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Phenoconversion, explained.

Why one medicine can make a patient handle another medicine as if they had different genes, and why that matters for older adults who take many medicines.

Educational only. This is not medical advice. This page explains a general idea for training and awareness. It does not apply to any one person. Do not start, stop or change any medicine because of this page. Questions about a specific resident or patient belong with their prescriber and pharmacist.

What it is

When genes say one thing and the body does another.

Many medicines are broken down or switched on by enzymes in the liver. Genes help set how well those enzymes work, so a genetic test can predict how a person will handle a drug.

Phenoconversion is the name for a mismatch between that genetic prediction and how the person actually handles drugs, caused by something other than genes[1]. A common cause is another medicine. If a patient takes a drug that blocks a liver enzyme, they can process other drugs that rely on that enzyme as if they had a different genetic type.

Step 1

The genes

A patient's genes predict a normal-working enzyme. On paper, they should handle drugs that use it in the usual way.

Step 2

A second medicine

The patient starts a medicine that strongly blocks that same enzyme.

Step 3

The result

The enzyme now works far less. The patient responds to drugs that depend on it as if they were a poor metabolizer, someone whose enzyme barely works.

An example

CYP2D6, codeine and tramadol.

CYP2D6 is a liver enzyme. Codeine and tramadol need it to turn into the forms that relieve pain: codeine into morphine, and tramadol into a compound called O-desmethyltramadol. The Clinical Pharmacogenetics Implementation Consortium (CPIC), a group that writes guidelines on genes and drug response, says that in poor metabolizers this conversion is greatly reduced, which leads to less pain relief[2].

CPIC also says that a patient's CYP2D6 type can change when they take drugs that block CYP2D6. For patients on a strong CYP2D6 blocker, CPIC treats the predicted type as a poor metabolizer[2]. So a patient whose genes look normal may get little pain relief from codeine or tramadol while also taking a strong CYP2D6 blocker.

The FDA lists examples of drugs that block CYP2D6[3]. Some are common in older adults:

FDA categoryExamples the FDA lists
Strong CYP2D6 inhibitorsbupropion, fluoxetine, paroxetine, quinidine
Moderate CYP2D6 inhibitorsabiraterone, cinacalcet, duloxetine, mirabegron, rolapitant

Partial lists taken from the FDA page cited below[3]. They are examples, not a complete list.

Why it matters

Older adults take more medicines, so there are more chances for a clash.

Federal survey data show that 39.8 percent of U.S. adults aged 65 and over used five or more prescription drugs in the past 30 days in 2015 to 2016[4]. Each added medicine is another chance that one drug changes how the body handles another.

A review of phenoconversion research points out that many patients have several conditions and take several drugs at the same time, while most studies look at one drug or one factor at a time[1]. In practice, this means:

  • A genetic test result is not the whole story. CPIC notes that CYP2D6 type may be altered in a patient who is taking drugs that block CYP2D6[2]. Read any genetic result alongside the current medication list.
  • "This pain medicine does not work" can be a clue. If a resident or patient reports poor relief, a recent new medicine may be part of the reason. Raise it with the prescriber and pharmacist.
  • Medication lists change. A new prescription, a stopped drug or a hospital stay can change the picture. Reviewing the full list after each change helps catch these pairs.
For training

Points to share with your team.

  • Phenoconversion means a patient handles a drug differently from what their genes predict, often because of another drug.
  • CYP2D6 is one well-known example. Codeine and tramadol rely on it to relieve pain.
  • Some common medicines strongly block CYP2D6. The FDA keeps a list of examples.
  • Older adults on many medicines have more chances for this to happen.
  • When in doubt, ask the pharmacist and prescriber. Never change a medicine on your own.

Medication safety is daily work.

Veridence helps nursing facilities keep the medication record survey ready. RXLens helps pharmacies review every claim, every day. Talk with the team that fits you.

Talk to VeridenceTalk to RXLens
Sources

Where these facts come from.

  1. Klomp SD, et al. Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review. J Clin Med 2020;9:2890. mdpi.com
  2. Crews KR, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy. Clin Pharmacol Ther 2021;110(4):888-896. Full text (PMC) and PubMed
  3. U.S. Food and Drug Administration. For Healthcare Professionals: FDA's Examples of Drugs that Interact with CYP Enzymes and Transporter Systems. fda.gov
  4. National Center for Health Statistics. Health, United States, 2018, data table for Figure 14: Prescription drug use in the past 30 days, by number of drugs taken and age. cdc.gov

Educational only. Not medical advice. This page does not replace the judgment of a prescriber or pharmacist who knows the patient.