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At least 397 records · Page 22Linked to original sources
PubMed1998

Cost effectiveness of newer antiviral agents for herpes zoster: is the evidence spotty?

Famciclovir and valaciclovir were approved for use in the treatment of herpes zoster despite controversy over antiviral therapy in zoster due to high costs and uncertain benefits. To explore these issues, a Markov decision model was developed, and the incremental cost effectiveness of antiviral treatment for herpes zoster was estimated using these agents compared with no antiviral therapy. A third-party payer perspective was taken. Sensitivity analyses were performed, modeling differences in antiviral efficacy, postherpetic neuralgia (PHN) risk, and other illness parameters. Treatment of severely symptomatic acute zoster was found reasonable from a cost-effectiveness standpoint in base-case and worst-case scenarios. Treatment of mildly symptomatic acute zoster was more expensive but would likely be considered cost effective in scenarios where PHN risk was higher, PHN duration longer, or antiviral shortening of PHN greater. Further research comparing antiviral efficacy in herpes zoster is needed.

2-Aminopurine↗
PubMed1998

Treatment of acute herpes zoster: effect of early (< 48 h) versus late (48-72 h) therapy with acyclovir and valaciclovir on prolonged pain.

The efficacy of early versus late treatment with acyclovir and valaciclovir on zoster-associated pain was assessed from two databases (1076 patients) that were compiled from randomized trials. Early treatment was started < 48 h and late treatment was started 48-72 h after the onset of cutaneous herpes zoster. Median times to complete resolution of zoster-associated pain were 28 and 62 days, respectively, for patients (> or = 18 years of age) treated with acyclovir and placebo within 48 h (hazard ratio [HR], 1.68; 95% confidence limit [95% CL], 1.19, 2.38) and 28 and 58 days, respectively, for those treated later (HR, 2.20; 95% CL, 1.03, 4.71). In the valaciclovir versus acyclovir study (in patients > or = 50 years of age), the corresponding figures were 44 and 51 days for patients treated early (HR, 1.28; 95% CL, 1.03, 1.60) and 36 and 48 days for those treated later (HR, 1.40; 95% CL, 1.04, 1.87). Acyclovir significantly shortened the time to complete resolution of zoster-associated pain compared with placebo (and valaciclovir was superior to acyclovir in this regard) even when therapy was delayed up to 72 h after rash onset.

Acute Disease↗
PubMed1998

Valaciclovir for the suppression of recurrent genital herpes simplex virus infection: a large-scale dose range-finding study. International Valaciclovir HSV Study Group.

A randomized, double-blind study of valaciclovir for suppression of recurrent genital herpes was conducted among 1479 immunocompetent patients. Patients were randomized to receive valaciclovir (250 mg, 500 mg, or 1 g once daily, or 250 mg twice daily), acyclovir (400 mg twice daily), or placebo, for 1 year. All valaciclovir dosages were significantly more effective than placebo at preventing or delaying recurrences (P < .0001). There was a dose-response relationship (P < .0001) across the once-daily valaciclovir regimens. Twice-daily valaciclovir and acyclovir were similar in effectiveness. Subgroup analysis showed that patients with a history of < 10 recurrences per year were effectively managed with 500 mg of valaciclovir once daily. One gram of valaciclovir once daily, 250 mg of valaciclovir twice daily, or 400 mg of acyclovir twice daily were more effective in patients with > or = 10 recurrences per year. Safety profiles of all treatments were comparable. Thus, valaciclovir is highly effective and well tolerated for suppression of recurrent genital herpes. Once-daily regimens offer a useful option for patients who require suppressive therapy for management of genital herpes.

Acyclovir↗
PubMed1996

Differential effects of famciclovir and valaciclovir on the pathogenesis of herpes simplex virus in a murine infection model including reactivation from latency.

