Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult solid organ transplant recipients

Abstract

Summary Human cytomegalovirus (CMV) represents the most common infection among recipients of solid organ transplants (SOTs). Previous meta‐analysis showed 0.8% of SOT recipients developed CMV disease whilst receiving valganciclovir (ValGCV) prophylaxis. However, the clinical utility of monitoring ganciclovir (GCV) blood concentrations is unclear. We systematically reviewed the association between GCV concentrations during prophylaxis and the incidence of CMV. MEDLINE and EMBASE databases were searched for studies between 1946 and 2018, where GCV pharmacokinetics and incidence of CMV viraemia or disease in SOT were available. Research designs included randomised trials, comparative, prospective cohort, retrospective, or case report studies. Only human adult studies were included, with English language restriction. The 11 studies that met the eligibility criteria included 610 participants receiving GCV or ValGCV prophylaxis. Quality assessment showed 2/4 randomised trials, 4/6 cohort studies, and 1/1 case report were of high quality. Despite dose adjustments for renal impairment, mean GCV exposures for patients were heterogeneous and ranged between 28 and 53.7 μg·h/mL across three randomised trials. The incidence of CMV infection and disease ranged from 0% to 50% and 0% to 3.1%, respectively, with follow up between 3 to 9 months. One study showed statistical power in determining relationship, where GCV exposure at 40 to 50 μg·h/mL in high‐risk SOT recipients was associated with a reduced risk of viraemia. Clinical monitoring for GCV exposure can be applied to high‐risk SOT recipients during ValGCV prophylaxis; however, further studies are needed to determine the utility of monitoring in all SOT recipients.

Paediatric ganciclovir dosing in extracorporeal membrane oxygenation: Is standard dosing good enough?

“…The recommended dose of ganciclovir in children at 5 mg/kg every 12 hours has been extrapolated primarily from adult studies, with only small cohort studies completed in children. 2 These studies evaluated paediatric patients with very select disease processes and may not represent real-world patient care situations. Additionally, inter-patient variability in children is well-documented with potential underdosing in children compared to adults.…”

Possibilities Of Prevention And Treatment Of Human Cytomegalovirus Infections Including New Drugs And Compounds With Potential Application

“…However, despite the diagnostic and therapeutic solutions in the form of antiviral drugs, the hCMV is still a significant cause of organ infections (most often: pneumonia, liver, retina, and intestinal diseases) as well as systemic disorder. It is also one of the most important viruses associated with the post-transplantation complications, transplant failure, as well as deaths among recipients of allogeneic hematopoietic cells (allo-HCT) and organs [1,5,19,30,35,39].…”

“…This is mainly used among patients who are at a very high risk of developing a disease caused by the CMV infection. The use of chemoprophylaxis allows the reduction of morbidity and mortality as a result of cytomegalovirus infection, especially among patients after hematopoietic cell transplantation [2,5,12,19,20,39].…”

Population Pharmacokinetics and Bayesian Estimation of the Area Under the Concentration‐Time Curve for Ganciclovir in Adult Chinese Renal Allograft Recipients After Valganciclovir Administration

“…The pharmacokinetics (PK) of GCV are highly variable after VGCV administration; therefore, it is difficult to achieve GCV exposure within a therapeutic range after a standard dosing regimen 14 . Therapeutic drug monitoring (TDM) is suggested to be useful in individualized therapy 15–18 . In a previous study conducted in a group of 240 high‐risk transplantation patients, it was suggested that the monitoring of GCV exposure in both adult and pediatric solid‐organ transplantation patients receiving VGCV therapy is helpful.…”

“…14 Therapeutic drug monitoring (TDM) is suggested to be useful in individualized therapy. [15][16][17][18] In a previous study conducted in a group of 240 high-risk transplantation patients, it was suggested that the monitoring of GCV exposure in both adult and pediatric solid-organ transplantation patients receiving VGCV therapy is helpful. The area under the concentration time curve (AUC) in the range of 40-50 μgh/mL in patients after a once-daily dose at steady state predicted a low incidence of breakthrough viremia during prophylaxis.…”