Valacyclovir Research Articles

Incidence of Postherpetic Neuralgia After Combination Treatment With Gabapentin and Valacyclovir in Patients With Acute Herpes Zoster

To evaluate the efficacy of treatment with gabapentin plus valacyclovir hydrochloride for the prevention of postherpetic neuralgia in patients with acute herpes zoster. Uncontrolled, open-label study. A private dermatology clinic. Consecutive immunocompetent adults (age, ≥ 50 years) who presented with herpes zoster within 72 hours of vesicle formation with moderate to severe pain (≥ 4 on the 10-point Likert scale) were recruited for study participation. Intervention The patients received 1000 mg of valacylovir hydrochloride 3 times a day for 7 days plus gabapentin at an initial dose of 300 mg/d, titrated up to a maximum of 3600 mg/d, side effects permitting. Proportion of patients with zoster pain (pain > 0) at 3, 4, and 6 months as well as average pain severity, the proportion of patients with sleep disturbance, and quality-of-life measures (determined by the Medical Outcome Study Short Form 36-Item Health Survey). A total of 133 patients (mean age, 64.6 years) were enrolled in the study. The overall incidence of zoster pain at 6 months was 9.8%. The combination of gabapentin and valacyclovir administered acutely in patients with herpes zoster reduces the incidence of postherpetic neuralgia. Trial Registration clinicaltrials.gov Identifier: NCT01250561.

A Concise Route to Valacyclovir Hydrochloride

AbstractAn efficient and concise synthesis of valacyclovir hydrochloride (4), which is a prodrug of acyclovir (3) is described. The synthesis was accomplished in two stages by coupling acyclovir with (2S)‐2‐azido‐3‐methylbutanoic acid followed by reduction (Scheme 2).

Valacyclovir neurotoxicity can be effectively managed by hemodialysis

Valacyclovir neurotoxicity can be effectively managed by hemodialysis

One-year low-dose valacyclovir as prophylaxis for varicella zoster virus disease after allogeneic hematopoietic stem cell transplantation. A prospective study of the Japan Hematology and Oncology Clinical Study Group

Varicella zoster virus (VZV) disease is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). We carried out a trial of 1-year low-dose valacyclovir (VCV) prophylaxis against VZV disease to evaluate its efficacy and safety. Patients received oral acyclovir (ACV) 1000mg/day until day 35 after HSCT. Oral VCV 500mg/day, 3 times a week, was started on day 36 and continued until 1 year after HSCT. The development of VZV disease was monitored until 2 years after HSCT. A total of 40 patients with a median age of 43 years were enrolled. VCV was well tolerated in all but 1 patient who discontinued it on day 224 because of thrombocytopenia of unknown cause. Seven patients developed VZV disease at a median of 479 days (range 145-651) after HSCT, with a cumulative incidence of 18.5%. Two patients developed breakthrough disease during VCV prophylaxis. The other 5 patients developed VZV disease after the discontinuation of VCV, and 3 of these had developed extensive chronic graft-versus-host disease. Visceral involvement and serious complications were completely eliminated. All patients responded to the therapeutic dose of VCV or ACV. One-year low-dose VCV can be safely and effectively administered for the prevention of VZV disease after allogeneic HSCT.

A randomized, double-blind, placebo-controlled trial of valacyclovir prophylaxis to prevent zoster recurrence from months 4 to 24 after BMT

Reactivation of latent VZV remains a significant cause of morbidity after SCT. Twenty-five percent or more of patients undergoing SCT will experience zoster within the first year after transplant. Short-course (<1 year) prophylaxis with acyclovir has been shown to be effective, but compliance with five times daily dosing may be problematic. We conducted a randomized, double-blind, placebo-controlled trial of valacyclovir (VACV) 1000 mg twice daily from 4 through 24 months after SCT for the prevention of VZV. Fifty-three VZV-seropositive transplant recipients (17 auto-SCT, 36 allo-SCT) were randomized at a median of 163 days after SCT. In a modified intent-to-treat analysis of 49 patients who took study drug, 0 of 22 in the VACV arm experienced zoster reactivation, compared with 6 of 26 (23%) in the placebo arm (P=0.025). Thirty-two subjects completed therapy through the second year post transplant or first episode of zoster. Adverse events resulting in discontinuation were more frequent in the placebo group (5 of 26 vs 3 of 27 for placebo and study drug, respectively). VACV at a dose of 1000 mg twice daily through 24 months after transplant is well tolerated and effective in suppressing shingles after SCT.

