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PubMed2002

Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients.

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Acyclovir↗
PubMed1997

Antiviral efficacies of famciclovir, valaciclovir, and brivudin in disseminated herpes simplex virus type 1 infection in mice.

The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. Mice intravenously inoculated with a highly virulent clinical HSV-1 isolate were orally treated by gavage over a period of 3 days starting on day 2 post infection. The reference drug acyclovir (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p < 0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice. BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly prolonged (p < 0.05) the survival time.

2-Aminopurine↗
PubMed1997

Antiviral therapy of herpes simplex and varicella-zoster virus infections.

Antiviral treatment of herpesvirus infections is rapidly changing since the advent of new drugs with improved oral availability. The efficacy of valaciclovir, the prodrug of aciclovir, and famciclovir, the prodrug of penciclovir, in the treatment of herpes genitalis and acute herpes zoster has been well documented in large clinical trials. Both drugs are effective on zoster-associated pain. Brivudin and sorivudine which are the most active compounds against varicella-zoster virus (VZV) in cell culture have also been successful in the treatment of herpes zoster. Aciclovir is still the standard therapy of severe herpes simplex virus (HSV) and varicella virus infections. In patients treated with aciclovir, the mortality of herpes encephalitis has been reduced to about 25%. The development of resistance against aciclovir and the other nucleoside analogues has not been a problem to date in the treatment of immunocompetent individuals. However, in immunocompromised patients, aciclovir-resistant HSV strains often emerge. In such cases, intravenous foscarnet is the current treatment of choice.

2-Aminopurine↗
PubMed1997

Viral lesions of the mouth in HIV-infected patients.

Viral lesions of the mouth in patients with HIV infection are common and these diseases any be a marker for HIV and disease progression. We review the spectrum of oral viral manifestations and discuss treatment modalities. The most common Epstein-Barr virus (EBV)-induced disorder in HIV-infected patients is oral hairy leukoplakia. EBV-related oral B-cell and T-cell lymphoma in AIDS patients has been described repeatedly. Herpes virus type 1 and rarely type 2 may lead to painful and resistant oral ulcers, and systemic treatment with acyclovir, valaciclovir or famciclovir is indicated. In acyclovir-resistant cases foscarnet is the treatment of choice. In recent years it has been documented that Kaposi's sarcoma, which often affects oral mucosa, is probably induced by herpesvirus type 8. Cytomegalovirus was found in 53% of cases with herpesviridae-induced mucosal ulcers as the only ulcerogenic viral agent in AIDS patients. In severe cytomegalovirus infection treatment with ganciclovir is helpful. Viral warts induced by different HPV may occur in the mouth. Several physical treatment modalities are possible in the oral mucosa. In AIDS patients mollusca contagiosa may occur as large and atypical lesions in the face and lips and rarely in the oral cavity. Cryotherapy is a bloodless treatment in such patients.

2-Aminopurine↗
PubMed2003

In vivo antiviral efficacy of a dipeptide acyclovir prodrug, val-val-acyclovir, against HSV-1 epithelial and stromal keratitis in the rabbit eye model.

PURPOSE: A dipeptide prodrug of the antiviral nucleoside acyclovir (ACV), val-val-ACV (VVACV), was evaluated in vivo as a potential drug candidate for improving antiviral efficacy against herpetic epithelial and stromal keratitis. METHODS: The effect of 1% VVACV on epithelial keratitis induced by inoculation of HSV-1 strain McKrae (25 microL of 10(5) plaque-forming units [PFU]) in the scarified rabbit cornea and stromal keratitis induced by intrastromal injection of HSV-1 strain RE (10 microL of 10(5) PFU) was compared with that of 1% trifluorothymidine (TFT) and balanced salt solution as the vehicle control. Both eyes of 10 rabbits were used in each treatment group. Lesions were evaluated by slit lamp examinations over a 2-week period after infection. Aqueous humor samples and corneas were analyzed for drug concentrations at the end of each experiment. Cytotoxicity of VVACV in comparison with val-acyclovir (VACV), ACV, and TFT was evaluated in cellular proliferation assays. RESULTS: The dipeptide prodrug VVACV demonstrated excellent activity against HSV-1 in the rabbit epithelial and stromal keratitis models: 1% VVACV was as effective as 1% TFT. The prodrug was also less cytotoxic than TFT, which is the only effective drug currently licensed and routinely used for topical treatment of ocular herpes infections in the United States. CONCLUSIONS: The less cytotoxic and highly water-soluble prodrug VVACV, which showed excellent in vivo activity against HSV-1 in rabbit epithelial and stromal keratitis, is a promising drug candidate for treatment of ocular HSV infections.

