For the TREATMENT of invasive fungal infections:
Ultrarapid Metabolizer
Clinical Implication
- Increased CYP2C19 enzyme activity.
- Increased risk of subtherapeutic concentrations and treatment failure.
Therapeutic Recommendation
- Choose an alternative agent that is not dependent on CYP2C19 metabolism (e.g., isavuconazole, liposomal amphotericin B, and posaconazole).
Rapid Metabolizer
Clinical Implication
- Increased CYP2C19 enzyme activity.
- Increased risk of subtherapeutic concentrations and treatment failure.
Therapeutic Recommendation
- Choose an alternative agent that is not dependent on CYP2C19 metabolism (e.g., isavuconazole, liposomal amphotericin B, and posaconazole).
- For pediatric patients: Alternatively may be acceptable to initiate standard dosing with therapeutic drug monitoring, however it may be difficult to obtain therapeutic levels in a timely manner.
Normal Metabolizer
Clinical Implication
- Normal CYP2C19 enzyme activity.
- Normal response expected.
Therapeutic Recommendation
- Use standard dose of voriconazole.
Intermediate Metabolizer
Clinical Implication
- Decreased CYP2C19 enzyme activity.
- Higher dose-adjusted trough concentrations and potential for increased risk of adverse effects (e.g., hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders).
Therapeutic Recommendation
- Use standard dose of voriconazole.
Poor Metabolizer
Clinical Implication
- No CYP2C19 enzyme activity.
- Increased risk of adverse effects (e.g., hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disorders).
Therapeutic Recommendation
- Choose alternative agent that is not dependent on CYP2C19 metabolism (e.g., isavuconazole, liposomal amphotericin B, and posaconazole).
- If voriconazole is warranted, administer lower doses with therapeutic drug monitoring.
Unable to Genotype or Assay Failure
- The analysis failed to yield an informative result and thus no genotype is reported.
Unknown Phenotype
- This individual is carrying at least one allele with uncertain/unknown function and the predicted phenotype cannot be determined at this time.
Reference
- Moriyama B et al. Clin Pharmacol Ther. 2017 Jul;102(1):45-51. PMID: 27981572.