Doses Of Valaciclovir Research Articles

Different dosages of valaciclovir for the treatment of herpes zoster in adults: A randomized clinical study.

The dosages of valaciclovir used for herpes zoster treatment recommended by Chinese pharmaceutical companies can differ considerably from those reported in the literature. This randomized clinical study compares the efficacy and safety of different oral valaciclovir doses for the treatment of herpes zoster in adults. A total of 214 patients with herpes zoster were enrolled and randomized into two groups according to age: 98 patients in the 18-44-year group (younger patients) and 116 patients in the 45-74-year group (middle-aged and elderly patients). Patients in the two age groups were then prescribed different doses of valaciclovir. The high-dose group was administered 900mg of valaciclovir, three times daily for 10days, whereas the low-dose group was administered 300mg of valaciclovir, two times daily for 10days. The efficacy and side effects of these regimens were recorded on days 6, 11 and 30. In total, 207 (of 214 enrolled) patients completed the study. Of the seven patients who discontinued the study, five discontinued because their follow-up time was not fixed and two withdrew after moving to other cities. At the 11th day after treatment, the clinical effect of high-dose valaciclovir groups were significantly better than that of the low-dose valaciclovir groups in middle-aged and elderly patients (p<0.05). The difference in visual analog scale (VAS) pain scores between the two dose groups was statistically significant in middle-aged and elderly patients at the 6th day(p<0.05), whereas there was no difference in younger patients (p>0.05). The VAS scores were significantly lower in high-dose group than in low-dose group at day 11 in both groups of patients(p<0.05).There was no statistically significant difference in the time to skin scab improvement between the two different dose groups in younger patients (p>0.05). Among middle-aged and elderly patients, the incidence of postherpetic neuralgia (PHN) was significantly lower in the high-dose group than in the low-dose group (p<0.05). The difference in the incidence of adverse reactions between the high-dose and low-dose groups was not statistically significant (p>0.05). Overall, the main side effect was headache. The present study indicates that early treatment with high-dose valaciclovir can significantly reduce pain in patients, especially in elderly patients, in whom it can also reduce the incidence of PHN. In terms of safety, no significant difference was noted in the incidence of adverse reactions between high- and low-dose groups.

Hospital risk management of cutaneous herpes simplex virus infection.

The epidemiology of cutaneous herpes simplex infection (CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear. To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir. The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score (AES). Safety was characterized as the proportion of patients with drug adverse reactions (DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference (SMD) and risk ratio (RR), respectively. Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = -0.73 (95% CI -0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002). Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored.

Low‐dose valaciclovir and cytomegalovirus immunoglobulin to prevent cytomegalovirus disease in high‐risk renal transplant recipients

Cytomegalovirus (CMV) remains an important cause of disease in renal transplant recipients. Prophylaxis is effective in reducing disease; however, the optimal regimen remains uncertain. We assessed the efficacy of low-dose valaciclovir (3 months) and intravenous CMV immunoglobulin in the prevention of CMV disease in CMV-negative recipients of kidneys from CMV-positive donors (D+/R-). A single-centre, retrospective study examining the incidence of CMV disease and patient and graft survival in all patients transplanted between October 2000 and November 2004. Among 203 renal transplant recipients, 46 were D+/R- (22.7%) and received prophylaxis. Of the 203 recipients, 21 (10.3%) developed CMV disease over a four-year follow-up period. Within the D+/R- group, CMV disease occurred in 15.2% of patients at 6 months (7/46), and 21.7% at 4 years (10/46). Of the 10 D+/R- patients who developed CMV disease, six were inadvertently on a dose of valaciclovir below that dictated by protocol arising from a failure to increase dosage in parallel with improving recipient renal function. In the D+/R- recipients where the protocol was adhered to, the incidence of CMV disease was 5% (2/40) at 6 months, and 10% (4/40) at 4 years. Low-dose valaciclovir with CMV immunoglobulin was as efficacious in preventing CMV disease as other published regimens, including those with full-dose valaciclovir and valganciclovir. There was a low incidence of CMV disease beyond 6 months. Outcomes could be improved by ensuring appropriate dose adjustment following changes in renal function.

