Antiherpetic medication use and the risk of gastroschisis: findings from the National Birth Defects Prevention Study, 1997-2007.

BACKGROUND: Previous studies examining the teratogenic effects of antiherpetic medications have found no associations for birth defects overall but have not examined the risk of specific birth defects. METHODS: The National Birth Defects Prevention Study ascertains population-based cases with birth defects and live-born controls without birth defects in 10 states across the United States for the purpose of identifying potential teratogenic risk factors. Mothers of cases and controls are interviewed within 2 years of their estimated date of delivery about demographic, medical and behavioural factors before and during pregnancy. This analysis examined the possible association between use of antiherpetic medications (acyclovir, valacyclovir or famciclovir) during early pregnancy and gastroschisis, a birth defect of the abdominal wall. RESULTS: The mothers of 1.1% (n = 10) of 941 gastroschisis cases and 0.3% (n = 27) of 8339 controls reported antiherpetic medication use during the month before conception through the third month of pregnancy. The adjusted odds ratios for such use in relation to gastroschisis were 4.7 [95% confidence interval 1.7, 13.3] and 4.7 [95% CI 1.2, 19.0] among women with and without self-reported genital herpes, respectively, when compared with women without antiherpetic use or herpes. Among women reporting no antiherpetic medication use, the odds ratio for self-reported genital herpes in relation to gastroschisis was 3.0 [95% CI 1.6, 5.7]. CONCLUSIONS: Our study raises the possibility of an increased risk of gastroschisis because of either antiherpetic medication use during early pregnancy or the underlying genital herpes infection for which it was indicated.

Single-dose pharmacokinetics of famciclovir in infants and population pharmacokinetic analysis in infants and children.

A multicenter, open-label study evaluated the single-dose pharmacokinetics and safety of a pediatric oral famciclovir (prodrug of penciclovir) formulation in infants aged 1 to 12 months with suspicion or evidence of herpes simplex virus infection. Individualized single doses of famciclovir based on the infant's body weight ranged from 25 to 175 mg. Eighteen infants were enrolled (1 to <3 months old [n = 8], 3 to <6 months old [n = 5], and 6 to 12 months old [n = 5]). Seventeen infants were included in the pharmacokinetic analysis; one infant experienced immediate emesis and was excluded. Mean C(max) and AUC(0-6) values of penciclovir in infants <6 months of age were approximately 3- to 4-fold lower than those in the 6- to 12-month age group. Specifically, mean AUC(0-6) was 2.2 microg h/ml in infants aged 1 to <3 months, 3.2 microg h/ml in infants aged 3 to <6 months, and 8.8 microg h/ml in infants aged 6 to 12 months. These data suggested that the dose administered to infants <6 months was less than optimal. Eight (44.4%) infants experienced at least one adverse event with gastrointestinal events reported most commonly. An updated pharmacokinetic analysis was conducted, which incorporated the data in infants from the present study and previously published data on children 1 to 12 years of age. An eight-step dosing regimen was derived that targeted exposure in infants and children 6 months to 12 years of age to match the penciclovir AUC seen in adults after a 500-mg dose of famciclovir.

Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects.

CONTEXT: Herpes simplex and herpes zoster infections are common and often treated with antiviral drugs including acyclovir, valacyclovir, and famciclovir. Safety of these antivirals when used in the first trimester of pregnancy is insufficiently documented. OBJECTIVE: To investigate associations between exposure to acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and risk of major birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based historical cohort study of 837,795 live-born infants in Denmark from January 1, 1996, to September 30, 2008. Participants had no diagnoses of chromosomal aberrations, genetic syndromes, birth defect syndromes with known causes, or congenital viral infections. Nationwide registries were used to ascertain individual-level information on dispensed antiviral drugs, birth defect diagnoses (categorized according to a standardized classification scheme), and potential confounders. MAIN OUTCOME MEASURE: Prevalence odds ratios (PORs) of any major birth defect diagnosed within the first year of life by exposure to antiviral drugs. RESULTS: Among 1804 pregnancies exposed to acyclovir, valacyclovir, or famciclovir in the first trimester, 40 infants (2.2%) were diagnosed with a major birth defect compared with 19,920 (2.4%) among the unexposed (adjusted POR, 0.89; 95% confidence interval [CI], 0.65-1.22). For individual antivirals, a major birth defect was diagnosed in 32 of 1561 infants (2.0%) with first-trimester exposure to acyclovir (adjusted POR, 0.82; 95% CI, 0.57-1.17) and in 7 of 229 infants (3.1%) with first-trimester exposure to valacyclovir (adjusted POR, 1.21; 95% CI, 0.56-2.62). Famciclovir exposure was uncommon (n = 26), with 1 infant (3.8%) diagnosed with a birth defect. Exploratory analyses revealed no associations between antiviral drug exposure and 13 different subgroups of birth defects, but the number of exposed cases in each subgroup was small. CONCLUSION: In this large nationwide cohort, exposure to acyclovir or valacyclovir in the first trimester of pregnancy was not associated with an increased risk of major birth defects.

