American Journal of Health-System Pharmacy

Lake, Kathleen, D.

doi: 10.1093/ajhp/60.suppl_8.S13pmid: 14686230

The pharmacology, pharmacokinetics, safety, and efficacy of valganciclovir, an oral prodrug for ganciclovir, used to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are described. Valganciclovir was developed to overcome the disadvantages associated with ganciclovir, which include low oral bioavailability, limited efficacy because of the development of viral resistance, and the need for frequent administration, which can adversely affect patient adherence. Valganciclovir is rapidly converted to ganciclovir; systemic exposure to the parent drug is low and short in duration. The oral bioavailability of ganciclovir from valganciclovir is 10 times higher than that from the original ganciclovir formulation. Food increases the oral bioavailability of valganciclovir. In a four-way, randomized, crossover pharmacokinetic study of 28 liver transplant recipients, single doses of valganciclovir 900 mg and intravenous ganciclovir 5 mg/kg resulted in a similar ganciclovir systemic exposure. The systemic exposure was proportionately lower with a single 450-mg dose of valganciclovir but similar to that of oral ganciclovir 3 g administered in three divided doses. In the recent multicenter, randomized, double-blind, double-dummy PV16000 trial in 364 solid organ transplant recipients at high risk for CMV disease (i.e., CMV-negative recipients of CMV-positive donor organs), valganciclovir 900 mg once daily was as effective in preventing CMV-disease as oral ganciclovir 1 g three times daily. Resistance was reported with ganciclovir but not with valganciclovir. Both drugs were well tolerated. Antivirals, Cytomegalovirus infections, Drug interactions, Drugs, availability, Drugs, Food, Ganciclovir, Pharmacokinetics, Resistance, Toxicity, Transplantation, Valganciclovir This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 10, 2002, during the ASHP Midyear Clinical Meeting, Atlanta, GA, and supported by an unrestricted educational grant from Roche Pharmaceuticals. Dr. Lake received an honorarium for participating in the symposium. Copyright © 2003 by American Society of Health-System Pharmacists

Schnitzler, Mark, A.

doi: 10.1093/ajhp/60.suppl_8.S5pmid: 14686228

The impact of prophylactic oral ganciclovir therapy on the incidence of cytomegalovirus (CMV) disease, patient and graft survival, and costs in patients receiving kidney and liver transplants is described. CMV disease is a common cause of morbidity and mortality in solid organ transplant recipients unless prophylactic drug therapy is used. Prophylactic oral ganciclovir therapy reduces the incidence of CMV disease in kidney and liver transplant recipients. It is more effective for recipients who are seronegative before the transplant and receive organs from seronegative (D-/R-) donors than in seronegative recipients of organs from seropositive (D+/R-) donors. CMV disease remains a problem in the latter. CMV disease increases the risk of graft failure, which decreases the likelihood of patient survival. The extent of matching of the DR subregion of the human leukocyte antigen complex in the donor and recipient may affect graft survival in patients with CMV disease. Graft failure is costly and should be considered in economic analyses of CMV prophylaxis regimens because of the potential impact of prophylaxis on CMV disease. The use of oral ganciclovir for CMV prophylaxis has reduced the incidence of CMV disease in kidney and liver transplant recipients. Antivirals, Costs, Cytomegalovirus infections, Economics, Ganciclovir, Graft rejection, Mortality, Transplantation This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 10, 2002, during the ASHP Midyear Clinical Meeting, Atlanta, GA, and supported by an unrestricted educational grant from Roche Pharmaceuticals. Dr. Schnitzler received an honorarium for participating in the symposium. Copyright © 2003 by American Society of Health-System Pharmacists

Pescovitz, Mark, D.

doi: 10.1093/ajhp/60.suppl_8.S3pmid: 14686227

This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 10, 2002, during the ASHP Midyear Clinical Meeting, Atlanta, GA, and supported by an unrestricted educational grant from Roche Pharmaceuticals. Dr. Pescovitz received an honorarium for participating in the symposium. He also receives clinical trial grants from Roche and is an ad hoc advisor to Roche. Copyright © 2003 by American Society of Health-System Pharmacists

Pescovitz, Mark, D.

