TABLE 2.
Proposed drug-gene pairs for the clinical implementation of pharmacogenomics (PGx).
| Indications | Drugs | Genes | PHARMGKB b https://www.pharmgkb.org/ | CPIC c https://cpicPGx.org/ | FDA d https://www.fda.gov/ | EMA e https://www.ema.europa.eu/en | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Classes | Name | On WHO list of essential medicines a | Level of evidence of PGx clinical annotation | Recommendation | Drug label annotation Tag | PGx level | Drug label annotation Tag | PGx level | Drug label annotation Tag | ||
| Autoimmune Diseases | Antigout | Allopurinol | Yes | HLA-B | 1A | Yes | Pediatric | Testing Recommended | Alternate drug, Prescribing info | - | - |
| Cardiovascular Diseases | Anticoagulant | Warfarin | Yes | CYP2C9, VKORC1 | 1A | Yes | Pediatric | Actionable PGx | Prescribing Info | - | - |
| CYP4F2 | 1A | Yes | Pediatric | - | - | - | - | ||||
| Antiplatelet | Clopidogrel | Yes | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | Prescribing Info | Actionable PGx | - | |
| Statins | Atorvastatin | Yes | SLCO1B1 | 1A | Yes | Dosing info, Pediatric | Informative PGx | - | - | - | |
| Rosuvastatin | - | ABCG2, SLCO1B1 | 1A | Yes | Alternate drug, Dosing info, Pediatric | Actionable PGx | - | - | - | ||
| Simvastatin | Yes | SLCO1B1 | 1A | Yes | Alternate drug, Dosing info, Pediatric | Informative PGx | - | - | - | ||
| Gastrointestinal diseases | Antiemetic | Ondansetron | Yes | CYP2D6 | 1A | Yes | Pediatric | Informative PGx | - | - | - |
| Proton pump inhibitors | Dexlansoprazole | - | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | |
| Lansoprazole | - | CYP2C19 | 1A | Yes | Pediatric | Informative PGx | - | - | - | ||
| Omeprazole | Yes | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Pantoprazole | - | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | Prescribing info, Pediatric | - | - | ||
| Infectious diseases | Antibiotics | Gentamicin | Yes | MT-RNR1 | 1A | Yes | Alternate drug, Pediatric | - | - | - | - |
| Streptomycin | - | MT-RNR1 | 1A | Yes | Alternate drug, Pediatric | - | - | - | - | ||
| Tobramycin | Yes | MT-RNR1 | 1A | Yes | Alternate drug, Pediatric | - | - | - | - | ||
| Antifungal | Voriconazole | Yes | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | - | Informative PGx | - | |
| Antivirals | Abacavir | Yes | HLA-B | 1A | Yes | Pediatric | Testing Required | Alternate drug, Prescribing info | Testing Required | Alternate drug, Prescribing info | |
| Atazanavir | Yes | UGT1A1 | 1A | Yes | Pediatric | - | - | - | - | ||
| Efavirenz | Yes | CYP2B6 | 1A | Yes | Pediatric | Actionable PGx | - | Actionable PGx | - | ||
| Neuropsychiatric diseases | Antiepileptics | Carbamazepine | Yes | HLA-A | 1A | Yes | Alternate drug, Pediatric | Actionable PGx | - | - | - |
| HLA-B | 1A | Yes | Alternate drug, Pediatric | Testing Required | Alternate drug, Prescribing info | - | - | ||||
| Oxcarbazepine | - | HLA-B | 1A | Yes | Alternate drug | Testing Recommended | Alternate drug, Prescribing info | - | - | ||
| Phenytoin | Yes | CYP2C9, HLA-B | 1A | Yes | Pediatric | Actionable PGx | Prescribing info | - | - | ||
| Non-opioid analgesic | Celecoxib | - | CYP2C9 | 1A | Yes | Pediatric | Actionable PGx | Dosing info, Prescribing info | - | - | |
| Opioid analgesics | Codeine | Yes | CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | Alternate drug, Prescribing info, Pediatric | - | - | |
| Tramadol | - | CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | Alternate drug, Prescribing info | - | - | ||
| Antidepressants | Amitriptyline | Yes | CYP2C19 | 1A | Yes | Pediatric | - | - | - | - | |