Pharmacokinetics and safety of famciclovir in children with herpes simplex or varicella-zoster virus infection.

Two multicenter, open-label, single-arm, two-phase studies evaluated single-dose pharmacokinetics and single- and multiple-dose safety of a pediatric oral famciclovir formulation (prodrug of penciclovir) in children aged 1 to 12 years with suspicion or evidence of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection. Pooled pharmacokinetic data were generated after single doses in 51 participants (approximately 12.5 mg/kg of body weight [BW] for children weighing < 40 kg and 500 mg for children weighing > or = 40 kg). The average systemic exposure to penciclovir was similar (6- to 12-year-olds) or slightly lower (1- to < 6-year-olds) than that in adults receiving a 500-mg dose of famciclovir (historical data). The apparent clearance of penciclovir increased with BW in a nonlinear manner, proportional to BW(0.696). An eight-step weight-based dosing regimen was developed to optimize exposure in smaller children and was used in the 7-day multiple-dose safety phases of both studies, which enrolled 100 patients with confirmed/suspected viral infections. Twenty-six of 47 (55.3%) HSV-infected patients who received famciclovir twice a day and 24 of 53 (45.3%) VZV-infected patients who received famciclovir three times a day experienced at least one adverse event. Most adverse events were gastrointestinal in nature. Exploratory analysis following 7-day famciclovir dosing regimen showed resolution of symptoms in most children with active HSV (19/21 [90.5%]) or VZV disease (49/53 [92.5%]). Famciclovir formulation (sprinkle capsules in OraSweet) was acceptable to participants/caregivers. In summary, we present a weight-adjusted dosing schedule for children that achieves systemic exposures similar to those for adults given the 500-mg dose.

Single-day, patient-initiated famciclovir therapy versus 3-day valacyclovir regimen for recurrent genital herpes: a randomized, double-blind, comparative trial.

BACKGROUND: Recurrent genital herpes is a major problem for patients worldwide. Early episodic treatment with short-course therapy is effective, often stopping progression of outbreaks. This study is the first head-to-head comparison of single-day famciclovir (1000 mg administered twice daily) versus 3-day valacyclovir (500 mg administered twice daily) for episodic therapy in immunocompetent patients. METHODS: In this multicenter, multinational, double-blind, parallel-group study, 1179 adults with a history of recurrent genital herpes were randomized 1:1 to receive either famciclovir or valacyclovir. Patients initiated treatment within 6 h after a recurrence. The primary objective was to establish noninferiority of single-day famciclovir, compared with a 3-day course of valacyclovir, in time to healing of all nonaborted lesions in a modified intent-to-treat population. RESULTS: This study established that single-day famciclovir therapy was noninferior to 3-day valacyclovir therapy in reducing time to healing of all nonaborted genital herpes lesions (median time to healing, 4.25 days vs. 4.08 days). Approximately one-third of patients in each treatment group had aborted genital herpes episodes, suggesting that both treatments have similar efficacy in preventing outbreaks or progression of lesions beyond the papule stage. There was no significant difference in time to resolution of symptoms associated with recurrence. The overall incidence of adverse events was similar (23.2% for the famciclovir group vs. 22.3% for the valacyclovir group), with headache, nausea, diarrhea, vomiting, and abdominal pain reported most often. CONCLUSIONS: Single-day famciclovir (1000 mg administered twice daily) was similar to 3-day valacyclovir (500 mg administered twice daily) in both efficacy and safety, representing a more convenient treatment for immunocompetent adults with recurrent genital herpes.

Famciclovir treatment options for patients with frequent outbreaks of recurrent genital herpes: the RELIEF trial.

