Monitoring voriconazole blood concentrations

Monitor voriconazole plasma concentration if voriconazole prophylaxis or treatment is likely to be used for longer than a few days.

The metabolism of voriconazole is saturable, leading to nonlinear pharmacokinetics, and exposure varies considerably between patients. Voriconazole plasma concentration monitoring has been demonstrated in a randomised controlled trial and observational studies to improve outcomesLuong 2016Park 2012.

Voriconazole plasma concentrations should be measured at least 2 to 5 days after starting therapy or changing the doseChau 2021Park 2012. A trough concentration between 1 and 5.5 mg/L is associated with clinical efficacy; however, voriconazole trough concentrations above 4.5 mg/L should be avoidedChau 2021. Central nervous system infections, bulky disease or multifocal infections required trough concentrations more than 2 mg/LChau 2021. Significant neurotoxicity has been observed when a high voriconazole trough concentration (more than 4.5 or 6 mg/L) is sustainedAbdul-Aziz 2020Dolton 2012Pascual 2008Suzuki 2013. There is a possible correlation between high voriconazole trough concentrations and hepatotoxicity; however, data supporting this correlation are inconsistentDolton 2012Suzuki 2013.

If voriconazole plasma concentrations remain subtherapeutic after 2 appropriate dose adjustments, switch to an antifungal with metabolism independent of CYP2C19. Perform CYP2C19 genotype testing in these patients; some patients are CYP2C19 ultrarapid or rapid metabolisersChau 2021.

For information about voriconazole plasma concentration monitoring in haematology patients, see the Australian and New Zealand antifungal consensus guidelines.