Acyclovir↗
PubMed2004

Epidural blood patch and acute varicella.

We present the case of a 38-yr-old woman who required an epidural blood patch in the context of acute varicella (chickenpox). The unique risks in this case include the possible triggering of central nervous system complications after the introduction of viremic blood into the epidural or intrathecal space. However, the risk was believed to be acceptable because the patient was receiving antiviral coverage. She enjoyed complete relief of her headache but experienced transient back and leg pain. Leptomeningeal irritation caused by acute varicella infection may put patients at increased risk for pain after epidural blood patch.

Acute Disease↗
PubMed2004

New strategies for the diagnosis, treatment, and prevention of herpes simplex in contact sports.

Sports participation may result in myriad cutaneous manifestations, from mundane findings to life-threatening illnesses. Skin infections are among the most common dermatologic ailments in athletes; herpes simplex is clearly among the most serious for the individual athlete, and ultimately the team. Herpes simplex infection most often involves athletes with extensive skin to skin contact. For a variety of reasons, wrestlers and rugby players seem particularly prone. The keys to thwarting epidemics and reducing an athlete's disqualification period include early diagnosis, rapid institution of therapy, and routine systematic preventative measures. This clinical review examines the classification, epidemiology, diagnosis, treatment, and prevention of herpes simplex virus infection as it relates to contact sports. Attention to evidence-based medicine is paid to treatment and prevention techniques. Practical implications for all concerned parties, including athletes, parents, coaches, trainers, and physicians, are discussed.

Acyclovir↗
PubMed2003

The epidemiology and clinical analysis of several outbreaks of herpes gladiatorum.

UNLABELLED: PURPOSE The purpose of this analysis was to determine whether present National Federation of State High School Associations (NFHS) guidelines adequately prevent and control outbreaks of primary herpes gladiatorum (HG) in high-school wrestlers. METHODS: Using telephone interviews, direct physical examinations, and review of medical charts, data were collected on HG outbreaks among participating teams in the 1999 Minnesota State High School League (MSHSL) wrestling season and on HG outbreaks for 3 yr at a 28-d summer wrestling camp. RESULTS: The outbreak during the 1999 MSHSL wrestling season involved 61 wrestlers and three coaches on 19 teams over 42 d, with a 32.7% probability of transmission to sparring partners. Typical length of time from exposure to outbreak varied from 4 to 11 d with an average of 6.80 +/- 1.70 d. Analysis of data from three outbreaks at a 28-d wrestling camp showed that most outbreaks (96%) occurred on the ventral surface of the body, with 71.9% on the head, face, and neck, areas in direct contact when wrestlers are engaged in the lock-up position. Analysis of data from the 2001 camp outbreak showed that the locations of the lesions reflected the handedness of the wrestler. CONCLUSION: The NFHS guidelines are inadequate to prevent and control outbreaks of HG. The focus of preventive efforts needs to change from mat cleanliness to more rapid detection of outbreaks by requiring culture results and appropriate therapy for all suspected bacterial and herpes lesions before allowing return to contact. To minimize and control spread of HG, treatment and isolation should be implemented based not only on vesicle formation but also on systemic signs and symptoms.

