| Drug (n = 39) | Gene(s) (n = 52) | FDA Table Section Classificationb | CPIC Guideline Classification of Recommendation | CPIC Level | PharmGKB Level | PGx Info on FDA Label | Differences in Use Recommendations in CPIC Guideline(s) and FDA Table |
|---|---|---|---|---|---|---|---|
| Abacavir | HLA-B | Recommendation | Strong | A | 1A | Testing required | None |
| Allopurinol | HLA-B | Potential Impact | Strong | A | 1A | NA | CPIC states contraindicated if HLA-B*5801 positive; FDA states higher risk of adverse reaction |
| Amitriptyline | CYP2C19 | Not included | Optional UM/RM, moderate PM | A | 1A | NA | CPIC recommends avoiding amitriptyline in UMs/RMs/PMs |
| CYP2D6 | PK Only | Strong UM/PM, moderate IM | A | 1A | Actionable PGx | CPIC lists additional gene (CYP2C19) and provides dose guidance in IMs and PMs and avoid in Ums; FDA states alters systemic concentrations | |
| Atomoxetine | CYP2D6 | Recommendation | Strong or moderate depending on AS and children vs adults | A | 1A | Actionable PGx | CPIC provides dose guidance for all phenotypes and indicates potential for adverse reactions and improved efficacy compared with non-PMs; FDA states adverse reaction risk in PMs |
| Azathioprine | TPMT | Recommendation | Strong IM/PM | A | 1A | Testing recommended | CPIC provides dose guidance for IMs and for malignancy in PMs, advises considering alternatives for other PMs; FDA indicates consider alternatives in PM and dose reduction in IM |
| NUDT15 | Recommendation | Strong | A | 1A | Testing recommended | ||
| Capecitabine | DPYD | Recommendation | Strong or moderate depending on AS | A | 1A | Actionable PGx | CPIC provides dose guidance for IMs; FDA indicates insufficient data available for dosing guidance for IMs |
| Carbamazepine | HLA-B | Recommendation | Strong/optional | A | 1A | Testing required | None |
| HLA-A | Potenial impact | Strong/optional | A | 1A | Actionable PGx | CPIC states avoid use if HLA-A*31:01 positive; FDA states consider risk and benefit; CPIC and FDA have different dosing recommendations | |
| Celecoxib | CYP2C9 | Recommendation | Moderate IM (AS of 1) and PM | A | 1A | Actionable PGx | None |
| Citalopram | CYP2C19 | Recommendation | Strong IM, moderate PM/UM | A | 1A | Actionable PGx | FDA recommends maximum dose of 20 mg in PMs; CPIC recommends 50% dose reduction in PMs and alternative therapy in UMs |
| Clomipramine | CYP2D6 | PK Only | Optional | B | 1A | Actionable PGx | CPIC lists additional gene (CYP2C19), provides dose guidance, and suggests alternative therapy in UMs and PMs; FDA states alters systemic concentrations only |
| CYP2C19 | Not included | Optional UM/RM/PM | B | 1A | NA | CPIC provides optional recommendation to avoid tertiary amines in UMs/RMs/PMs | |
| Clopidogrel | CYP2C19 | Recommendation | Strong PM, moderate IM | A | 1A | Actionable PGx | None |
| Codeine | CYP2D6 | Recommendation and potential impact | Strong UM, moderate IM, optional PM | A | 1A | Actionable PGx | CPIC recommends avoiding use in UMs and PMs; FDA states drug contraindicated in children under 12 years of age, regardless of phenotype |
| Desipramine | CYP2D6 | PK Only | Optional | B | 1A | Actionable PGx | CPIC provides dose guidance and suggests alternative therapy in UMs and PMs; FDA states alters systemic concentrations only |
| Dexlansoprazole | CYP2C19 | PK Only | Moderate for RM, NM, and PM | B | 1A | Actionable PGx | CPIC provides optional dosing recommendations for all phenotypes; FDA states IMs and PMs may have higher systemic concentrations |