| CYP2D6 | - | Yes | Pediatric | Actionable PGx | - | - | - | ||||
| Aripiprazole | - | CYP2D6 | 1A | - | - | Actionable PGx | Dosing info, Prescribing info | Actionable PGx | Dosing info, Prescribing info | ||
| Citalopram | Yes | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | Dosing info, Prescribing info | - | - | ||
| Clomipramine | Yes | CYP2C19 | 1A | Yes | Pediatric | - | - | - | - | ||
| CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||||
| Desipramine | - | CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Doxepin | - | CYP2C19, CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Escitalopram | Yes | CYP2C19 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Fluvoxamine | Yes | CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Imipramine | - | CYP2C19 | 1A | Yes | Pediatric | - | - | - | - | ||
| CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||||
| Nortriptyline | - | CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||
| Paroxetine | Yes | CYP2D6 | 1A | Yes | Pediatric | Informative PGx | - | - | - | ||
| Sertraline | Yes | CYP2C19 | 1A | Yes | Pediatric | - | - | - | - | ||
| Trimipramine | - | CYP2C19 | 1A | Yes | Pediatric | - | - | - | - | ||
| CYP2D6 | 1A | Yes | Pediatric | Actionable PGx | - | - | - | ||||
| Venlafaxine | - | CYP2D6 | 1A | - | - | Actionable PGx | - | - | - | ||
| Oncology | Cytotoxic therapy | Capecitabine | Yes | DPYD | 1A | Yes | Pediatric | Actionable PGx | Prescribing Info | Testing Recommended | Alternate drug, Prescribing info |
| Fluorouracil | Yes | DPYD | 1A | Yes | Pediatric | Actionable PGx | Alternate drug, Prescribing info | - | - | ||
| Mercaptopurine | Yes | NUDT15, TPMT | 1A | Yes | Pediatric | Testing Recommended | Dosing info, Prescribing info | Actionable PGx | Prescribing Info | ||
| Thioguanine | - | NUDT15, TPMT | 3 | Yes | Pediatric | Testing Recommended | Dosing info, Prescribing info | - | - | ||
| Hormonal therapy | Tamoxifen | Yes | CYP2D6 | 1A | Yes | - | Actionable PGx | - | - | - | |
| Immunosuppressants | Azathioprine | Yes | NUDT15, TPMT | 1A | Yes | Pediatric | Testing Recommended | Prescribing info | - | - | |
| Tacrolimus | Yes | CYP3A5 | 1A | Yes | Pediatric | Informative PGx | - | - | - | ||
PharmGKB, clinical annotations levels range from 1-4, with level 1 meeting the highest criteria.
CPIC, provides guidelines that help in implementing pharmacogenomics tests into clinical practice setting.
FDA, approves and monitors drugs and other biological products for ensuring safety and effectiveness in the United States of America.
EMA, approves and monitors drugs and other biological products for ensuring safety and effectiveness within the European union and economic area.
Testing Required: Genetic testing is obligatory before prescribing the drug.
Testing Recommended: Genetic testing should be considered before prescribing the drug.
Actionable PGx: Genetic testing is available and advised due to possible gene-drug relation, but it is not required.
Informative PGx: Genetic testing is not required. Gene variants do not affect drug response, or the effect is not clinically significant.
Dosing info: Tag implies that dose adjustment is required.
Alternate drug: Tag implies that a drug substitute is recommended.
Prescribing info: Tag implies that dose adjustment or drug substitution is either required or suggested, drug should be used with caution, or patients should be monitored for adverse reactions.
Pediatric: Tag implies that a drug contains PGx information for pediatric population.