2-Aminopurine↗
PubMed2004

Valtrex therapy for Epstein-Barr virus reactivation and upper respiratory symptoms in elite runners.

PURPOSE: The aim of the study was to examine the effectiveness of prophylactic administration of the antiviral agent Valtrex for control of Epstein-Barr virus (EBV) reactivation and upper respiratory symptoms in elite distance runners. METHODS: Twenty elite male distance runners were randomized into a 4-month double-blind, placebo-controlled cross-over trial. Saliva samples were collected weekly and mucosal immune status assessed by measurement of secretory IgA (SIgA) using an enzyme-linked immunosorbent assay (ELISA). EBV reactivation was monitored at the same time by detection of EBV in saliva using a quantitative real-time polymerase chain reaction. The initial EBV status of the runners was determined by detecting EBV antibodies in serum using an ELISA. Upper respiratory symptoms were recorded using self-reporting illness logs. RESULTS: There was no evidence of any marked change in maximal oxygen uptake (P = 0.86), training volume (P = 0.30), or mucosal immunity (P = 0.21) over the study period. Valtrex treatment resulted in an 82% reduction in the detectable EBV load in saliva for EBV seropositive runners compared with the placebo treatment (P = 0.04). The incidence of upper respiratory symptoms was not reduced by Valtrex treatment. CONCLUSIONS: The prophylactic administration of Valtrex reduced EBV reactivation but was not an effective intervention strategy for limiting upper respiratory symptoms in this cohort of elite distance runners. The upper respiratory symptoms in the distance runners could not be directly attributed to infection and may be of a noninfectious inflammatory nature.

Acyclovir↗
PubMed2002

Valaciclovir versus aciclovir for herpes simplex virus infection in HIV-infected individuals: two randomized trials.

Our objective was to evaluate valaciclovir for anogenital herpes in HIV-infected individuals using 2 controlled trials conducted before highly active antiretroviral therapy (HAART) was used. In Study 1, 1062 patients (CD4+ > or = 100 cells/mm(3)) received suppressive valaciclovir or aciclovir for one year and were assessed monthly. In Study 2, 467 patients were treated episodically for > or =5 days with valaciclovir or aciclovir and evaluated daily. Valaciclovir was as effective as aciclovir for suppression and episodic treatment of herpes. Hazard ratios [95% confidence interval (CI)] for time to recurrence for valaciclovir 500 mg twice daily and 1000 mg once daily vs aciclovir were 0.73[0.50, 1.06], P=0.10, and 1.31[0.94, 1.82], P=0.11. Valaciclovir 500 mg twice daily was superior to 1000 mg once daily, P=0.001. Valaciclovir 1000 mg twice daily was comparable to aciclovir on herpes episode duration (hazard ratio 0.92[0.75, 1.14]). Adverse events were similar among treatments. In conclusion, valaciclovir is a safe, effective, convenient alternative to aciclovir for HSV infection in HIV-infected individuals.

AIDS-Related Opportunistic Infections↗
PubMed2004

Antiviral treatment of genital herpes.

A review of the randomized, controlled trials in the literature on the treatment of genital herpes infection with aciclovir, famciclovir and valaciclovir. Common clinical questions encountered by physicians, such as the effect of antivirals on symptoms, healing, aborting attacks and subsequent recurrences, are addressed. There is very little comparative data between the three licensed drugs but the little data that there is shows no difference in efficacy, tolerability and toxicity between aciclovir, valaciclovir or famciclovir when taken orally. Choice of therapy would then depend on convenience of dosing and cost.

2-Aminopurine↗
PubMed2004

Treatment modalities and medication recommended by health care professionals for treating recurrent herpes labialis.

