CYP2C19 – Metabolizing medications

The CYP2C19 gene is important in how your body responds to medications and breaks down toxins. Important here is that variants in CYP2C19 impact your individual response to medications such as prilosec, Plavix, valium, and certain SSRIs.

The CYP family of enzymes breaks down both toxins and medications.  (Learn more about other detoxification genes.)

CYP2C19: From Prilosec to Plavix

Talk with your doctor or pharmacist before making any changes to a medication that you are currently taking.

 

The CYP2C19 enzyme is responsible for the breakdown (also called metabolism) of several popular drugs including proton pump inhibitors (Prilosec, Nexium, Prevacid), certain anti-epileptics, and an antiplatelet drug (Plavix).

Several important CYP2C19 genetic variants impact how drugs break down, causing some people to be poor metabolizers and others to be fast metabolizers.

You can have increased side effects (depending on the medication) either from being a slow metabolizer or a fast metabolizer.

Some medications, called pro-drugs, need to break down into their metabolites for the drug to be effective. Other drugs clear your system through the use of the CYP enzymes. Thus, the effect of a variant depends on the specific medication.

CYP2C19 medication examples:

Examples of interactions with CYP2C19 genetic variants:

  • A CYP2C19 fast metabolizer taking omeprazole (Prilosec) to treat h. pylori may have an insufficient response because the drug may not remain active in the body long enough.[ref]
  • Alternatively, pro-drugs, such as Plavix, convert into their active drug state through CYP2C19. If you are a poor metabolizer, it could mean Plavix (an anticoagulant) isn’t activated enough and you wouldn’t be protected from blood clots.[ref]
  • Valium (diazepam) is another common drug metabolized in part by CYP2C19 (along with the CYP3A4 enzyme). Currently, there are no official recommendations to physicians as to reducing the dosages for poor metabolizers, but there is a box warning about CYP2C19.[ref]
  • A couple of SSRI’s, Celexa (citalopram), Zoloft (sertraline), and Lexapro (escitalopram), also metabolize mainly through CYP2C19.[ref]
  • A 2021 study showed that the average dose of citalopram (Celexa) is not as effective as an antidepressant for people with one copy of a non-functioning CYP2C19 variant (rs4244285). [ref]

CYP2C19 Poor Metabolizers:

Check your genetic data below to see if you are likely to be a poor metabolizer. A wide variation exists in how this gene metabolizes these drugs.

  • Approximately 10 – 20% of Asians are poor metabolizers, as are 2 – 5% of people of Caucasian descent.
  • Up to 20-30% of Caucasians are fast metabolizers, but less than 5% of Asians are.

Here is more information on drugs that are metabolized through CYP2C19.

In addition to drug metabolism, CYP2C19 also helps to activate and break down some hormones such as progesterone.[ref]  It is involved (minor) in metabolizing melatonin[ref] and is also involved in the metabolism of estradiol.[ref]  Note that CYP2C19 is not the only route for metabolizing these hormones, just one way that the body can break them down.


Genetic variants that impact CYP2C19:


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CYP2C19 Poor metabolizers:

Check your genetic variants for rs4244285 681G>A (23andMe v4, v5):

  •  A/A: non-functioning (CYP2C19*2)
  •  A/G: poorer metabolizer
  •  G/G: typical[ref]

Members: Your genotype for rs4244285 is .

 

Check your genetic variants for rs4986893 (23andMe v4, v5; AncestryDNA):

  •  A/A: poor metabolizer (CYP2C19*3), increased risk of lung cancer[ref]
  •  A/G: slow metabolizer
  •  G/G: typical[ref]

Members: Your genotype for rs4986893 is .


CYP2C19 Ultra-fast metabolizers:

Check your genetic variants for rs12248560 (23andMe v4, v5; AncestryDNA):

  •  C/C: typical
  •  C/T: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment
  •  T/T: ultrafast metabolizer (CYP2C19*17), more likely to benefit from tamoxifen treatment[ref]

Members: Your genotype for rs12248560 is .

 


Lifehacks:

Lifestyle interactions:

Stop smoking! If you are a CYP2C19 poor metabolizer and a smoker, you are at a 5x increased risk of lung cancer[ref] and a 17x increased risk of laryngeal cancer.[ref]

Interactions with supplements:

The metabolism of D-limonene, a component of citrus essential oils, also occurs through CYP2C19.  If you are a poor metabolizer and taking a medication metabolized through CYP2C19, you may not want to take supplements or essential oils with d-limonene at the same time as the medication.

Inhibitors of CYP2C19 may also interfere with the medications that you are taking.  Common supplements such as quercetin, berberine, and caffeic acid can inhibit CYP2C19.[ref][ref]

Inducers of CYP2C19 include low-dose aspirin.[ref]

Pharmacogenetic testing for antidepressants:

If you are trying to figure out whether an antidepressant will work for you, I would suggest going beyond what you can learn from your genetic raw data file, which may not cover everything.  Instead, look into pharmacogenetic testing, which is a clinical test specifically looking for gene-drug interactions. Your doctor can likely order it for you, or you can order on your own from some testing places.


Related Articles and Topics:

CYP2A6: Breaking down nicotine 
How many cigarettes a day a person smokes – and how hard it is for them to quit – is at least partly dependent on the CYP2A6 gene. This enzyme also metabolizes several important cancer drugs.

CYP2C9: Breaking down prescription medications
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body. Learn how the CYP2C9 variants impact quite a few prescription medications.

CYP3A4: Breaking down prescription meds
Our bodies break down (metabolize) drugs and other toxins through a group of enzymes known as the CYP450 family. Different CYP enzymes break down different substances, and we all carry genetic variants that can impact whether we metabolize a drug quickly or slowly. The CYP3A family of genes is involved in metabolizing about half of the drugs on the market today. Check your genes to see if you carry variants that impact the speed at which you metabolize medications.

Phase I and Phase II detoxification
Learn how the different genetic variants in the phase I and phase II detoxification genes impact the way that you react to medications and break down different toxins.

Originally published July, 2018. Updated Feb. 2021.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering from Colorado School of Mines. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.