doi: 10.1093/ajhp/60.suppl_8.S17pmid: 14686231

Four types of therapeutic strategies for managing cytomegalovirus (CMV) in solid organ transplant recipients, the mechanisms of action and efficacy of drugs used for prophylaxis, and the criteria for evaluating drugs for inclusion in a formulary are described. Universal and selective prophylaxis are simple to implement and effective for CMV prophylaxis, but they are costly and patient nonadherence and viral resistance can develop. Preemptive therapy may cause less resistance and cost less, but it is more complex and associated with a higher incidence of infection, which may have no effect on secondary effects from CMV infection, and higher recurrence of disease than prophylactic therapy. Treatment of active disease may be less costly for the drug than other approaches, but intravenous access is required and the rates of infection recurrence and mortality are higher compared with prophylaxis and preemptive therapy. Criteria for deciding which CMV prophylactic drugs to include in a formulary include efficacy, safety, convenience, and cost. CMV immune globulin i.v. is costly and exhibits reduced efficacy when used alone in patients at high risk for CMV disease. Intravenous ganciclovir is effective, but it is costly because of infusion costs. Intravenous drug therapies are inconvenient and associated with a risk of bacterial and fungal infection. Oral acyclovir is safe to use and inexpensive (since a genetic exists), but it has poor efficacy and is inconvenient because of the need for four large daily doses. Valacyclovir is more convenient and with similar safety and probably better efficacy than acyclovir, but it is more costly. Oral ganciclovir and oral valganciclovir have similar safety and costs, with greater efficacy than acyclovir. The single daily dose and lack of resistance to valganciclovir are advantages over oral ganciclovir, which requires three daily doses and can result in the development of resistance. Acyclovir, Antivirals, Costs, Cytomegalovirus immune globulin, Cytomegalovirus infections, Decision making, Dosage schedules, Drugs, Economics, Formularies, Ganciclovir, Mechanism of action, Mortality, Resistance, Toxicity, Transplantation, Valacyclovir, Valganciclovir This content is only available as a PDF. Author notes The assistance of Alice A. Kraman, Pharm.D., and Laura L. Hardwick, Pharm.D., is acknowledged. Based on the proceedings of a symposium held December 10, 2002, during the ASHP Midyear Clinical Meeting, Atlanta, GA, and supported by an unrestricted educational grant from Roche Pharmaceuticals. Dr. Pescovitz received an honorarium for participating in the symposium. Copyright © 2003 by American Society of Health-System Pharmacists

Troy Somerville,, K.

doi: 10.1093/ajhp/60.suppl_8.S9pmid: 14686229

Cost advantages of the oral route of drug therapy administration over the intravenous route for managing cytomegalovirus (CMV) disease are described. The overall costs usually are lower for the oral route of administration than for the intravenous route, although the cost to the patient depends on insurance coverage. Other advantages of the oral route include greater safety and convenience, which may improve patient adherence and quality of life. In patients with acquired immunodeficiency syndrome (AIDS), the use of oral ganciclovir instead of intravenous ganciclovir to treat the maintenance phase of CMV retinitis reduced the incidence of neutropenia and sepsis, outpatient and inpatient resource use, and costs. Oral therapy also improved patient quality of life. A cost-effectiveness model for liver transplant recipients found that CMV prophylaxis is warranted for all patients, ganciclovir is preferred over CMV immune globulin i.v. and oral acyclovir for prophylaxis, and the oral route of administration is more cost-effective than the intravenous route for ganciclovir. Valganciclovir, the oral prodrug of ganciclovir, was not included in this model. Oral maintenance therapy is usually cost-effective, safer, and more convenient than intravenous therapy in the management of CMV. Acquired immunodeficiency syndrome, Antivirals, Compliance, Costs, Cytomegalovirus infections, Drug administration routes, Economics, Ganciclovir, Patients, Quality of life, Toxicity, Transplantation This content is only available as a PDF. Author notes Based on the proceedings of a symposium held December 10, 2002, during the ASHP Midyear Clinical Meeting, Atlanta, GA, and supported by an unrestricted educational grant from Roche Pharmaceuticals. Dr. Somerville received an honorarium for participating in the symposium. Copyright © 2003 by American Society of Health-System Pharmacists