Effect of High versus Low Oral Doses of Valacyclovir on Herpes Simplex Virus-1 DNA Shedding into Tears of Latently Infected Rabbits

To assess the effect of high doses of valacyclovir (VCV) on HSV-1 DNA shedding into tears of latently infected rabbits. Three oral doses of VCV were tested. Corneas were inoculated with HSV-1, and latent infection was allowed to establish. Starting on postinoculation (PI) day 28, tear swabs were collected once daily for 6 consecutive days before treatment. The rabbits were placed in five balanced groups: group 1 had no treatment, group 2 received placebo, group 3 received 7 mg/kg VCV, group 4 received 70 mg/kg, and group 5 received 140 mg/kg. The treatment was administered by oral gavage twice daily, starting on PI day 36 and continuing for 14 days. The ocular swabs were collected beginning on PI day 40 and continuing for 10 days. The mean copy number of HSV-1 DNA before treatment was 370+/-70, 569+/-273, 368+/-86, 408+/-108, and 396+/-91, and the mean HSV-1 DNA copy number after treatment was 232+/-183, 564+/-186, 518+/-122, 67+/-63, and 13+/-7 in groups 1 to 5, respectively. There was no observable toxicity in any group. The 70- and 140-mg/kg doses of VCV significantly reduced the HSV-1 DNA copy number, compared with that of the other three groups. A daily dose of 500 mg (approximately 7 mg/kg) VCV in healthy human volunteers did not suppress HSV-1 DNA shedding in tears and saliva. Thus, higher doses of VCV may be necessary to reduce asymptomatic shedding in healthy human subjects.

High dose valacyclovir is highly effective to prevent cytomegalovirus and other herpes viruses viremia

High dose valacyclovir is highly effective to prevent cytomegalovirus and other herpes viruses viremia

Varicella Zoster Virus (VZV) in Solid Organ Transplant Recipients

-herpesvirus family. VZV is presentworldwide and is highly infectious. Primary infection leadsto acute varicella or ‘chickenpox,’ usually from exposureeither through direct contact with a skin lesion or throughairborne spread from respiratory droplets (1,2). After initialinfection, VZV establishes lifelong latency in cranial nerveanddorsalrootganglia,andcanreactivateyearstodecadeslater as herpes zoster (HZ) or ‘shingles’ (3). More than90% of adults in the United States acquired the disease inchildhood, while the majority of children and young adultshave been vaccinated with the live virus vaccine (2,4).Primary varicella typically presents with fever, constitu-tional symptoms and a vesicular, pruritic, widely dissem-inated rash that primarily involves the trunk and face (5).Thesymptomsusuallyresolvewithin7–10days,butinrarecases primary varicella leads to more severe disease andvisceral invasion. Complications, such as hepatitis, pancre-atitis, pneumonitis and encephalitis are infrequent but canbelife-threatening;adultsandveryyoungchildrenaremorelikely to develop such complications from primary infection(6,7). Rates of hospitalization and mortality due to varicellahave dropped with the institution of routine childhood vari-cella vaccination (8,9).Nearly all patients with HZ develop an exanthem of vesic-ular lesions in a dermatomal distribution. The annual inci-dence of HZ in the general population is 1.5–3.0 cases per1000 persons (2), and is estimated to occur in up to 20%of individuals during their lifetime (10). Secondary compli-cations such as bacterial superinfection and postherpeticneuralgia (PHN), or chronic neuropathic pain at the site ofHZ, lead to increased morbidity (11).Over 90% of adult solid organ transplant (SOT) recipientswill be seropositive for VZV. Rates are lower in pediatrictransplants(12,13),butimmunitywillincreaseasuptakeofvaricella vaccine improves. Varicella is rare in adult SOT re-cipients,butcanbedevastating,withvisceralinvolvement,severe skin disease, and disseminated intravascular coag-ulation (14–19). HZ is a frequent infectious complication inSOT recipients with an incidence of approximately 8–11%during the first 4 years posttransplant (20–22). Invasive dis-ease and dissemination similar to that seen in primary VZVinfection are uncommon but have been reported in SOTand other immunocompromised populations, and level ofimmunosuppression may alter the risk of developing thesecomplications (17,23,24). Rates of PHN in SOT recipi-ents may also be higher than in immunocompetent popu-lations (22).