| Doxepin | CYP2C19 | PK Only | Optional | B | 1A | Actionable PGx | CPIC provides dose guidance; FDA states alters systemic concentrations only |
| CYP2D6 | PK Only | Optional | B | 1A | Actionable PGx | CPIC states alternative therapy in UMs and provides dose guidance in PMs; FDA states alters systemic concentrations only | |
| Efavirenz | CYP2B6 | Potential Impact | Moderate PM/IM | A | 1A | Actionable PGx | CPIC provides dose guidance in IMs and PMs; FDA states higher concentrations and QT prolongation in PMs |
| Escitalopram | CYP2C19 | PK Only | Moderate PM/UM | A | 1A | Actionable PGx | CPIC recommends considering alternative for UMs and dose reduction for PMs; FDA states alters systemic concentrations (drug was 1 of 2 drugs that were subject of FDA warning letter to INOVA Health) |
| Fluorouracil | DPYD | Recommendation | Strong or moderate depending on AS | A | 1A | Actionable PGx | CPIC provides dose guidance for IMs; FDA indicates insufficient data available for dose guidance for IMs |
| Flurbiprofen | CYP2C9 | Recommendation | Moderate IM (AS of 1) and PM | A | 1A | Actionable PGx | None |
| Fluvoxamine | CYP2D6 | PK Only | Optional PM | B | 1A | Actionable PGx | CPIC recommends dose reduction in PMs; FDA states use with caution |
| Ibuprofen | CYP2C9 | PK Only | Moderate PM | A | 1A | CPIC recommends dose reduction in PMs; FDA states *3 allele carriers or PMs may have higher systemic concentrations | |
| Imipramine | CYP2C19 | Not included | Optional UM/RM/PM | B | 1A | NA | CPIC provides optional recommendation to avoid tertiary amines in UM/RM/PMs |
| CYP2D6 | PK Only | Optional | B | 1A | Actionable PGx | CPIC lists additional gene (CYP2C19), provides dose guidance, and states alternative therapy in UMs and PMs; FDA states alters systemic concentrations | |
| Meloxicam | CYP2C9 | Recommendation | Moderate IM (AS of 1) and PM | A | 1A | Actionable PGx | CPIC recommends dose reduction in IMs with AS of 1 and recommends alternative therapy in PMs; FDA states PMs or *3 allele carriers have higher systemic concentrations and advises considering dose reductions in PMs |
| Mercaptopurine | TPMT | Recommendation | Strong PM/IM | A | 1A | Testing recommended | CPIC recommends dose guidance in PMs and IMs; FDA provides dose guidance in PMs and states IMs may require dosage reduction based on tolerability |
| NUDT15 | Recommendation | Strong PM/IM | A | 2B | Testing recommended | ||
| Nortriptyline | CYP2D6 | PK Only | Strong UM/PM, moderate IM | A | 1A | Actionable PGx | CPIC provides dose guidance; FDA states alternative therapy in UMs and PMs or dose reduction in PMs |
| Omeprazole | CYP2C19 | PK Only | Moderate for RM, NM, and PM | A | 1A | Actionable PGx | CPIC provides dosing recommendations for all phenotypes; FDA states IM and PMs may have higher systemic concentrations only |
| Oxcarbazepine | HLA-A | Not included | Strong/optional | C | 3 | NA | CPIC recommends avoiding use if oxcarbazepine naïve and alternative agents are available; FDA does not mention HLA-A |
| HLA-B | Potential Impact | Strong/optional | A | 1A | Testing recommended | CPIC recommends avoiding use if oxcarbazepine naïve and alternative agents are available; FDA states higher adverse reaction risk only | |
| Pantoprazole | CYP2C19 | Recommendation | Moderate for RM, NM, and PM | A | 1A | Actionable PGx | CPIC provides dosing recommendations for all phenotypes; FDA states PMs may have higher systemic concentrations and advises considering dose reduction in children |
