Reading pharmacogenomics right

The genotype says "normal". The patient still does not respond.

A gene can be read correctly and still mislead. When a concomitant drug blocks the enzyme, the genotype does not change, but the patient now behaves like a poor metabolizer. This is called phenoconversion.

Prepared by the BIODECODE science team · Last updated: October 2026 · Based on CPIC, DPWG, FDA and peer-reviewed publications

In brief

  • Genotype is the genetic make-up a person is born with, and it never changes. Phenotype is how an enzyme actually works at a given moment.
  • Another drug can suppress or speed up the enzyme. A person with a "normal" genotype may then behave like, for example, a poor metabolizer. This is called phenoconversion.
  • A pharmacogenomic result should therefore always be read together with the patient's current list of medicines.

Key concepts

Genotype

The genetic information a person is born with. It is measured once and does not change.

Phenotype

The real working speed of the enzyme at that moment. It can change with concomitant drugs, illness and age.

Inhibitor

A drug that suppresses an enzyme. A strong inhibitor can almost shut down a normally working enzyme.

Inducer

A drug that speeds an enzyme up. Rifampicin, for example, markedly accelerates some enzymes.

An analogy: the road and the traffic

  1. Genotype is how many lanes the road has

    Genes build the enzyme's "road". A four-lane road is like being born a normal metabolizer.

  2. A second drug is an accident blocking the road

    A strong inhibitor stops the traffic without changing the number of lanes.

  3. The result is today's traffic

    The road still has four lanes, so the genotype has not changed, but nothing moves. The patient behaves like a poor metabolizer.

Common examples of phenoconversion in practice

SituationWhat happens?Clinical relevance
Strong CYP2D6 inhibitor (fluoxetine, paroxetine, bupropion)A normal metabolizer may behave like a poor one.Codeine and tramadol may stop working; tamoxifen's active product may fall.
Strong CYP2C19 inhibitor (fluconazole, fluvoxamine)CYP2C19 activity falls markedly.Levels of drugs processed by CYP2C19 may change.
Clopidogrel with omeprazole or esomeprazoleCYP2C19 is suppressed; clopidogrel is activated less.The FDA has advised avoiding this combination.

Examples are based on FDA drug interaction tables and prescribing information. The size of each interaction varies from person to person.

Who is it relevant for?

  • People taking five or more medicines, especially older adults
  • Patients taking psychiatric and non-psychiatric drugs at the same time
  • Patients with breast cancer taking tamoxifen together with an antidepressant
  • Patients who do not get the expected effect despite a "normal" genetic result

Your physician decides whether the test is right for you.

Evidence

  • Genotype

    Does not change over a lifetime; measured once

    Core principle
  • Phenotype

    Can change with concomitant drugs, organ function and clinical state

    Core principle
  • CYP2D6

    Fluoxetine, paroxetine and bupropion are strong CYP2D6 inhibitors and can make a normal metabolizer behave like a poor one

    FDA drug interaction tables
  • CYP2C19

    Fluconazole and fluvoxamine are among strong CYP2C19 inhibitors

    FDA drug interaction tables

Related genes and drugs

GeneRoleRelated drugsSource
CYP2D6The enzyme most often phenoconverted by strong inhibitorsStrong inhibitor examples: fluoxetine, paroxetine, bupropionFDA
CYP2C19Enzyme that can be suppressed by some antifungals and antidepressantsStrong inhibitor examples: fluconazole, fluvoxamineFDA

What you will see in the BIODECODE report

  • Separate warning

    Concomitant drugs that may change a genotype-based verdict are flagged in the report.

  • Authority differences

    Where CPIC, DPWG and FDA differ, all three are shown side by side.

  • No call

    The status and reason for every locus without a result is written; it is not treated as "normal".

  • Single source

    Verdicts come from a version-controlled knowledge base, with source text.

Sample report (PDF)

Good to know

  • The effect of phenoconversion varies from person to person; the same drug does not suppress the enzyme equally in everyone.
  • Conditions such as severe infection and inflammation can also temporarily reduce the activity of some enzymes.
  • In some situations, measuring the drug level in blood directly (therapeutic drug monitoring) is the most reliable approach.

Frequently asked questions

Does phenoconversion invalidate the test result?

No. The genotype is correct and does not change, but interpretation must take into account every medicine the patient is taking at the time.

What should I tell my physician?

Share a list of everything you take, including prescription, over-the-counter and herbal products.

Can herbal products cause phenoconversion too?

Yes, some can. St John's wort, for example, speeds up certain enzymes. Tell your physician about any herbal products you take.

References

  1. Shah RR, Smith RL. Addressing phenoconversion: the Achilles' heel of personalized medicine. Br J Clin Pharmacol. 2015.
  2. US Food and Drug Administration (FDA). Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers.
  3. US Food and Drug Administration (FDA). Safety communication on the concomitant use of clopidogrel and omeprazole. 2009.
  4. Goetz MP et al. CPIC guideline for CYP2D6 and tamoxifen therapy. Clin Pharmacol Ther. 2018.

This page is for information only; diagnosis and treatment decisions belong to your physician. Never stop or change a medicine on your own.

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