Clinical observation of the herpes zoster with electric acupuncture,surrounding acupuncture and moxibustion with cotton

Objective To observe the clinical effect of electric acupuncture,surrounding acupuncture and cotton moxibustion in the treatment of herpes zoster.Methods Forty cases with herpes zoster were randomly divided into a treatment group and a control group,with 20 patients in each group.The treatment group was treated with electric acupuncture,surrounding acupuncture and cotton moxibustion,while the control group was treated with valaciclovir and vitamin B1.In the two groups severity of pain and the time of pain beginning to ease,pain lasting blisters disappearing,incrustation and decrustation during treatment were observed and recorded,referring to the People's Republic of China Traditional Chinese Medicine Industry Standard(Chinese disease diagnosis and efficacy standard)for efficacy evaluation.Results There was significant difference between the treatment group and the control group with regard to the cure rate(75% versus 35%,P＜0.05);however,the total effective rates of two groups had no significant difference(P＞0.05).After treatment VAS score in treatment group was significantly lower than that in control group(P＜0.05);in treatment group the time of pain beginning to ease and pain lasting were significantly less than those in control group(P＜0.05);the time of blister disappearing in treatment group was significantly faster than that in control group(P＜0.01);the time of incrustation and decrustation in treatment group were significantly less than those in control group(P＜0.05).Conclusion The advantages of electric acupuncture,surrounding acupuncture and cotton moxibustion in the treatment of herpes zoster were shown as faster pain easing,shorter pain lasting,shorter duration of blister and incrustation.This treatment for herpes zoster is safe,effective and affordable. Key words: Herpes zoster; Electric acupuncture; Surrounding acupuncture; Cotton Moxibustion

3007 Herpes zoster in solid tumor and hematologic malignancy patients – a cohort study in a managed care organization

The epidemiology of herpes zoster (HZ) in contemporary autologous hematopoietic cell transplant (HCT) recipients, and the impact of acyclovir (ACV)/valacyclovir (VACV) prophylaxis, is not well described. In this observational study from 2002 to 2010, we retrospectively identified 1000 varicella zoster virus (VZV)–seropositive autologous HCT recipients with up to 5 years of follow-up. The incidence of HZ and use of ACV/VACV prophylaxis were determined through review of medical records and mailed questionnaires. Risk factors for HZ were determined by multivariable Cox regression. Over a period of 5 years after autologous HCT, 194 patients developed at least 1 HZ episode, with a cumulative incidence of 21%; 159 of 194 (82%) were not on prophylaxis at the time of HZ. A second episode of HZ occurred in 31 of 194 (16%) patients. Patients taking ACV/VACV had reduced risk for HZ (adjusted hazard ratio [aHR], .59; 95% confidence interval [CI], .37 to .91), whereas those older than the median age (≥55.5 years) had increased risk (aHR, 1.42; 95% CI, 1.05 to 1.9). Disseminated VZV was reported in 8% and postherpetic neuralgia in 13% of patients. We demonstrate a high burden of HZ late after autologous HCT, despite long-term antiviral prophylaxis. Improved prevention strategies are needed to provide sustained protection against HZ after autologous HCT.

