Chapter e7: Clinical Pharmacogenomics

KEY CONCEPTS

• Genetic variation contributes to pharmacokinetic and pharmacodynamic properties of medications.

• Genetic variation affects drug-metabolizing enzymes, transporters, and target proteins, as well as immune-related proteins that may impact medication response.

• Genetic polymorphisms may influence medication effectiveness and risk for toxicity.

• Pharmacogenomics is the study of the impact of genetic polymorphisms on medication response.

• The goals of pharmacogenomics are to optimize medication efficacy and limit toxicity based on an individual’s DNA.

• Single nucleotide polymorphisms are the most common gene variations associated with medication response.

• Evidence-based resources, such as US Food and Drug Administration medication labels, Clinical Pharmacogenetics Implementation Consortium Guidelines, and the Pharmacogenomics Knowledgebase, are available to help clinicians select and dose medications based on a patient’s genetic profile.

• The pharmacist plays a key role in advancing pharmacogenomics in clinical practice as part of a multidisciplinary healthcare team.

Patient Care Process for Application of Pharmacogenomics

Collect

• Patient characteristics (eg, age, sex, pregnancy)

• Patient medical history (personal and family)

• Current medications including OTC use, herbal products, dietary supplements

• Pharmacogenomic test results that are relevant to a patient’s care (eg, CYP2C19 genotype if the patient is being considered for clopidogrel therapy)

Assess

• Pharmacogenomic test results, including translating genotype to phenotype to drug therapy recommendation (see Tables e7-4, e7-6, and e7-7)

• Impact of genetic variation on pharmacokinetics and/or pharmacodynamics (see Fig. e7-3)

• Medication-related problems that may be related to genetic variability, even when a pharmacogenomic test has not been done

• Disease implications of pharmacogenomic test results and refer the patient to a genetics-trained healthcare provider when necessary

• Predisposition to disease and drug response

• Quality and source of existing pharmacogenomic test results

• Actionable versus non-actionable pharmacogenomic test results using high quality, evidence-based pharmacogenomics databases, and clinical guidelines (see Table e7-8)

• Cost, cost-effectiveness, and reimbursement issues relevant to pharmacogenomic tests and services

Plan^*

• Integrate pharmacogenomic test results with other clinical variables to optimize medication therapy (see Fig. e7-6)

• Recommend pharmacogenomic testing when appropriate.

Implement^*

• Pharmacogenomics-guided care plan

• Document pharmacogenomic test results in the electronic health record

Follow-Up: Monitor and Evaluate

• Presence of medication-related adverse effects

• Pharmacogenomics-guided care plan

BEYOND THE BOOK

Visit the CPIC Website: https://cpicpgx.org/. Select and review a gene-drug guideline. Briefly describe how these recommendations may be applied to clinical practice. This activity is intended to build your experience with accessing pharmacogenomic guidelines and how they may be integrated into prescribing decisions.