The ability of famciclovir and valaciclovir to affect the establishment and maintenance of latency in mice with a cutaneous herpes simplex type 1 (HSV-1) infection was examined. Mice were treated via drinking water starting at various times between days 1 and 5 and terminating on day 10 after inoculation. Clinical signs and viral replication in the target tissues were monitored. Three to four months later, trigeminal and dorsal root ganglia were explanted from groups of 16 mice and examined for latent virus by cocultivation. The two compounds differed in their effects on the acute neural infection, and ganglia explanted from famciclovir-treated mice were markedly reduced in their ability to reactivate virus, although neither drug affected latency if treatment was delayed for several months. The difference between the compounds is likely to reflect differences in the metabolism of their respective products, penciclovir and acyclovir, in infected neurons.

2-Aminopurine↗
PubMed1996

Lack of interaction between valaciclovir, the L-valyl ester of acyclovir, and Maalox antacid.

Valaciclovir is rapidly and extensively converted to acyclovir. In this study we investigated the potential interaction between oral valaciclovir and Maalox. On each of three occasions 18 healthy volunteers received a single oral dose of 1000 mg valaciclovir, or 30 mL Maalox 65 min after valaciclovir administration, or 30 mL Maalox 30 min before valaciclovir. Acyclovir plasma concentrations and pharmacokinetic parameters were not significantly affected by administration of Maalox before or after valaciclovir. Therefore, there is no need for restriction of valaciclovir dosing in patients receiving antacid medication.

Acyclovir↗
PubMed1997

New therapeutic approaches to the alphaherpesvirus infections.

The character of diseases caused by alphaherpesviruses has changed over the last decade. The severity of disease and the frequency of acyclovir resistance has increased with the increase in the number of immunocompromised patients. Compounding the trend towards more virulent herpes disease is the current emphasis towards outpatient management of many diseases. Much of the current antiviral research focuses on providing drugs with (i) improved oral bioavailability and pharmacokinetics which permit less frequent oral or topical dosing for suppressive treatment of herpes simplex virus (HSV) infections, (ii) different mechanisms of action for synergic effects in treating resistant HSV infections in the immunocompromised host and (iii) improved efficacy. Future antiviral agents will probably target enzymes or viral factors essential for infection or will inhibit other steps in the viral infection cycle, such as viral entry, protein synthesis or capsid assembly. Medications that augment the immune response constitute another pathway for combating herpes viral infections. Many of the newer experimental agents target essential processes unique to herpesvirus replication and, therefore, potentially have high selectivity.

2-Aminopurine↗
PubMed2001

Comparable aciclovir exposures produced by oral valaciclovir and intravenous aciclovir in immunocompromised cancer patients.

The objective of this study was to evaluate the comparability of systemic aciclovir exposure at steady state in immunocompromised patients following oral valaciclovir 1000 mg tds and intravenous (iv) aciclovir 5 mg/kg tds. A two-centre, randomized, open label, two-way crossover study was undertaken. Patients aged 18-65 years who had undergone high-dose chemotherapy for cancer and were neutropenic (neutrophil count <0.5 x 109/mL) with normal renal function were recruited. The pharmacokinetic parameters of aciclovir after oral valaciclovir 1000 mg or iv aciclovir 5 mg/kg given as 1 h infusion, each administered every 8 h for seven doses, were compared. Fifteen patients were enrolled and 13 completed both treatments. The mean (s.d.) values for aciclovir after oral valaciclovir and iv aciclovir were: AUC0-8 76.3 (29.7) and 64.2 (20.0) microM x h; peak plasma concentration (Cmax) 26.6 (10.5) and 34.0 (11.9) microM; time to maximal plasma concentration (tmax) 2.01 (0.65) and 0.95 (0.19); and plasma elimination half-life (t1/2) 2.83 (0.91) and 2.44 (0.62) h, respectively. The mean absolute bioavailability of aciclovir from oral valaciclovir was 60 +/- 21%. Equivalent systemic exposure to aciclovir after oral valaciclovir 1000 mg and iv aciclovir 5 mg/kg was observed with AUC0-8 (oral/iv ratio = 1.16; 90% CI 0.98-1.39), whilst significantly reduced peak aciclovir concentrations were obtained with oral valaciclovir (ratio = 0.75; 90% CI 0.60-0.94). Oral valaciclovir offers a convenient, and possibly safer, alternative to iv aciclovir, delivering comparable systemic exposures with reduced peak levels. This may contribute to shorter hospitalization, reduced costs for healthcare providers and improved quality of life for patients.