BACKGROUND: Recurrent genital HSV outbreaks are common among those suffering from the disease. Antiviral medications taken as suppressive therapy can reduce the frequency of these recurrences and reduce viral shedding occurring in between recurrences. OBJECTIVES: To investigate the efficacy and safety of oral famciclovir as episodic (125 mg twice daily for 5 days) and suppressive (250 mg twice daily) treatment of recurrent genital herpes (RGH). STUDY DESIGN: This was a randomized, multicenter, 6-month, open-label study. Efficacy variables were time to first recurrence of RGH symptoms, and change in total score of the Recurrent Genital Herpes Quality of Life (RGHQoL) questionnaire. Subject satisfaction questions were summarized. RESULTS: 384 subjects were randomized. There was a highly statistically significant difference between treatments in time to first recurrence of symptoms in favor of suppressive treatment (p<0.0001). There was no significant difference between treatments in total score of the RGHQoL or in subject satisfaction with treatment. CONCLUSIONS: This study demonstrated that, compared to episodic treatment, suppressive treatment with oral famciclovir may extend the time to symptomatic outbreaks in patients with frequent recurrences of genital herpes.

Famciclovir-induced leukocytoclastic vasculitis.

OBJECTIVE: To report a case of famciclovir-induced leukocytoclastic vasculitis (LCV). CASE SUMMARY: A 67-year-old white female presented to the hospital for evaluation of large, bilateral palpable purpura; coalescing ulcers with central eschars; and small, red violaceous papules on her legs and groin. Approximately 2 months prior to this hospitalization, the woman was diagnosed with shingles of her left T1-T2 nerve distribution and was treated with famciclovir 500 mg 3 times daily, which was her first exposure to this medication. Her shingles resolved; however, on day 4 of treatment, she began to notice red spots on both of her legs that began to progressively blister and increase in size. She discontinued famciclovir at that time. The rash persisted and spread to her abdomen, groin, legs, feet, and toes. She underwent punch biopsy that revealed LCV. Workup was negative for antinuclear antibody, rheumatoid factor, hepatitis B and C virus, perinuclear-staining antineutrophil cytoplasmic antibodies, cytoplasmic-staining antineutrophil cytoplasmic antibodies, antibodies to extractable nuclear antigens, proteinase 3, and myeloperoxidase. The patient improved with daily oral steroids and local wound care. DISCUSSION: LCV has been reported only once before in the English literature as of January 2008. The most common cause of LCV is medication use, but it is a diagnosis of exclusion. It is hypothesized that drugs act as haptens, which cause an immune response. An objective causality assessment using the Naranjo probability scale suggested that famciclovir was the probable cause of LCV in this patient. CONCLUSIONS: Healthcare professionals should be aware of the possible development of famciclovir-induced LCV.

Famciclovir: a review of its use in herpes zoster and genital and orolabial herpes.

Famciclovir (Famvir) is the oral prodrug of penciclovir, an agent that has demonstrated antiviral activity against herpes simplex viruses, type 1 (HSV-1) and 2 (HSV-2) [which cause orolabial and/or genital herpes simplex], and against varicella zoster virus (VZV) [a reactivation of which leads to herpes zoster]. Famciclovir has efficacy similar to that of aciclovir (in immunocompetent or immunocompromised patients) or valaciclovir (in immunocompetent patients) in the treatment of herpes zoster, and efficacy similar to aciclovir in the treatment of first or recurrent episodes of genital herpes (in immunocompetent or immunocompromised patients). Famciclovir also has efficacy in the suppression of recurrent episodes of genital herpes, and in the treatment of orolabial herpes, in immunocompetent patients. As such, famciclovir is a well tolerated first-line option for the treatment of herpes zoster and the treatment and suppression of genital herpes, and is approved for the treatment of recurrent orolabial herpes. Convenient patient-initiated single-day (for recurrent genital herpes) and single-dose (for orolabial herpes) dosage regimens may contribute to treatment compliance, patient acceptability and subsequent treatment outcomes.

Clinic-initiated, twice-daily oral famciclovir for treatment of recurrent genital herpes: a randomized, double-blind, controlled trial.

BACKGROUND: Famciclovir, the oral prodrug of penciclovir, is effective for the treatment of recurrent genital herpes. This randomized, clinic-initiated, double-blind trial compared the therapeutic efficacy and safety of treatment with famciclovir at dosages of 125 mg, 250 mg, and 500 mg twice daily for 5 days with placebo in immunocompetent adults with a recurrent episode of genital herpes. METHODS: Efficacy and tolerability were assessed in 308 patients with lesions present for no more than 6.5 h at the time of the first dose. Two assessments per day were performed to increase the precision of the determination of study end points. RESULTS: All doses of famciclovir were significantly more effective than placebo in reducing the time to cessation of viral shedding, complete lesion healing, and loss of all lesion-associated symptoms, particularly lesion tenderness, pain, and itching. Patients receiving treatment with famciclovir were significantly less likely to experience new lesions than were patients receiving placebo. All doses of famciclovir were tolerated as well as placebo was. There was no difference in efficacy or tolerability among the different doses of famciclovir; the lowest effective dose was 125 mg twice per day. CONCLUSIONS: In immunocompetent adults with recurrent genital herpes, a 5-day course of famciclovir at a dosage of 125 mg, 250 mg, or 500 mg twice per day was significantly more effective than was placebo in reducing the duration of viral shedding and symptoms and in accelerating lesion healing. These results support the use of treatment with famciclovir at a dosage of 125 mg for 5 days as an effective, well-tolerated treatment for episodes of recurrent genital herpes.

