Voriconazole
Voriconazole is an antifungal used to treat invasive aspergillosis, and serious infections caused by Scedosporium spp., Fusarium spp., or invasive fluconazole-resistant Candida.
- To guide dose adjustment in order to optimise efficacy and reduce the risk of toxicity.
- Significant intra- and inter-individual pharmacokinetic variability in all patient populations.
- Metabolised by CYP2C19 and strong inhibitor of CYP3A.
- Subject to CYP2C19 genetic polymorphisms and CYP3A drug-drug interactions.
- Non-linear saturable metabolism
- Small changes in dose may produce disproportional changes in plasma concentration.
- Metabolised by CYP2C19 and strong inhibitor of CYP3A.
Assay details
See Voriconazole, Serum – Canterbury Health Laboratories (chl.co.nz)
Timing of concentration sample collection
- With respect to dose interval:
- Take a trough concentration (just before the next dose is due) once at steady-state.
- With respect to treatment course:
- Steady-state concentrations are achieved within 24 hours if oral or IV loading doses are given.
- Without the loading dose, steady-state concentrations are generally achieved within 6 days.
Reference Range
1-5 mg/L
- A trough concentration of ≥ 1-2 mg/L has been associated with improved clinical outcomes in the treatment of invasive fungal infections.
- A trough concentration of ≥ 6 mg/L is most predictive of voriconazole-associated hepatotoxicity and neurotoxicity (visual disturbances, hallucinations and encephalopathy).
- Although no clear exposure–response relationship has been established for voriconazole prophylaxis, breakthrough fungal infections are reported to be more likely with a trough concentration of ≤ 1.5–2 mg/L.
Factors affecting interpretation
Factors that may give a false assay result
Nil known
Dose individualisation and adjustment
- Non-linear saturable metabolism: small changes in dose may produce disproportional changes in plasma concentration.
- Round dose to nearest 50 mg increment (smallest tablet strength is 50 mg).
- Dose adjustment may result in dosing outside of that which is Medsafe-approved.
Contacts for help with interpretation
Medicines Information phone: 03 364 0900 | email: medicines.information@cdhb.health.nz
- Data Sheet: VFEND® (voriconazole) [Internet]. Auckland (NZ): Pfizer New Zealand Pty Ltd; [cited 2024 Jul 3]. Available from: http://www.medsafe.govt.nzhttps://www.medsafe.govt.nz/profs/datasheet/v/Vfendtabinj.pdf/profs/datasheet/v/vttacktab.pdf
- Shen K, Gu Y, Wang Y, Lu Y, Ni Y, Zhong H, et al. Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases. Ther Adv Drug Saf. 2022 Jan 1;13:20420986221127504.
- Abdul-Aziz MH, Alffenaar JWC, Bassetti M, Bracht H, Dimopoulos G, Marriott D, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper. Intensive Care Med. 2020 Jun;46(6):1127–53.
- Luong ML, Al-Dabbagh M, Groll AH, Racil Z, Nannya Y, Mitsani D, et al. Utility of voriconazole therapeutic drug monitoring: a meta-analysis. J Antimicrob Chemother. 2016 Jul;71(7):1786–99.
- Park WB, Kim NH, Kim KH, Lee SH, Nam WS, Yoon SH, et al. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clin Infect Dis Off Publ Infect Dis Soc Am. 2012 Oct;55(8):1080–7.
- Johnson MD, Lewis RE, Dodds Ashley ES, Ostrosky-Zeichner L, Zaoutis T, Thompson GR, et al. Core Recommendations for Antifungal Stewardship: A Statement of the Mycoses Study Group Education and Research Consortium. J Infect Dis. 2020 Aug 5;222(Suppl 3):S175–98.
- John J, Loo A, Mazur S, Walsh TJ. Therapeutic drug monitoring of systemic antifungal agents: a pragmatic approach for adult and pediatric patients. Expert Opin Drug Metab Toxicol. 2019 Nov;15(11):881–95.
Last updated
November 2024