BACKGROUND: The authors conducted a survey to determine how health care professionals respond to patients' inquiries about cold sores, also known as recurrent herpes labialis, and their choices of treatment modalities and medications. METHODS: The authors mailed a one-page, pretested survey to a random sample of dentists, pharmacists and family physicians in Alberta, Canada. After receiving ethics approval from the University of Alberta, Edmonton, the authors mailed 998 surveys. The response rate was 51 percent. RESULTS: Topical antiviral medication was the most common treatment recommended (63 percent). Over-the-counter medication was the first choice for pharmacists (83 percent) as compared with dentists (15 percent) and physicians (16 percent). Emotional stress (60 percent) was reported by patients to be the most common trigger, and pain or discomfort (81 percent) was their primary concern. Acyclovir ointment was the most common antiviral drug recommended or prescribed by health care professionals (60 percent), and cost was the major reason they gave for not recommending or prescribing antiviral drugs (73 percent). CONCLUSIONS: The authors found variation in treatment modalities and recommendations by each health profession, despite the fact that patients reported similar triggers and concerns. This may be due to individual patient need and the health care professional's lack of knowledge. PRACTICE IMPLICATIONS: Survey results may serve as a reference for health care professionals to use to determine how their choices of medications and treatment modalities compare with those of other practitioners. Professionals should know the benefits and limitations of all therapies, discuss them with the patients and select a treatment.

2-Aminopurine↗
PubMed2006

Prevention of cytomegalovirus infection by valaciclovir after allogeneic bone marrow transplantation from an unrelated donor.

In this prospective single-center study, we evaluated the efficacy and safety of valaciclovir (VACV) in the prevention of cytomegalovirus (CMV) infection after allogeneic bone marrow transplantation (BMT). The study population consisted of 12 patients who underwent allogeneic BMT from an unrelated donor. Patients received acyclovir (ACV) intravenously until they became able to take VACV orally. VACV was administered at a daily dose of 3000 mg and continued until day 100. CMV infection was monitored by CMV antigenemia assay and real-time polymerase chain reaction analysis of plasma. Thirty-five patients who did not receive any form of CMV chemoprophylaxis served as control subjects. CMV infection was detected in 4 (33.3%) of the 12 patients and in 24 (68.6%) of the 35 control subjects (P < .05). The onset of CMV infection was significantly delayed in the VACV group (median, day 43) compared with the control group (median, day 28.5; P < .01). Gastrointestinal symptoms as an adverse event due to VACV administration were observed in 2 patients. The plasma levels of ACV after VACV administration were measured in 8 patients and were similar to those in the healthy subjects. In conclusion, VACV shows normal absorption, even in the early posttransplantation period, and may prevent or delay CMV infection effectively and safely in allogeneic BMT recipients.

Acyclovir↗
PubMed1995

Pharmacokinetics of new antiherpetic agents.

Valaciclovir and famciclovir, two new prodrugs (for aciclovir and penciclovir, respectively) have similar pharmacokinetics in many regards. Both have good but incomplete bioavailability, with the conversion to the active forms taking place in the liver, but by different cytosolic enzymes. Absorption and conversion are consistent in relevant patient groups, including those with liver disease. The pharmacokinetics of both active molecules are also similar in being mainly renally eliminated, a significant component of which is tubular secretion, and elimination half-lives from plasma of approximately 2.2 to 2.5 hours. Dosage adjustment is required in the presence of renal impairment. No clinically important drug interactions have been identified with either drug. The choice between the two agents is likely to depend on clinical factors such as tolerability, safety, efficacy, compliance and possibly cost, rather than on their pharmacokinetics.

2-Aminopurine↗
PubMed2004

Evaluation of pharmacokinetic interactions after oral administration of mycophenolate mofetil and valaciclovir or aciclovir to healthy subjects.

