Antiviral dosing and efficacy for prophylaxis of cytomegalovirus disease in solid organ transplant recipients
University of Chicago Hospitals, 5841 South Maryland Avenue, Mail Code 5026, Chicago, IL 60637, USA. American Journal of Health-System Pharmacy
(Impact Factor: 1.88).
11/2006; 63(19 Suppl 5):S17-21. DOI: 10.2146/ajhp060379
The implications of the findings from clinical studies and pharmacokinetic analyses of the antiviral agent valganciclovir for dosing of the drug to prevent cytomegalovirus (CMV) disease in solid organ transplant recipients are reviewed.
Valganciclovir, an oral prodrug of ganciclovir, is as effective as oral ganciclovir for preventing CMV disease, although prophylaxis with either agent may delay CMV disease. Dosage reduction is required for both drugs in patients with renal impairment to prevent high plasma ganciclovir concentrations and toxicity. A valganciclovir dosage of 900 mg/day is required in patients with normal renal function, especially those at high risk for CMV disease, to provide adequate systemic ganciclovir exposure. Some studies suggest that a lower dosage might suffice for patients at a low risk for CMV disease.
Valganciclovir dosing should be based on renal function to avoid toxicity.
Available from: gla.ac.uk
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ABSTRACT: Outbreaks and sporadic cases of viral Infectious Intestinal Disease (IID) are a major public health issue resulting in significant morbidity and sometimes mortality each year. The economic costs associated are substantial. Laboratory diagnosis of viral IID is important as the many infectious and non-infectious causes cannot be reliably differentiated using clinical or epidemiological characteristics alone. An accurate diagnosis can aid patient management, infection control procedures and reduce health care costs by preventing unnecessary treatments, testing for alternative causes and hospital stay. It also aids public health surveillance. At the start of the research described in this thesis the West of Scotland Specialist Virology Centre (WOSSVC) used Electron Microscopy (EM) as the frontline test for outbreaks and sporadic cases of IID. However, although rapid on a small number of samples, this technique has been shown to be insensitive, laborious and is not suited to testing large numbers of samples. The research presented in this thesis sought to examine whether molecular diagnostic techniques such as conventional gel-based or real-time Polymerase Chain Reaction (PCR) assays could be a viable replacement for EM as the frontline test(s) for viral IID in a routine laboratory service of this type, and whether their implementation could bring benefits to the laboratory service in terms of improved rapidity, sensitivity and throughput. The aim was to adapt published PCR methods for use in routine diagnostic work rather than for research purposes, an approach that distinguishes this research from previous work in this area. In order to achieve this aim, the appropriate PCR techniques were first selected from the literature, based on a combination of clinical and laboratory requirements, and were adapted for use in the laboratory service. A series of laboratory experiments was then carried out in order to compare the sensitivity of the adapted methods to existing techniques such as EM and antigen detection assays (EIAs) and to other methods that emerged during the period of study including alternative PCR assays. Where found to be suitable, the selected PCR tests were implemented in the routine diagnostic service for viral IID. The effects of these changes on the laboratory service were then examined. The results show that since the introduction of molecular tests at WOSSVC for the detection of viral pathogens in cases of gastroenteritis the number of samples tested has risen steadily, as have the detection rates for each of the main viral causes of IID. Furthermore, this has been achieved at the same time as a substantial reduction in sample turn-around-times. Such improvements will have a positive impact in several areas of public health relating to viral IID and are discussed fully, including patient management, infection control and national surveillance.
Available from: roche-trasplantes.com
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ABSTRACT: Valganciclovir has widely become the agent of choice for the prevention of cytomegalovi-rus in recipients of organ transplants. Optimal dosing is needed to achieve efficacy and avoid toxicity. For subjects at high risk of cytomegalovirus, it is strongly suggested that full-dose (based on renal function) valganciclovir be used. While low-dose valganciclovir appears to be efficacious in some reports, the recommendations are based on inadequate-ly designed trials and must be taken with caution. Unfortunately, because of the sample size needed, it is not likely that the efficacy of reduced-dose valganciclovir will be ade-quately tested in well-controlled trials. The duration of prophylaxis, particularly whether prophylaxis should be extended beyond three months, continues to be an important ques-tion and is the subject of a well-designed clinical trial of which we anxiously await the results.
Available from: aop.sagepub.com
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ABSTRACT: To review the pharmacology, pharmacokinetics, efficacy, and safety of maribavir, a novel antiviral agent in the benzimidazole drug class.
Articles were identified through searches of MEDLINE (January 1998-July 2008). Abstracts from recent scientific meetings and the manufacturer were also included.
All English-language in vitro and in vivo studies and abstracts evaluating maribavir were reviewed and considered for inclusion. All human studies were included.
Maribavir has significant activity against both human cytomegalovirus (CMV) and Epstein-Barr virus, but not other herpesviruses. Unlike ganciclovir, which needs to be phosphorylated by UL 97 kinase to become an active inhibitor of DNA polymerase, maribavir directly inhibits UL 97 kinase. UL 97 kinase is an early viral gene product involved in viral DNA elongation, DNA packaging, and egress or shedding of capsids from viral nuclei. Maribavir has also been found to be effective against ganciclovir-resistant CMV strains. Maribavir differs from current CMV antiviral agents in its adverse event profile. Maribavir is not associated with nephrotoxicity or hematologic toxicities, but has been associated with taste disturbances. In February 2007, maribavir was granted Food and Drug Administration orphan drug status for prevention of CMV viremia and diseases in at-risk populations. Maribavir Phase 2 trials in stem-cell transplant recipients have been completed, and there are ongoing Phase 3 trials in stem-cell and organ transplant recipients.
Maribavir may be an option for treatment of ganciclovir-resistant CMV infections. Its bioavailability is greater than that of oral ganciclovir, but less than that of valganciclovir. No differences in pharmacokinetics were seen in renally impaired patients, although dialysis-dependent patients were not evaluated. Maribavir is not associated with hematologic toxicities; however, the high prevalence of taste disturbances may limit its tolerability.
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