Pharmacogenetics: Using Genetic Information to Guide Drug Therapy

 


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Am Fam Physician. 2015 Oct 1;92(7):588-595.

  Related editorial: Pharmacogenetic Testing--An Unfulfilled Promise.

Author disclosure: No relevant financial affiliations.

Clinical pharmacogenetics, the use of genetic data to guide drug therapy decisions, is beginning to be used for medications commonly prescribed by family physicians. However, clinicians are largely unfamiliar with principles supporting clinical use of this type of data. For example, genetic variability in the cytochrome P450 2D6 drug metabolizing enzyme can alter the clinical effects of some opioid analgesics (e.g., codeine, tramadol), whereas variability in the CYP2C19 enzyme affects the antiplatelet agent clopidogrel. If testing is performed, patients who are ultrarapid or poor metabolizers of CYP2D6 should avoid codeine use (and possibly tramadol, hydrocodone, and oxycodone) because of the potential for increased toxicity or lack of effectiveness. Patients undergoing percutaneous coronary intervention for acute coronary syndromes who are known to be poor metabolizers of CYP2C19 should consider alternate antiplatelet therapy (e.g., ticagrelor, prasugrel). Some guidelines are available that address appropriate drug therapy changes, and others are in development. Additionally, a number of clinical resources are emerging to support family physicians in the use of pharmacogenetics. When used appropriately, pharmacogenetic testing can be a practical tool to optimize drug therapy and avoid medication adverse effects.

Clinical pharmacogenetics determines whether individual differences in the expression of a protein or enzyme affect the metabolism of a drug. These effects may lead to changes in the levels of active or inactive metabolites, possibly warranting the use of a different drug or dose.1 Family physicians are usually the first resource for patient questions about genetics; however, quick and accurate use of pharmacogenetic data in a clinical environment is challenging.2 Patients have increasing interest in and access to their own genetic information, including pharmacogenetic data from direct-to-consumer genetic testing companies (e.g., 23andMe).3 With pharmacogenetic information on the labels of more than 150 drugs approved by the U.S. Food and Drug Administration (FDA), family physicians should have some knowledge of how to find and apply this information.4  eTable A lists resources for more information.

View/Print Table

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferencesComments

Codeine should be avoided in CYP2D6 ultrarapid metabolizers because of the potential for toxicity.

C

13, 23

Consensus guideline based on observational studies and case reports

Codeine, and possibly tramadol, should be avoided in CYP2D6 poor metabolizers because of possible lack of effectiveness.

C

13, 23

Consensus guideline based on observational studies

In poor CYP2C19 metabolizers who are undergoing percutaneous coronary intervention for acute coronary syndromes, ticagrelor (Brilinta) or prasugrel (Effient) should be considered as an alternative to clopidogrel (Plavix) for antiplatelet therapy.

B

9, 36, 37

Consensus guideline based on observational studies; meta-analyses of observational studies show conflicting results


CYP = cytochrome P450.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferencesComments

Codeine should be avoided in CYP2D6 ultrarapid metabolizers because of the potential for toxicity.

C

13, 23

Consensus guideline based on observational studies and case reports

Codeine, and possibly tramadol, should be avoided in CYP2D6 poor metabolizers because of possible lack of effectiveness.

C

13, 23

Consensus guideline based on observational studies

In poor CYP2C19 metabolizers who are undergoing percutaneous coronary intervention for acute coronary syndromes, ticagrelor (Brilinta) or prasugrel (Effient) should be considered as an alternative to clopidogrel (Plavix) for antiplatelet therapy.

B

9, 36, 37

Consensus guideline based on observational studies; meta-analyses of observational studies show conflicting results


CYP = cytochrome P450.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

View/Print Table

eTable A.

Resources for More Information About Clinical Pharmacogenetics

ResourceComments

American Family PhysicianAFP By Topic

Collection of previously published content related to genetics, including pharmacogenetics

http://www.aafp.org/afp/topicModules/viewTopicModule.htm?topicModuleId=56

American Medical Association

Overview of pharmacogenetics

http://www.ama-assn.org/ama/pub/physician-resources/medical-science/genetics-molecular-medicine/current-topics

The Authors

show all author info

KU-LANG CHANG, MD, is a clinical assistant professor in the Department of Community Health and Family Medicine at the University of Florida College of Medicine in Gainesville....

KRISTIN WEITZEL, PharmD, is a clinical associate professor in the Department of Pharmacotherapy and Translational Research at the University of Florida College of Pharmacy.

SIEGFRIED SCHMIDT, MD, PhD, is a professor in the Department of Community Health and Family Medicine at the University of Florida College of Medicine.

Address correspondence to Ku-Lang Chang, MD, University of Florida, 200 SW 62nd Blvd., Ste. D, Gainesville, FL 32607 (e-mail: changk@shands.ufl.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

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