LAUSR

Learning Objectives: The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. Methods: We conducted a single center, retrospective analysis of adult patients with active viral infection treated with valganciclovir or intravenous ganciclovir with clinician-directed TDM between January 2005 and November 2015. The primary outcome was an association between serum ganciclovir TDM and clinical efficacy endpoints within 30 days of treatment, including virologic reduction and clinical success, as defined by viral load and symptomatology. Secondary outcomes included the safety endpoints of leukopenia, neutropenia, thrombocytopenia, anemia, nephrotoxicity, and neurotoxicity, evaluated at any time and within seven days after the last administered dose of ganciclovir or valganciclovir. Results: Of 175 patients who had ganciclovir TDM, 97 were included in our analysis. Nearly all patients were treated for cytomegalovirus (CMV) infection (94.8%) with a median (IQR) baseline CMV viral load of 5,500 (2,500–11,500) copies/ml. The majority achieved virologic reduction with an undetectable or less than lower limit of quantification level (72.2%) and virologic reduction and improvement in symptomatology (70.1%) at 30 days. Among patients with detectable CMV viremia at 30 days, viral load had declined to a median of 1,500 (1,000–3,875) copies/ml. We did not observe significant associations between the efficacy outcomes and serum ganciclovir trough (p=0.19 and p=0.1, respectively) or peak concentrations (p=0.25 and p=0.29, respectively). Similarly, there was no significant association between serum ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (p=0.4, p=0.5), neutropenia (p=0.56, p=0.69), thrombocytopenia (p=0.21, p=0.56), anemia (p=0.73, p=0.24), nephrotoxicity (p=0.44, p=0.7), and neurotoxicity (p=0.43, p=0.48). Conclusions: This study did not observe any associations between serum ganciclovir concentrations and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamic profiles in whom ganciclovir TDM may be of benefit.