Ganciclovir therapeutic drug monitoring in transplant recipients

Background: The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance. Objectives: To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population. Methods: An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (C-min) of 1-2 mg/L and an AUC(24h) of >50 mg.h/L were aimed for. For treatment, a C-min of 2-4 mg/L and an AUC(24h) of 80-120 mg.h/L were aimed for. Results: Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR 2-6) per patient. The median C-min and AUC(24h) in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg.h/L and 0.9 mg/L and 67 mg.h/L, respectively. Significant introand inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m(2) and patients on continuous veno-venous haemofiltration showed underexposure. The highest C-min and AUC(24h) values were associated with the increase in Liver function markers and decline in WBC count as compared with baseline. Conclusions: This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir C-min and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study.