Cytochrome P450 2C19 (CYP2C19)

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 voriconazole and antidepressants (e.g., amitriptyline and sertraline), 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.

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.

Poor metabolizers – These patients have little or no working CYP2C19. About 10 percent of people are poor metabolizers.

• Drugs that may need to be avoided or have their doses decreased:
  
  • Clopidogrel. Clopidogrel has little to no antiplatelet effect in poor metabolizers of CYP2C19. Other antiplatelet medications (such as prasugrel or ticagrelor) may be recommended.
    
  • 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.
  • Sertraline. Blood levels of sertraline are expected to be high in poor metabolizers of CYP2C19, and side effects may be more likely. If sertraline is used in these patients, lower maintenance doses and slower titration in dose may be needed.
  • Escitalopram. Blood levels of escitalopram are expected to be high in poor metabolizers of CYP2C19, and side effects may be more likely. If escitalopram is used in these patients, lower maintenance doses and slower titration in dose may be needed.
  • Citalopram. Blood levels of citalopram are expected to be high in poor metabolizers of CYP2C19, and side effects may be more likely. If citalopram is used in these patients, lower maintenance doses and slower titration in dose may be needed.
• Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these other drugs.

Intermediate metabolizers – These patients metabolize drugs at a rate somewhere between the poor and normal metabolizers. About 30 percent of people are intermediate metabolizers.

• Drugs we recommend to avoid:
  • Clopidogrel. Clopidogrel has little to no antiplatelet effect in intermediate metabolizers of CYP2C19. Other antiplatelet medications (such as prasugrel or ticagrelor) may be recommended.

Rapid metabolizers – These patients have slightly higher CYP2C19 function compared to normal. About 12 percent of people are rapid metabolizers.

• Drugs that may need to be avoided:
  • Amitriptyline. Blood levels of amitriptyline are expected to be low in rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other tricyclic antidepressant medications may be recommended. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.
  • Escitalopram. Blood levels of escitalopram are expected to be low in rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other antidepressant medications may be recommended.
  • Citalopram. Blood levels of escitalopram are expected to be low in rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other antidepressant medications may be recommended.
• Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these drugs.

Ultra-rapid metabolizers – These patients have greater-than-normal CYP2C19 function. About 5 percent of people are ultra-rapid metabolizers of CYP2C19.

• Drugs we recommend to avoid or have their doses increased:
  • Lansoprazole. Blood levels of lansoprazole are likely to be low; therefore, ultra-rapid metabolizers of CYP2C19 may not respond well to this medicine. Consider doubling the starting dose of lansoprazole.
  • Omeprazole. Blood levels of omeprazole are likely to be low; therefore, ultra-rapid metabolizers of CYP2C19 may not respond well to this medicine. Consider doubling the starting dose of omeprazole.
  • Pantoprazole. Blood levels of pantoprazole are likely to be low; therefore, ultra-rapid metabolizers of CYP2C19 may not respond well to this medicine. Consider doubling the starting dose of pantoprazole.
  • 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 (such as posaconazole or amphotericin B) may be recommended.
  • Drugs that may need to be avoided:
    • Amitriptyline. Blood levels of amitriptyline are expected to be low in ultra-rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other tricyclic antidepressant medications may be recommended. Amitriptyline dosing is also affected by the CYP2D6 genotype test result.
    • Escitalopram. Blood levels of escitalopram are expected to be low in ultra-rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other antidepressant medications may be recommended.
    • Citalopram. Blood levels of escitalopram are expected to be low in ultra-rapid metabolizers of CYP2C19, and patients may not respond well to this medicine. Other antidepressant medications may be recommended
  • Other drugs may be affected. The PG4KDS study will evaluate what should be done for the dosing of these drugs.

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

Normal metabolizer – These patients have normal CYP2C19 function. About 43 percent of people are normal metabolizers.