OBJECTIVE: To investigate a potential pharmacokinetic interaction between mycophenolate mofetil (MMF) and aciclovir or valaciclovir. STUDY DESIGN AND PARTICIPANTS: Fifteen healthy subjects were enrolled in a prospective, randomised, open-label, single-dose, cross-over study conducted at a single centre. Subjects received each of the following five oral treatments: (i) aciclovir 800 mg alone; (ii) valaciclovir 2 g alone; (iii) MMF 1 g alone; (iv) valaciclovir 2 g + MMF 1 g; and (v) aciclovir 800 mg + MMF 1 g. The following pharmacokinetic parameters were estimated for aciclovir, mycophenolic acid (MPA) and its inactive glucuronide metabolite (MPAG) from the plasma concentration-time data using noncompartmental methods: area under the concentration-time curve from zero to infinity (AUC infinity), terminal elimination half-life (t1/2z), peak concentration (Cmax) and time to Cmax (tmax). The renal clearance (CLR) of aciclovir was also calculated. These parameters were compared when aciclovir or valaciclovir were coadministered with MMF relative to aciclovir, valaciclovir or MMF given alone. RESULTS AND DISCUSSION: Aciclovir Cmax, tmax and AUC infinity were significantly increased by 40%, 0.38 hour and 31%, respectively, following coadministration of aciclovir and MMF, whereas aciclovir t1/2z was significantly decreased by 11%. Following coadministration of valaciclovir and MMF, aciclovir pharmacokinetic parameters were not significantly modified except for tmax (about 0.5 hour shorter with MMF). MPA and MPAG pharmacokinetic parameters were not significantly modified following coadministration of MMF with valaciclovir or aciclovir except for MPAG AUC infinity, which was decreased by 12% with valaciclovir. Our results are similar to those reported in the literature, except for MPAG AUC. In urine, following coadministration of aciclovir and MMF, aciclovir CLR was significantly decreased by 19%. Competition between MPAG and aciclovir for renal tubular secretion could partly explain this phenomenon. Following coadministration of valaciclovir and MMF, aciclovir CLR was not significantly modified. CONCLUSION: In healthy subjects, interactions are observed after coadministration of MMF and aciclovir, but the extent of the interactions is unlikely to be of clinical significance. These interactions should be investigated in patients with abnormal renal function.

Acyclovir↗
PubMed1996

Valaciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in herpesvirus infections.

Valaciclovir, the L-valyl ester of aciclovir (acyclovir), is an oral prodrug that undergoes rapid and extensive first-pass metabolism to yield aciclovir and the essential amino acid L-valine. Aciclovir, the active antiviral component of valaciclovir, shows good in vitro activity against the herpesviruses herpes simplex virus (HSV)-1, HSV-2 and varicella zoster virus. The bioavailability of aciclovir from oral valaciclovir is considerably greater than that achieved after oral aciclovir administration. Thus, valaciclovir delivers therapeutic aciclovir concentrations when administered in a less frequent oral dosage regimen than is required for aciclovir. Valaciclovir is an effective treatment for herpes zoster in immunocompetent adults. In a large comparative study that included patients > or = 50 years of age, valaciclovir (1000mg 3 times daily for 7 or 14 days) and oral aciclovir (800mg 5 times daily) were equally effective in achieving resolution of cutaneous zoster lesions. Importantly, valaciclovir was significantly more effective than aciclovir in reducing the duration of zoster-associated pain. Preliminary results of several studies indicate that valaciclovir (500 to 1000mg twice daily for 5 to 10 days) is as effective as aciclovir (200mg 5 times a day for 5 to 10 days) in the treatment of genital herpes. In patients with first or recurrent episodes of genital herpes, valaciclovir reduced the duration of viral shedding, hastened lesion healing and decreased lesion-associated pain. Valaciclovir was also effective in suppressing recurrent episodes of genital herpes and significantly prolonged the time to a recurrent episode of infection compared with placebo. Valaciclovir is a well tolerated drug; in herpes zoster and HSV studies its tolerability profile was similar to that of aciclovir or placebo. Valaciclovir represents and advance in antiherpes drug therapy and is a useful treatment option for patients with herpes zoster or genital herpes. It is at least as effective as aciclovir and is administered in a more convenient oral dosage regimen. Thus, valaciclovir may ultimately succeed aciclovir as a first-line treatment for genital herpes or herpes zoster.

Acyclovir↗