Table 5.
Comparison of HLA genotyping and clinical recommendations provided by different international pharmacogenetics working bodies and drug regulatory agency.
| Drug | Gene | Phenotype | Clinical Recommendations |
Recom. Authority |
Level of Evidence | Genotyping Recommendations |
|---|---|---|---|---|---|---|
| Carbamazepine | HLA | HLA-B*15:02 negative and HLA-A*31:01 negative | Use standard dose as per guidelines | CPIC | 1A | Strong |
| HLA-B*15:02 negative and HLA-A*31:01 positive | If patient is CBZ-naïve and alternative agents are available, do not use CBZ | CPIC | 1A | Strong | ||
| HLA-B*15:02 positive and any HLA-A*31:01 genotype | If patient is CBZ-naïve, do not use CBZ | CPIC | 1A | Strong | ||
|
HLA-B*15:02, HLA-A*31:01 and HLA-B*15:11 carriers |
Choose an alternative | DPWG | 4E | Essential | ||
| HLA-B*15:02 positive | Alternative medication should be used as first-line therapy. | CPNDS | +++ | B-Moderate | ||
| HLA-A*31:01 positive | Alternative medication should be used as first-line therapy | CPNDS | +++ | B-Moderate | ||
| HLA-B*15:02 positive | CBZ is not recommended unless the benefits clearly outweigh the risks | FDA | - | - | ||
| HLA-A*31:01 positive | Risks and benefits should be weighed before prescription of CBZ | FDA | - | - | ||
| Oxcarbazepine | HLA -B | HLA-B*15:02 negative | Use OXC per standard dosing guidelines | CPIC | 1A | Strong |
| HLA-B*15:02 positive | If patient is oxcarbazepine naïve, do not use oxcarbazepine. | CPIC | 1A | Strong | ||
| HLA-B*15:02 positive | An alternative is recommended. If not possible, it is recommended to advise the patient to report any rash immediately. | DPWG | 4D | Beneficial (patients of Asian, not-Japanese and not-Korean, descent) | ||
| HLA-B*15:02 positive | Patients are at higher risk of SCARs. Genotyping is not a substitute for clinical vigilance | FDA | - | - | ||
| Abacavir | HLA -B | HLA-B*57:01 negative | Use abacavir per standard dosing guidelines | CPIC | 1A | Strong |
| HLA-B*57:01 positive | Abacavir is not recommended | CPIC | 1A | Strong | ||
| HLA-B*57:01 positive | Abacavir is contra-indicated. | DPWG | 4E | Essential | ||
| HLA-B*57:01 positive | Do not use abacavir | FDA | - | - | ||
| Allopurinol | HLA -B | HLA-B*58:01 negative | Use allopurinol per standard dosing guidelines | CPIC | 1A | Strong |
| HLA-B*58:01 positive | Allopurinol is contraindicated. | CPIC | 1A | Strong | ||
| HLA-B*58:01 positive | Choose an alternative, e.g., febuxostat or to precede treatment with allopurinol tolerance induction. | DPWG | 4F | - | ||
| HLA-B*58:01 positive | Results in higher severe skin reactions | FDA | - | - | ||
| Phenytoin | HLA -B | HLA-B*15:02 negative | Initiate therapy with recommended maintenance dose | CPIC | 1A | Strong |
| HLA-B*15:02 positive | If patient is phenytoin naive, do not use phenytoin | CPIC | 1A | Strong | ||
| HLA-B*15:02 positive | Phenytoin can induce the life-threatening cutaneous adverse events | DPWG | 4E | Beneficial (patients of Asian, but not Japanese and Korean descent) | ||
| Lamotrigine | HLA -B | HLA -B *15 :02 | Considers genotyping of patients to be beneficial for drug safety. Avoided lamotrigine if possible, even if both the incidence and the risk increase are low | DPWG | 4E | Beneficial (patients of Asian but not Japanese and Korean descent) |
| Flucloxacillin | HLA -B | HLA -B *57 :01 | Regularly monitor the patient’s liver function. Choose an alternative if liver enzymes and/or bilirubin levels are elevated | DPWG | 4F | - |
| Lamotrigine | HLA -B | HLA -B *15 :02 | Considers genotyping of patients to be beneficial for drug safety. Avoided lamotrigine if possible, even if both the incidence and the risk increase are low | DPWG | 4E | Beneficial (patients of Asian but not Japanese and Korean descent) |
| Flucloxacillin | HLA -B | HLA -B *57 :01 | Regularly monitor the patient’s liver function. Choose an alternative if liver enzymes and/or bilirubin levels are elevated | DPWG | 4F | - |
HLA = Human leukocyte antigen; Recom = Recommending; CBZ = Carbamazepine; CPIC = Clinical Pharmacogenetics Implementation Consortium; DPWG = Dutch Pharmacogenetics Working Group; CPNDS = Canadian Pharmacogenomics Network for Drug Safety.