Jarrett R. Amsden

Introduction: Triazole antifungal agents are prescribed to treat invasive fungal infections in neutropenic and non-neutropenic patients. These antifungal agents are substrates and inhibitors of cytochrome P450 (CYP). Genetic polymorphisms in CYP2C9, CYP2C19 and CYP3A5 can lead to large population-specific variations in drug efficacy and safety, optimal dosing, or contribute to drug interactions associated with this class. Areas covered: This manuscript reviews the pharmacogenomics (i.e. the influence of genetics on drug disposition) of triazole antifungal agents related to their CYP-mediated metabolism and summarizes their implications on triazole efficacy, safety, and tolerability. A search of English language original research, and scholarly reviews describing the pharmacogenomics of triazole antifungal agents and their impact on drug efficacy, safety, and tolerability published from 1980 to present was undertaken using PubMed. Expert opinion: Currently studies demonstrating the pharmacogenomic influences on itraconazole, posaconazole and isavuconazole are minimal and limited to their inhibitory effects on CYP3A4 in expressors of CYP3A5 variants. Conversely, there are significant pharmacogenomic considerations for voriconazole because it interacts with several polymorphic CYPs, most notably CYP2C19. Pharmacogenomics of CYP2C9 do not appear to effect fluconazole safety and efficacy. However, genetic polymorphisms may influence its drug interactions but this needs further study.

Voriconazole (VCZ) is frequently utilized for prevention and treatment of invasive fungal infections in peripheral stem cell transplant (PSCT) patients. We performed an open-label pharmacokinetic study to compare VCZ and N-oxide voriconazole (N-oxide VCZ) pharmacokinetics in patients pre- and post-PSCT. Ten patients completed both sampling periods. The pharmacokinetics of VCZ were unchanged; however, those of N-oxide VCZ were significantly different pre- and post-PSCT.

West Nile virus can cause a febrile illness that may progress to meningoencephalitis. The only available treatments are ribavirin (although it has had limited success in humans) and interferon α‐2b. A small pilot study showed that starting treatment with interferon α‐2b on days 1–4 of hospital admission may reduce disease severity and complications. We encountered an 83‐year‐old man with West Nile meningoencephalitis who began taking interferon α‐2b 3 weeks after disease presentation. Although studies and reports indicate that treatment is less likely to provide a favorable response if administered after days 1–6 of the disease course, the patient experienced substantial beneficial effects from this treatment. This is the first case report, to our knowledge, that describes successful treatment with interferon α‐2b after several weeks of West Nile virus infection. Further studies are warranted to more fully understand the value of interferon α‐2b in treating West Nile meningoencephalitis.