the metabolizer status predicted by genes and the actual activity of an enzyme, caused by other medications, smoking, inflammation or age. It is why results must be reviewed with the current medication list.

Do pharmacogenetic results need to be repeated?

No. The DNA result lasts a lifetime. The interpretation should be updated when guidelines change and reviewed when medications change.

References

Caudle KE, Dunnenberger HM, Freimuth RR, et al. Standardizing terms for clinical pharmacogenetic test results: consensus terms from the Clinical Pharmacogenetics Implementation Consortium (CPIC). Genet Med. 2017;19(2):215-223.

Zanger UM, Schwab M. Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther. 2013;138(1):103-141.

Klomp SD, Manson ML, Guchelaar HJ, Swen JJ. Phenoconversion of cytochrome P450 metabolism: a systematic review. J Clin Med. 2020;9(9):2890.

Caudle KE, Sangkuhl K, Whirl-Carrillo M, et al. Standardizing CYP2D6 genotype to phenotype translation: consensus recommendations from the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group. Clin Transl Sci. 2020;13(1):116-124.

Swen JJ, van der Wouden CH, Manson LE, et al. A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study. Lancet. 2023;401(10374):347-356.

Santoso Bentley O. How to discuss pharmacogenetics with your patients. Pharmacy Times. November 2016.