| Paroxetine | CYP2D6 | PK Only | Strong UM, optional PM | A | 1A | Informative PGx | CPIC recommends alternative for UMs and dose reduction for PMs; FDA states alters systemic concentrations only |
| Piroxicam | CYP2C9 | Recommendation | Moderate PM/IM | A | 1A | Actionable PGx | CPIC recommends avoiding use in IMs with AS of 1 and PMs; FDA states consider reducing dosage in PMs |
| Simvastatin | SLCO1B1 | Potential Impact | Strong | A | 1A | NA | CPIC provides dose guidance and states consider alternative statins as an option; FDA states risk of adverse reaction is higher at high doses only |
| Succinylcholine | BCHE | Recommendation | C/D | 3 | Actionable PGx | CPIC guidelines mention 2 genes (CACNA15 and RYR1); FDA recommendations are based on a different gene: BCHE | |
| CACNA15 | Not included | Strong (selected genes) | A | 1A | Actionable PGx | ||
| RYR1 | Not included | Strong | A | 1A | Actionable PGx | ||
| Tacrolimus | CYP3A5 | Recommendation | Strong NM/IM | A | 1A | NA | CPIC provides dose guidance; FDA states may result in lower systemic concentrations and adjust dose based on trough concentrations |
| Tamoxifen | CYP2D6 | PK Only | Strong or moderate depending on AS | A | 1A | Actionable PGx | CPIC provides dose and drug selection guidance; FDA states impact on efficacy not well established |
| Thioguanine | TPMT | Recommendation | Strong PM, moderate IM | A | 3 | Testing recommended | CPIC recommends dose guidance in PMs and IMs; FDA provides dose guidance in PMs and states IMs may require dosage reduction based on tolerability |
| NUDT15 | Recommendation | Strong PM, moderate IM | A | 3 | Testing recommended | ||
| Tramadol | CYP2D6 | Recommendation | Strong UM/PM | A | 1B | Actionable PGx | CPIC recommends avoiding use in UMs and PMs; FDA states risks in UMs and avoid use in children under 12 |
| Trimipramine | CYP2D6 | PK Only | Optional | B | 1A | Actionable PGx | CPIC lists additional gene (CYP2C19) and lists dose guidance or alternative therapy in UMs and PMs |
| CYP2C19 | Not included | Optional UM/RM/PM | B | 1A | NA | CPIC provides optional recommendation to avoid tertiary amines in UMs/RMs/PMs. Gene-drug pair not included in FDA table. | |
| Voriconazole | CYP2C19 | PK Only | Moderate UM/RM/PM | A | 1A | Actionable PGx | CPIC recommends alternative for UMs, RMs, and PMs; FDA states higher concentrations in IM and PMs |
| Warfarin | CYP2C9 | Recommendation | Strong or moderate | A | 1A | Actionable PGx | CPIC provides specific dose guidance and algorithm; FDA states may alter systemic concentrations and dosage requirements |
| CYP4F2 | Recommendation | Optional | A | 1A | NA | ||
| VKORC1 | Recommendation | Strong or moderate | A | 1A | Actionable PGx |
Abbreviations: AS, activity score; CPIC; Clinical Pharmacogenetics Implementation Consortium; FDA; Food and Drug Administration; IM, intermediate metabolizer; NA, not applicable; NM, normal metabolizer; PGx, pharmacogenetics; PM, poor metabolizer; RM, rapid metabolizer; UM, ultrarapid metabolizer.
aOchre color denotes drugs listed in both CPIC guidelines and the FDA Table for which dosing or use recommendations provided in the 2 sources differ; red denotes drugs for which additional or different gene-drug associations are mentioned.
b“Recommendations” denotes therapeutic management recommendations; “Potential Impact,” potential impact on safety or response; “PK Only,” impact on pharmacokinetics only.