Incidence, Risk Factors, and Severity of Herpesvirus Infections in a Cohort of 121 Patients With Primary Dermatomyositis and Dermatomyositis Associated With a Malignant Neoplasm

Opportunistic infections have been reported in 15% to 21% of patients with inflammatory myositis. However, to our knowledge, no data are available regarding the incidence, risk factors, and severity of herpesvirus infections. Retrospective inception cohort study. Two departments in tertiary teaching hospitals. Patients All patients diagnosed as having dermatomyositis (DM) according to the criteria of Bohan and Peter seen during a 13-year period. Cumulative incidence rates of herpesvirus infections using the Kaplan-Meier method and risk factors for herpesvirus infections during the first year of DM using Cox proportional hazards models. A total of 121 patients met the inclusion criteria (mean [SD] age, 52 [15] years; 85 were women [70%]). Seventy-six percent had primary dermatomyositis, and 24% had dermatomyositis associated with a malignant neoplasm. The mean (SD) duration of follow-up was 42 (33) months. During follow-up, 20 patients developed a total of 22 herpesvirus infections (16 developed herpes zoster infections). The incidence rates for herpesvirus and for herpes zoster infections were 49 and 33 episodes per 1000 patient-years, respectively. In multivariate analysis, a positive association was noted between the risk of herpesvirus infection and use of systemic corticosteroid therapy (hazard ratio [HR], 3.71 [95% confidence interval {CI}, 1.02-13.41]; P = .04), lymphocyte count lower than 6000/microL (HR, 3.55 [95% CI, 1.00-12.65]; P = .05), and creatine phosphokinase level higher than 300 U/L (HR, 4.81 [95% CI, 1.28-18.06]; P = .02). Dermatomyositis associated with a malignant neoplasm tended to be negatively associated with the risk of herpesvirus infection (HR, 0.16 [95% CI, 0.02-1.29]; P = .08). The risk of serious herpesvirus infections in patients with DM is high. Educational strategies and studies evaluating the risk-to-benefit and the cost-to-benefit balances of a prophylaxis with valacyclovir hydrochloride in selected patients with DM are warranted.

Modalities to Decrease Stromal Herpes Simplex Keratitis Reactivation Rates

To evaluate the efficacy of adjunctive treatments to decrease herpes simplex keratitis (HSK) recurrences in patients with simultaneous stromal HSK and dry eye disease. This was a nonrandomized, single-center, retrospective, comparative analysis. Forty-two patients were diagnosed with unilateral HSK and dry eye disease. Of the 42 patients, 22 were treated with ipsilateral punctal occlusion by thermal cautery and 10 were treated with topical administration of cyclosporine, 0.05%, ophthalmic emulsion twice a day. Another group of 10 patients had previously undergone punctal occlusion and had cyclosporine ophthalmic emulsion twice a day added. All patients continued the use of oral acyclovir or valacyclovir hydrochloride and topical steroids. The frequency and duration of HSK recurrences were monitored for 1 year after initiation of treatment, and the rates were compared with those in the prior year. The thermal cautery and topical cyclosporine groups experienced HSK recurrences for mean durations of 7.1 and 5.8 mo/y before treatment, respectively, and these were reduced to 1.1 mo/y after treatment in both groups. Topical administration of cyclosporine further reduced the duration of HSK recurrences in patients with prior thermal cautery from an average of 1.3 mo/y before the addition of cyclosporine to 0.8 mo/y after the addition of cyclosporine. Permanent punctal occlusion by thermal cautery and the use of topical cyclosporine independently reduced recurrences of stromal HSK.

Incidence and Risk of Postherpetic Neuralgia after Varicella Zoster Virus Infection in Hematopoietic Cell Transplantation Recipients: Hokkaido Hematology Study Group

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.

Valacyclovir neurotoxicity: clinical experience and review of the literature

Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

Single-Day Famciclovir Found as Effective as 3-Day Valacyclovir

Single-Day Famciclovir Found as Effective as 3-Day Valacyclovir

Comparison of oral antiviral therapy with valacyclovir or acyclovir after penetrating keratoplasty for herpetic keratitis

Aims:To compare the outcome of prophylactic oral valacyclovir (VAL) or oral acyclovir treatment (ACV) in patients having undergone penetrating keratoplasty for herpetic keratitis (HK).Methods:All patients having received a penetrating keratoplasty...

Pharmacokinetics of valacyclovir in the adult horse

Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7-11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7-34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance liquid chromatography. Following the administration of 5 g VCV, the mean observed maximum serum ACV concentration (C(max)) was 1.45 +/- 0.38 (SD) microg/mL, at 0.74 +/- 0.43 h. At a dose of 15 g VCV, the mean C(max) was 5.26 +/- 2.82 microg/mL, at 1 +/- 0.27 h. The mean bioavailability of ACV from oral VCV was 60 +/- 12% after 5 g of VCV and 48 +/- 12% after 15 g VCV, and did not differ significantly between dose rates (P > 0.05). Superposition suggested that a loading dose of 27 mg/kg VCV every 8 h for 2 days, followed by a maintenance dose of 18 mg/kg every 12 h, will maintain effective serum ACV concentrations.

