CPIC Recommendations
| Phenotype / Drug* | Implication | Therapeutic recommendation | Classification of recommendation |
|---|---|---|---|
| CYP2C19 Poor Metabolizer Clopidogrel |
Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events. | Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication. | ACS and/or PCI: Strong -ACS, acute coronary syndrome; PCI, percutaneous coronary intervention. Non- ACS, non-PCI cardiovascular indications: Moderate - Non-ACS, non-PCI cardiovascular indications include peripheral arterial disease and stable coronary artery disease following a recent myocardial infarction outside the setting of PCI. |
| CYP2C19 Poor Metabolizer Sertraline |
Greatly reduced metabolism when compared to extensive metabolizers. Higher plasma concentrations may increase the probability of side effects. | Consider a 50% reduction of recommended starting dose and titrate to response or select alternative drug not predominantly metabolized by CYP2C19. Drug-drug interactions and other patient characteristics (e.g., age, renal function, liver function) should be considered when selecting an alternative therapy. |
Optional |
| CYP2D6 Ultra-rapid Metabolizer Codeine |
Increased formation of morphine leading to higher risk of toxicity. |
Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid. | Strong |
| CYP2D6 Ultra-rapid Metabolizer Doxepin |
Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure. |
Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. |
Optional |
| CYP2D6 Ultra-rapid Metabolizer Clomipramine |
Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure. |
Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments. |
Optional |
| CYP2D6 Ultra-rapid Metabolizer Tramadol |
Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity. |
Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid. |
Strong |
| TPMT Poor Metabolizer Mercaptopurine |
Extremely high concentrations of TGN (thioguanine nucleotides) metabolites; fatal toxicity possible without dose decrease; no MeTIMP metabolites. Greatly increased risk of thiopurine related leukopenia, neutropenia, myelosuppression. |
For malignancy, start with drastically reduced doses (reduce daily dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g., 10 mg/m2/day given just 3 days/week) and adjust doses of mercaptopurine based on degree of myelosuppression and disease-specific guidelines. Allow 4–6 weeks to reach steady-state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignant conditions, consider alternative non-thiopurine immunosuppressant therapy. |
Strong |
* Please find the recommendation for particular drug, you are going to prescribe, from the list.