Monitoring antiviral blood concentrations

Data correlating antiviral plasma concentrations with clinical outcomes are limited; most data available are for aciclovir and ganciclovir. Consequently, monitoring antiviral concentrations is uncommon.

Some patients (eg critically ill patients, transplant recipients, patients on continuous renal replacement therapy) are at risk of low antiviral plasma concentrations leading to treatment or prophylaxis failure, or are at risk of high antiviral concentrations leading to drug toxicity (eg bone marrow suppression with ganciclovir and valganciclovir, neurotoxicity with aciclovir and valaciclovir).

If monitoring is required for patients taking aciclovir or valaciclovir (a prodrug of aciclovir), monitor aciclovir plasma concentration. The suggested target trough plasma concentration for encephalitis is between 2 and 4 mg/LAbdul-Aziz 2020Lim 2009Pouplin 2011.

If monitoring is required for patients taking ganciclovir or valganciclovir (an oral prodrug of ganciclovir), monitor ganciclovir plasma concentration. The area under the concentration–time curve over a 24-hour period (AUC24) can be difficult to determine for ganciclovir if model-informed precision dosing software is unavailable. The correlation between target trough concentrations and target AUC24 depends on the dosing frequency and the formulation being used (eg oral valganciclovir, intravenous ganciclovir). These factors should be considered when interpreting ganciclovir plasma concentrations – seek expert advice. The target plasma concentration required depends on the type of therapy; see Target ganciclovir plasma concentrations based on type of therapy.
Table 1. Target ganciclovir plasma concentrations based on type of therapy

[NB1]Abdul-Aziz 2020Asberg 2014Krens 2020Martson 2021Padulles 2016Selby 2021Stockmann 2015

Type of therapy

Target AUC24

Target trough concentration

Prophylaxis

40 to 60 mg.hr/L

1 to 2 mg/L

Induction phase of treatment

80 to 120 mg.hr/L

1.5 to 4 mg/L

Maintenance phase of treatment

40 to 60 mg.hr/L

1 to 2 mg/L

Note:

AUC24 = area under the concentration–time curve over a 24-hour period

NB1: The correlation between target trough concentrations and target AUC24 depends on the dosing frequency and the formulation being used (eg oral valganciclovir, intravenous ganciclovir). These factors should be considered when interpreting ganciclovir plasma concentrations – seek expert advice.

There are data that a ganciclovir AUC24 more than 60 mg.hr/L is associated with neutropeniaWiltshire 2005. There is a weak correlation between a ganciclovir AUC24 more than 50 mg.hr/L and anaemiaPadulles 2016.

For information on monitoring antiviral concentrations, see the International Association for Therapeutic Drug Monitoring and Clinical Toxicology position paper.