Interventions for prevention and treatment of herpes simplex virus in cancer patients

Relevant data was sourced using the Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, CANCERLIT, SIGLE and LILACS. Searching by hand was also carried out, reference lists checked for further trials, and authors and known specialists in the field contacted to try to identify any additional published or unpublished trials. Randomised controlled trials that concerned treatment or prophylaxis of orofacial lesions [caused by herpes simplex virus (HSV)] in adults, children (or both) who were immunocompromised because of cancer were eligible for inclusion. Outcomes of interest were presence/ absence of clinical/ culture-positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life, and adverse effects. The reports obtained from the electronic and other forms of searches were assessed independently by the review authors. Disagreements were resolved by discussion and reasons recorded. Authors were contacted for details of randomisation, blindness and sample demographics. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaborations statistical guidelines were followed and risk ratio values were calculated using random effects models. In the 17 trials, three interventions were studied: use of aciclovir, valaciclovir and prostaglandin E. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life. In the placebo-controlled trials, aciclovir was found to be effective for prevention and treatment. In comparisons of active interventions, there is no evidence of a significant difference in efficacy between valaciclovir and aciclovir, or higher doses of valaciclovir and lower doses. In the single study assessing the effectiveness of prostaglandin E for prevention, this intervention was less effective than placebo. No adverse effects were reported. There is evidence that aciclovir is effective at preventing and treating HSV infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that, as a prophylaxis, placebo is more efficacious than prostaglandin E. In all included trials the risk of bias was unclear.

Interventions for the prevention and treatment of herpes simplex virus in patients being treated for cancer

Treatment of cancer is increasingly effective, but associated with oral complications such as mucositis, fungal infections, bacterial infections and viral infections such as the herpes simplex virus (HSV). To examine the effects of interventions for the prevention or treatment or both, of herpes simplex virus in patients receiving treatment for cancer. We searched the following databases: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, CANCERLIT, SIGLE and LILACS. The reference list of all related review articles and articles considered to be potentially relevant were checked for further trials. Authors of identified trials and known specialists in the field were also contacted in an attempt to identify any additional published or unpublished trials. Date of most recent search: November 2008. All randomised controlled trials comparing interventions for the prevention or treatment or both of HSV infection in people being treated for cancer. Outcomes were presence/absence of clinical/culture positive HSV infections (prevention), time to complete healing of lesions (treatment), duration of viral shedding, recurrence of lesions, relief of pain, amount of analgesia, duration of hospital stay, cost of oral care, patient quality of life and adverse effects. Data were independently extracted, in duplicate, by two review authors. Authors were contacted for details of randomisation, blindness and sample demographics where necessary. Quality assessment was carried out on randomisation, blindness, withdrawals and selective reporting. The Cochrane Collaboration's statistical guidelines were followed and risk ratio (RR) values were calculated using random-effects models. Seventeen trials satisfied the inclusion criteria. Four trials evaluated preventative interventions for HSV lesions, three trials for viral isolates, and eight trials evaluated both outcome measures. A single trial reported on the cost of prophylaxis for HSV. Two trials evaluating treatment reported on time to healing, duration of viral shedding and relief of pain. No trials reported on duration of hospital stay, amount of analgesia or patient quality of life.In placebo controlled trials, aciclovir was found to be effective for the prevention of HSV infections as measured by oral lesions or viral isolates (RR = 0.16, 95% confidence interval (CI) 0.08 to 0.31 nine trials; RR = 0.17, 95% CI 0.07 to 0.37 nine trials). There is no evidence that valaciclovir is more efficacious than aciclovir, or that higher doses of valaciclovir are more effective than lower doses. Placebo was found to be more effective than prostaglandin E for prevention of viral isolates (RR = 1.87, 95% CI 1.12 to 3.14 one trial).Aciclovir was also found to be effective for the treatment of HSV in terms of duration of viral shedding (median of 2.5 days versus 17.0 days, P = 0.0002; 2 days compared to more than 9, P = 0.0008), time to first decrease in pain (median 3 days compared to 16, P = 0.04), complete resolution of pain (9.9 days compared to 13.6 days, P = 0.01; median of 6 days compared to 16, P = 0.05), 50% healing (median of 6 days compared to 11, P = 0.01) and total healing (median 13.9 days compared to 20.7 days, P = 0.08; median of 8 days compared to 21, P = 0.0). There is evidence that aciclovir is efficacious in the prevention and treatment of herpes simplex virus infections. There is no evidence that valaciclovir is more efficacious than aciclovir, or that a high dose of valaciclovir is better than a low dose of valaciclovir. There is evidence that as a prophylaxis, placebo is more efficacious than prostaglandin E. However, in all included trials, risk of bias is unclear.

