Ganciclovir: an update of its use in the prevention of cytomegalovirus infection and disease in transplant recipients.

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.