Cytochrome P450 2C19 (CYP2C19)

PG4KDS Implemented Genes

CYP2C19 is an enzyme that is responsible for breaking down (metabolizing) several of the drugs that are commonly used today. Some medications, such as clopidogrel, require activation by CYP2C19 in order for the medication to be effective. Other drugs, such as tricyclic antidepressants (e.g., voriconazole, amitriptyline and imipramine), are metabolized to forms that are not active and are more easily eliminated from the body. There are many other medications that may be affected by CYP2C19 (see this link: http://www.pharmgkb.org/gene/PA124).

Over 20 known differences exist in the gene for CYP2C19. These differences in the CYP2C19 gene lead to the production of an enzyme that ranges from completely inactive to overactive. A system designed to classify patients into 4 metabolizer categories based on the ability of their CYP2C19 to break down drugs is used by clinicians to help guide drug therapy decisions.

Priority CYP2C19 genotypes

  • Poor metabolizers – These patients have little or no working CYP2C19. About 10 percent of people are poor metabolizers.
    • Drugs we recommend to avoid in some settings:
      • Clopidogrel. Clopidogrel has little to no antiplatelet effect in poor metabolizers of CYP2C19 in these patients in some settings. Other antiplatelet medications (such as prasugrel or ticagrelor) may be recommended.
    • Drugs that may need to be avoided or have their doses decreased:
      • Amitriptyline. Blood levels of amitriptyline are expected to be high in poor metabolizers of CYP2C19, and side effects may be more likely. If amitriptyline is used in these patients, lower doses may be needed. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.
      • Voriconazole. Blood levels of voriconazole are expected to be high in poor metabolizers of CYP2C19, and side effects may be more likely. If voriconazole is used in these patients, lower starting doses may be needed.
    • Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these other drugs.
  • Ultra rapid metabolizers – These patients have greater-than-normal CYP2C19 function. About 17 percent of people are ultra rapid metabolizers of CYP2C19.
    • Drugs we recommend to avoid or have their doses increased:
      • Voriconazole. Blood levels of voriconazole are likely to be low; therefore ultra rapid metabolizers of CYP2C19 may not respond well to this medicine unless higher doses are used. Other antifungal medications may be recommended.
    • Drugs that may need to be avoided:
      • Amitriptyline. Blood levels of amitriptyline are expected to be high in poor metabolizers of CYP2C19, and side effects are likely. If amitriptyline is used these patients, lower doses may be needed. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.
    • Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these drugs.

Routine genotypes. Most CYP2C19 medicines don’t need to be adjusted based on the following genotypes:

  • Intermediate metabolizers – These patients metabolize drugs at a rate somewhere between the poor and extensive metabolizers. About 30 percent of people are intermediate metabolizers.
  • Extensive metabolizer – These patients have normal CYP2C19 function. About 43 percent of people are extensive metabolizers.


More information for patients...

"Do you know..." info sheet: Cytochrome P450 2C19 (CYP2C19) and medicines

More information for healthcare professionals, visit www.pharmGKB.org.

Legal Disclaimer: This page is intended to provide implementers with guidance on establishing a clinical pharmacogenetic program at their institution. Information contained on this page is for information and educational purposes only. Although reasonable efforts have been made to ensure that the information provided on this page is current, complete and, where appropriate, based on scientific evidence, St. Jude Children's Research Hospital makes no assurances as to whether the provided information will at all times be current or complete. St. Jude Children's Research Hospital, in offering this document, is not providing medical advice or offering a consultative opinion, and is not establishing a treatment relationship with any given individual. You, therefore, should not substitute information contained herein for your own professional judgment, nor should you rely on information provided herein in rendering a diagnosis or choosing a course of treatment for a particular individual.