Table 2. The Clinical Pharmacogenetics Implementation Consortium (CPIC) level A gene/drug pairs.
The CPIC considers all level A drugs to have high or moderate evidence in favor of using available genetic information when prescribing treatment, and at least one moderate or strong clinical action is recommended in the CPIC guidelines. The common genetic variants that influence the response of each drug is included along with a description of the potential benefit of using pharmacogenetics to prescribe medications and the level of evidence to assess the clinical utility of pharmacogenetic testing.
| Drug | Genetic* variants | Potential Pharmacogenetic Benefit* | Level of Evidence to Assess Clinical Utility | Food and Drug Administration Labeling Requirement for Testing* |
|---|---|---|---|---|
| Antithrombic | ||||
| Clopidogrel | CYP2C19*1, *2, *3, *17 | Prevent cardiovascular events in patients with acute coronary syndromes undergoing percutaneous coronary intervention | Six randomized controlled trials† Conflicting evidence for pharmacogenetics. |
Not required |
| Warfarin | CYP2C9*1, *2, *3, *5, *6, *8, *11, rs12777823, VKORC1 –1639G>A, CYP4F2*3 | Achieve therapeutic INR faster, increase time within therapeutic INR, reduce adverse bleeding events | Three large randomized controlled trials‡ Conflicting evidence for pharmacogenetics. |
Not required |
| Narcotics | ||||
| Codeine | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Identify patients with either high risk of drug toxicity (respiratory depression, nausea, vomiting, constipation) or ineffective response to codeine | No studies | Not required |
| Oxycodone (refer to codeine CPIC guideline) |
CYP2D6*1, *2, *3, *4, *5, *6 | Identify patients with either high risk of drug toxicity (respiratory depression, nausea, vomiting, constipation) or ineffective response to oxycodone | No studies | Not required |
| Tramadol (refer to codeine CPIC guideline) |
CYP2D6*1, *2, *3, *4, *5, *6, *10 | Prevent adverse events (respiratory depression, cardiotoxicity, or nausea) and maintain drug efficacy | No studies | Not required |
| Antidepressants | ||||
| Amitriptyline |
CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 CYP2C19*1, *2, *3, *17 |
Prevent side effects (anticholinergic, CNS, gastrointestinal, cardiovascular) and increase likelihood of drug efficacy | No studies | Not required |
| Nortriptyline | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Prevent side effects (anticholinergic, CNS, gastrointestinal, cardiovascular) and increase likelihood of drug efficacy | No studies | Not required |
| Fluvoxamine | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Prevent side effects (CNS, gastrointestinal, sexual) | No studies | Not required |
| Citalopram | CYP2C19*1, *2, *3, *17 | Prevent adverse events (CNS, gastrointestinal, sexual, arrhythmias) and increase likelihood of drug efficacy | No studies | Not required |
| Escitalopram | CYP2C19*1, *2, *3, *17 | Prevent adverse events (CNS, gastrointestinal, sexual, arrhythmias) and increase likelihood of drug efficacy | No studies | Not required |
| Paroxetine | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Prevent side effects (CNS, gastrointestinal, sexual) | No studies | Not required |
| Anticonvulsant | ||||
| Carbamazepine | HLA-B*15:02, HLA-A*31:01 | Reduce incidence of Stevens-Johnson syndrome, toxic epidermal necrolysis, maculopapular exanthema, and other cutaneous adverse reactions; greater benefit in Southeast Asian populations (HLA-B*15:02 Allele Frequencies: East Asian 6.9%, Oceanian 5.4%, South/Central Asian 4.6%) | Prospective screening study of HLA-B*15:02 in Taiwan§ Supportive evidence for pharmacogenetics. |
Testing required for HLA-B*15:02 |
| Phenytoin | HLA-B*15:02, CYP2C9*1, *2, *3 | Reduce risk of Steven Johnson Syndrome and toxic epidermal necrolysis in patients with HLA-B*15:02, avoid adverse events (sedation, ataxia, dizziness, nystagmus, nausea, cognitive impairment) in patients who are CYP2C9 poor metabolizers; high frequency of benefit in Southeast Asian populations (HLA-B*15:02 Allele Frequencies: East Asian 6.9%, Oceanian 5.4%, South/Central Asian 4.6%) | No studies | Not required |
| Oxcarbazepine | HLA-B*15:02 | Reduce risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; high frequency of benefit in Southeast Asian populations (HLA-B*15:02 Allele Frequencies: East Asian 6.9%, Oceanian 5.4%, South/Central Asian 4.6%) | No studies | Not required |
| Antiemetic | ||||
| Ondasetron | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Identify patients who do not respond effectively to Ondasetron | No studies | Not required |