The Treatment of Herpes Simplex Infections&lt;subtitle&gt;An Evidence-Based Review&lt;/subtitle&gt;

Genital and labial herpes simplex virus infections are frequently encountered by primary care physicians in the United States. Whereas the diagnosis of this condition is often straightforward, choosing an appropriate drug (eg, acyclovir, valacyclovir hydrochloride, or famciclovir) and dosing regimen can be confusing in view of (1) competing clinical approaches to therapy; (2) evolving dosing schedules based on new research; (3) approved regimens of the Food and Drug Administration that may not match recommendations of the Centers for Disease Control and Prevention or of other experts; and (4) dissimilar regimens for oral and genital infections. The physician must first choose an approach to treatment (ie, intermittent episodic therapy, intermittent suppressive therapy, or chronic suppressive therapy) based on defined clinical characteristics and patient preference. Then, an evidence-based dosing regimen must be selected. In this review, data from all sources are tabulated to provide a handy clinical reference.

Double‐Blind Study Comparing 2 Dosages of Valacyclovir Hydrochloride for the Treatment of Uncomplicated Herpes Zoster in Immunocompromised Patients 18 Years of Age and Older

A dosage of 1 g of valacyclovir 3 times per day (TID) for 7 days has already been shown to be superior to an oral dosage of 800 mg acyclovir 5 times per day for 7 days in immunocompetent individuals. The objective of this study was to assess the safety and efficacy of an oral dosage of valacyclovir, 1 g TID versus 2 g TID, for the treatment of herpes zoster in immunocompromised patients > or =18 years of age. The oral dosage schedule of 2 g of valacyclovir TID reaches acyclovir plasma levels similar to those achieved with intravenous acyclovir therapy given to immunocompromised patients (10 mg/kg every 8 h for 7 days). In this double-blind study, 87 immunocompromised patients with clinical evidence of localized herpes zoster were randomized to receive oral valacyclovir therapy for 7 days, either 1 g TID or 2 g TID, within 72 h after onset of zoster rash. Patients were seen and assessed for cutaneous healing, zoster-associated pain (ZAP), and/or zoster-associated abnormal sensations (ZAAS), up to 24 weeks. Participants in both arms of the study demonstrated similar median times to full crusting of the rash (8 days), and both dosages were safe and effective therapies for reduction of ZAP and ZAAS in the immunocompromised patient population.

Méningite herpétique chez 11 patients

Method We reviewed retrospectively the demographic, clinical, biological characteristics and outcomes of 11 patients with HSV meningitis. Results Among the 11 patients, six were infected with HIV, four had a documented history of genital herpes, and one recurrent meningitis. In all cases, the onset of symptoms was abrupt, with severe headache and fever. On admission, 9/11 patients had severe meningismus; two patients had HSV anogenital ulcerations. CSF analysis showed in every case a significant increased of leukocytes with a lymphocytic pleocytosis, a mild elevated protein level and a normal glucose level. HSV was detected in the CSF in every case by PCR: the typing performed on six patients was positive in every case for HSV-2. Intravenous acyclovir (IV ACV) was started in 10/11 cases (range: 3–10 days), switched to valaciclovir (VACV) (range: 5–7 days); one patient was treated with ACV per os for 10 days. The total resolution of symptoms occurred within 48 hours in every case. Two patients presented with recurrent HSV-2 meningitis in the next two months, with favorable outcome under IV ACV: a switch to long term VACV 500 mg/day was prescribed without any recurrence. No patient presented with recurrence after a median follow-up of 30 months. Conclusion Early recognition and treatment might improve the outcome of such infections. Adjunctive oral VACV after IV ACV treatment seems to be associated with a good clinical response in patients presenting with HSV meningitis. The duration of such treatments, including prophylactic treatments to prevent recurrent episodes must be better documented.