Acyclovir↗
PubMed2004

Clinical significance of antiviral therapy for episodic treatment of herpes labialis: exploratory analyses of the combined data from two valaciclovir trials.

Valaciclovir (Valtrex) 2 g twice daily for 1 day was recently approved in the United States for treatment of cold sores. In order to apply more clinically relevant assumptions to the analysis, we examined the effect of different missing data and endpoint assumptions on apparent valaciclovir efficacy. Results of each analysis demonstrate statistically significant increases in the proportion of subjects whose cold sores were aborted with valaciclovir compared with placebo, and significant decreases in healing times for subjects with cold sore lesions who were treated with valaciclovir compared with placebo. These exploratory analyses provide evidence of the robustness of the results to differing missing data assumptions and show that use of more clinically relevant endpoint assumptions increases the magnitude of some therapeutic responses. We also introduce a new measure that combines the two observed drug effects (reduced lesion duration, increased aborted lesions) into a single endpoint that captures the global benefit of the drug to the patient.

Acyclovir↗
PubMed2004

Pharmacokinetics of valaciclovir.

While active against Herpesviridae, oral aciclovir is limited by low and inconsistent bioavailability. Modification of aciclovir by valine esterification, producing valaciclovir, results in significant increases in systemic aciclovir plasma levels. The exact mechanism of increased absorption with valaciclovir is not fully determined but probably involves intestinal dipeptide transporters, followed by rapid ester hydrolysis in the small intestine and liver. The enhanced pharmacokinetics of valaciclovir have translated into improvements in clinical efficacy and patient convenience.

Acyclovir↗
PubMed2006

The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment.

OBJECTIVES: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy. METHODS: We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis. RESULTS: CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 micromol/L, range 0.6-7.0). The concentration of CMMG was below the limit of quantification (<0.5 micromol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure. CONCLUSIONS: These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.

Acyclovir↗
PubMed2003

Efficacy and safety of lowering immunosuppression to treat CMV infection in renal transplant recipients on valaciclovir prophylaxis: a pilot study.

BACKGROUND: Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis. METHODS: We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. RESULTS: The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. CONCLUSION: The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.

Acyclovir↗
PubMed2006

Adverse neuropsychiatric effects of cytomegalovirus prophylaxis with valaciclovir in renal transplant recipients.

BACKGROUND: Valaciclovir (VACV) has been reported to induce adverse neuropsychiatric effects (ANE), especially in patients with renal failure, but few data are available for renal transplant recipients (RTR). METHODS: We conducted a retrospective study in RTR given VACV as cytomegalovirus prophylaxis, from January 1999 to December 2000, to define the incidence rate, type and outcome of VACV-induced ANE, and to identify risk factors for ANE. The VACV-induced ANE were defined as neuropsychiatric disorders justifying VACV dose reduction or withdrawal. Patients with and without VACV-induced ANE were compared by univariate and multivariate analysis. RESULTS: In all, 167 RTR were included, of whom 25 (15%) displayed VACV-induced ANE (mainly hallucinations and confusion), which occurred with a mean of 4 days after the start of VACV. ANE were reversible in all cases. Multivariate analysis showed that delayed graft function (DGF) was the main risk factor for VACV-induced ANE [Odds ratio (OR): 12.1; 95% CI = 3.4-43.4; P = 0.0001]. All VACV doses given to patients with ANE were in accordance with the current recommended adaptation to estimated glomerular filtration rate (GFR). CONCLUSION: In RTR, VACV-induced ANE are significantly frequent but reversible. DGF occurrence is the main risk factor for these ANE. In RTR with DGF, the recommended doses for GFR below 10 ml/min might be too high. Several strategies, in RTR with DGF, might lower the risk of ANE, including reduction of the currently recommended VACV dosage, delayed VACV introduction until improvement of renal function, or use of another anti-cytomegalovirus drug.

Acyclovir↗