Ganciclovir

Abstract

Ganciclovir is a nucleoside guanosine analogue which incorporates ganciclovir triphosphate (the active moiety) into DNA during elongation, thereby inhibiting viral replication. Comparative studies of pre-emptive and prophylactic ganciclovir therapies in bone marrow transplant (BMT) recipients have shown similar rates of cytomegalovirus (CMV) infection, disease and patient mortality. Long term prophylaxis with either oral, or sequential intravenous/oral, ganciclovir has shown efficacy in renal allograft recipients, including high risk patients or those receiving antilymphocyte antibody therapy. A preliminary study indicates that ganciclovir is more efficacious than aciclovir in paediatric patients. Both oral and intravenous prophylactic ganciclovir regimens have shown efficacy compared with no antiviral treatment in lung transplant recipients; initial reports have shown similar efficacy between pre-emptive and prophylactic ganciclovir. Oral ganciclovir monotherapy is as efficacious as sequential intravenous/oral ganciclovir therapy in liver transplant recipients. Pre-emptive treatment was equally as effective as long term ganciclovir prophylaxis in high risk patients. Ganciclovir prophylaxis for 4 weeks appears ineffective in heart allograft recipients treated with antithymocyte globulin. Long term sequential intravenous/ oral ganciclovir therapy has shown greater efficacy in preventing CMV disease than sequential ganciclovir/aciclovir therapy. in these patients. Initial reports indicate that pre-emptive therapy may be beneficial in this patient group. although this remains to be determined. Ganciclovir in therapeutic dosage regimens generally has acceptable tolerability with adverse effects usually of a haematological or neurological nature. Neutropenia, thrombocytopenia and anaemia are the primary dose-limiting toxicities associated with ganciclovir therapy. Overall, neutropenia occurs less frequently with administration of oral ganciclovir than with intravenous ganciclovir. Monitoring of renal function is recommended as serum creatinine levels may rise during ganciclovir therapy. In addition, ganciclovir prophylaxis appears more cost effective than the majority of other currently available therapies for CMV with oral ganciclovir more cost effective than intravenous ganciclovir. In conclusion, it is unlikely that a single strategy will be able to be applied to all transplant patients for the prevention of CMV disease. An optimal strategy will probably be arisk-adapted approach. Prophylactic treatment with ganciclovir appears the best strategy to implement in high risk patients: oral ganciclovir formulations may be best employed where lower toxicity is required. Pre-emptive treatment with ganciclovir appears most efficacious in patients identified as lower risk or, in the case of BMT recipients, where lower toxicity may be desirable. Ganciclovir remains an important therapeutic option for the prevention and treatment of CMV disease in transplant recipients.

Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

“…We aimed at AUC values of at least 50 mg · h/liter and a trough concentration of at least 2 mg/liter in the present study to avoid underdosing in these patients with life-threatening CMV infection. Consistent with previous reports, serum concentrations in our study were elevated in comparison to those of patients with normal renal function (1,3,21,32). Gando et al reported elevated blood serum concentrations at the same dosage as we used (peak level of 11.8 mg/liter in our study, versus 20.3 mg/liter in the case report by Gando et al) (21).…”

“…Ganciclovir is an effective antiviral substance used for first-line treatment of CMV infections, which has a predominantly renal elimination (1,3,5,19). Although ganciclovir is often used in routine clinical practice, pharmacokinetic data for critically ill patients undergoing CRRT are rare and inconsistent.…”

“…However, there are no data for any dosing recommendations ensuring effective drug levels during therapy. The IC 50 , the concentration of the drug that is required for 50% inhibition has been reported, depending on the strain, to range from 0.3 to 2.8 mg/liter (3,8,28). It is known that appropriate dosing of ganciclovir is important to avoid clinical inefficacy and possible development of resistance (29).…”

“…It has a proven therapeutic effect in treatment of several CMV-related infections, such as retinitis, pneumonia, infections of the gastrointestinal tract, and infections of the nervous system, or prevention of CMV disease in patients with AIDS or an immunocompromised state following transplantation (1)(2)(3). The risk of CMV infection is increased in critically ill patients due to the requirement for mechanical ventilation, sepsis, immunodeficiency, transfusions, and renal failure (4).…”

“…The elimination of any given drug by continuous renal replacement therapy (CRRT) is dependent on different factors such as specific properties of the membrane (pore size, filter surface area, adsorption, and filter material), characteristics of the CRRT technique used (blood flow rate and ultrafiltration rate), or properties of the drug (volume of distribution [V], molecular charge, molecular mass, and protein binding) (11,12). The low molecular mass of ganciclovir (255.2 Da), high water solubility (3 mg/ml), and very low plasma protein binding (1 to 2%) are relevant factors in removal via CVVHDF (3,7).…”