| Tropisetron | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *41 | Identify patients who do not respond effectively to Tropisetron | No studies | Not required |
| Anticancer/Immunosuppressive | ||||
| Capecitabine | DYPYD*2A, *13, rs67376798, rs75017182 | Reduce risk of drug toxicity (neutropenia, nausea, vomiting, severe diarrhea, stomatitis, mucositis, hand-foot syndrome) | No studies | Not required |
| Fluorouracil | DYPYD*2A, *13, rs67376798, rs75017182 | Reduce risk of drug toxicity (neutropenia, nausea, vomiting, severe diarrhea, stomatitis, mucositis, hand-foot syndrome) | No studies | Not required |
| Thioguanine | TPMT*1, *2, *3A, *3B, *3C, *4 | Reduce risk of acute myelosuppression and maintain drug efficacy | No studies | Not required |
| Azathioprine | TPMT*1, *2, *3A, *3B, *3C, *4 | Reduce risk of acute myelosuppression and maintain drug efficacy | Two randomized controlled trials|| Supportive evidence for pharmacogenetics. |
Not required |
| Mercaptopurine | TPMT*1, *2, *3A, *3B, *3C, *4 | Reduce risk of acute myelosuppression and maintain drug efficacy | One randomized controlled trial|| Supportive evidence for pharmacogenetics. | Not required |
| Tacrolimus | CYP3A5*1, *3, *6, *7 | Achieve target concentrations faster to reduce risk of graft rejection after transplantation and reduce the risk of drug toxicity (nephrotoxicity, hypertension, neurotoxicity, hyperglycemia) | Two randomized controlled trials¶ Conflicting evidence for pharmacogenetics |
Not required |
| Tamoxifen | CYP2D6*1, *2, *3, *4, *5, *6, *9, *10, *17, *41 | Optimize dose or identify patients who do not respond effectively to Tamoxifen | No studies | Not required |
| Irinontecan (CPIC guideline not yet available) | UGT1A1*1, *28 | Reduce risk for neutropenia, diarrhea, and asthenia | No studies | Not required |
| Anesthetic | ||||
| Isoflurane (CPIC guideline not yet available) | CACNA1S and RYR1 | Reduce risk of malignant hyperthermia | No studies | Not required |
| Desflurane (CPIC guideline not yet available) | CACNA1S and RYR1 | Reduce risk of malignant hyperthermia | No studies | Not required |
| Sevoflurane (CPIC guideline not yet available) | CACNA1S and RYR1 | Reduce risk of malignant hyperthermia | No studies | Not required |
| Antiviral | ||||
| Abacavir | HLA-B*57:01 | Reduce risk of hypersensitivity reactions | Randomized controlled trial with prospective screening for HLA-B*57:01|| Supportive evidence for pharmacogenetics. | Testing required |
| Atazanavir | UGT1A1*28, *37, rs887829 | Identify patients with a high risk of developing hyperbilirubinemia | No studies | Not required |
| Peginterferon alfa-2a | IFNL3 rs12979860 and rs8099917 | Predict drug response and predict eligibility for shorter durations of therapy when used in combination with protease inhibitors | No studies | Not required |
| Peginterferon alfa-2b | IFNL3 rs12979860 and rs8099917 | Predict drug response and eligibility for shorter durations of therapy used in combination with protease inhibitors | No studies | Not required |
| Ribavirin | IFNL3 rs12979860 and rs8099917 | Predict drug response and eligibility for shorter durations of therapy when used in combination with protease inhibitors | No studies | Not required |
| Antifungal | ||||
| Voriconazole | CYP2C19*1, *2, *3, *17 | Prevent side effects (hepatotoxicity, visual disturbances, visual hallucinations) or identify patients who do not respond effectively to Voriconazole | No studies | Not required |
| Antigout | ||||
| Allopurinol | HLA-B*58:01 | Reduce risk of hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis; high frequency of benefit in Han-Chinese and Thai populations (HLA-B*58:01 Allele Frequency: Taiwan Han Chinese 11%) | Prospective screening trial for HLA-B*58:01 in Taiwan§ Supportive evidence for pharmacogenetics. |
Not required |
| Rasburicase | G6PD I, II, III, IV | Reduce risk of acute hemolytic anemia; high frequency of benefit in Asia, Europe, Africa, and the Middle East | No studies | Testing required |
| Cystic Fibrosis | ||||
| Ivacaftor | G551D-CFTR (rs75527207) | Identify patients who could benefit from Ivacaftor treatment | Clinical trials provide supportive evidence for pharmacogenetics.§ | Testing required |
| Paralytic | ||||
| Succinylcholine (CPIC guideline not yet available) |
CACNA1S rs1800559 and rs772226819 | Reduce risk of malignant hyperthermia | No studies | Not required |
| Lipid-lowering | ||||
| Simvastatin | SLCO1B1*1, *5, *15, *17 | Reduce risk of myopathies and rhabdomyolysis | No studies | Not required |