A large-scale, placebo-controlled, dose-ranging trial of peroral valaciclovir for episodic treatment of recurrent herpes genitalis. Valaciclovir HSV Study Group

Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. We conducted a double-blind, placebocontrolled, patient-initiated clinical trial of peroral valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [Cl], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the valaciclovir groups were comparable with those of the placebo group. Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis.

A Large-Scale, Placebo-Controlled, Dose-Ranging Trial of Peroral Valaciclovir for Episodic Treatment of Recurrent Herpes Genitalis

<h3>Background:</h3> Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics. <h3>Methods:</h3> We conducted a double-blind, placebo-controlled, patient-initiated clinical trial of peroral valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers. <h3>Results:</h3> Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [CI], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcer-ative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the valaciclovir groups were comparable with those of the placebo group. <h3>Conclusions:</h3> Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis. Arch Intern Med. 1996;156:1729-1735

Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single-and multiple-dose administration to normal volunteers

The pharmacokinetics and safety of the L-valyl ester pro-drug of acyclovir, valaciclovir (256U87), were investigated in two phase I, placebo-controlled trials in normal volunteers. These included a single-dose study with doses from 100 to 1000 mg (single cohort) and a multiple-dose investigation with doses from 250 to 2000 mg (five separate cohorts). In each cohort, eight subjects received valaciclovir and four subjects received placebo. Pharmacokinetic findings for valaciclovir and acyclovir were consistent in the two studies. Valaciclovir was rapidly and extensively converted to acyclovir, resulting in significantly greater acyclovir bioavailability (approximately threefold to fivefold) compared with that historically observed with high-dose (800 mg) oral acyclovir. At the higher valaciclovir doses, acyclovir maximum concentration and daily area under the concentration-time curve approximated those obtained with intravenous acyclovir. The favorable safety profile and enhanced acyclovir bioavailability from valaciclovir administration has prompted additional clinical evaluations for zoster and herpes simplex virus treatment, as well as cytomegalovirus suppression in immunocompromised patients.

Valaciclovir (BW256U87): the L-valyl ester of acyclovir.

Valaciclovir (BW256U87) is an L-valyl ester of acyclovir, which is extensively and almost completely converted to acyclovir. In healthy human volunteers, single valaciclovir doses of 100-1000 mg resulted in dose-proportional increases in acyclovir area under the curve (AUC). The 1,000 mg dose produced an acyclovir peak plasma concentration (Cmax) of 5-6 micrograms/ml, AUC6 of 19 hr. micrograms/ml, time to maximum plasma concentration (Tmax) of 1-2 hr, and half-life (T1/2) of 2.8 hr. Plasma valaciclovir peak levels were < 0.3 micrograms/ml, and the prodrug was undetectable after 3 hr. Multiple valaciclovir doses of 250-2,000 mg given four times daily for 10 days resulted in dose-proportional increases in acyclovir Cmax. There were less than proportional increases in the AUCs. No serious or unexpected adverse events or laboratory abnormalities were reported. In volunteers with advanced human immunodeficiency virus (HIV) disease (absolute CD4 lymphocyte count < 150 cells/microliters), acyclovir and valaciclovir pharmacokinetic results were nearly identical to those in healthy volunteers. At the 2 g dose administered four times daily, steady-state acyclovir Cmax = 8.4 micrograms/ml, Tmax = 2.0 hr, AUC6 = 30.5 hr. micrograms/ml, and T1/2 = 3.3 hr. Nausea, vomiting, diarrhoea, and abdominal pain were commonly reported; however, only one adverse event (diarrhoea) was causally linked to valaciclovir exposure. There were no renal or neurologic adverse events. Valaciclovir is well absorbed and is rapidly converted to acyclovir, resulting in three- to fourfold higher acyclovir levels than can be achieved with oral acyclovir, even in patients with advanced HIV disease. The safety profile is generally favourable, with no evidence of nephrotoxicity or neurotoxicity.