Case reports: cutaneous small vessel vasculitis due to famciclovir therapy.

Cutaneous hypersensitivity vasculitis is often idiopathic, but may be the result of therapeutic drugs. It is important to be aware of previously unreported drugs that may be associated with this complication. We report a case of cutaneous hypersensitivity vasculitis due to famciclovir therapy. To our knowledge, this is the first report of this interaction in the medical literature in English.

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

[Clinical investigation of famciclovir in chronic hepatitis B patients irresponsive to alpha interferon treatment].

OBJECTIVES: To evaluate the efficacy and safety of famciclovir on the decreasing levels of serum HBV-DNA and ALT and HBeAg/antiHBe seroconversion in chronic hepatitis B patients irresponsive to 3 months treatment with alpha interferon. METHODS: Two hundred and nineteen patients with chronic HBV infection, defined as positive HBsAg, HBeAg and HBV DNA, were enrolled and randomly half-and- half put into famciclovir and placebo groups. The two groups received either famciclovir 500 mg tid or a placebo treatment for 24 weeks, and then were followed-up for another 24 weeks with no treatment. RESULTS: At the end of 24 weeks, the log value of HBV DNA dropped from 6.54+/-1.26 to 5.70+/-2.03 in the famciclovirt group and were elevated from 6.30+/-1.32 to 6.51+/-1.65 in the placebo group (P < 0.01). The rate of cases with persistence HBV DNA dropped 2 log of quantity in the famciclovir group and was 28.28% (28/99); it was 9.47% (9/95) in the placebo group (P < 0.01). Those with persistence negative HBV DNA was 28.28% (28/99) in the flamciclovir treated group and 14.74% (14/95) in the placebo group (P < 0.05). Those persistently being HBeAg negative were 7.69% (7/91) in the famciclovir treated group and 3.33% (3/90) in the placebo group (P > 0.05). The HBeAg/antiHBe seroconversion was 4.40% (4/91) in the famciclovir group and 2.22% (2/90) in the placebo group (P > 0.05). The percentage of cases with normal of ALT level was 15.15% in the famciclovir group and 6.35% in the placebo group (P < 0.05). CONCLUSION: Famciclovir is effective in inhibiting HBV DNA replication and in decreasing serum ALT levels. The rate of HBeAg/antiHBe seroconversion in the famciclovir treated group was similar to that of the placebo group. Famciclovir was well tolerated without severe adverse effects during our treatment.

Efficacy and safety of famciclovir for treating mucocutaneous herpes simplex infection in HIV-infected individuals. Collaborative Famciclovir HIV Study Group.

OBJECTIVE: To compare the efficacy and safety of 7 days' treatment with famciclovir 500 mg twice a day versus acyclovir 400 mg five times a day, for mucocutaneous herpes simplex virus (HSV) infection in HIV-infected individuals. DESIGN: Randomized, double-blind, parallel-group study to demonstrate equivalence for the primary efficacy parameter. SETTING: Forty-eight hospital-based or specialist public-health clinics in 12 countries. PATIENTS: Two-hundred and ninety-three HIV-positive patients with recurrent HSV infection (orolabial or genital) starting treatment within 48 h of first appearance of herpetic lesions. MAIN OUTCOME MEASURES: Proportion of patients developing new lesions during treatment (primary outcome measures); Time to complete healing of lesions, time to cessation of viral shedding, time to loss of lesion-associated symptoms, number of withdrawals due to treatment failure (secondary outcome measures). RESULTS: Equivalence was defined prospectively and famciclovir was equivalent to acyclovir in preventing new lesion formation: new lesions occurred in 16.7% and 13.3% of patients, respectively [difference, 3.4%; 95% confidence interval (CI), -4.8-11.5]. The groups were comparable in time to complete healing (median 7 days for both groups; hazard ratio, 1.01; 95% CI, 0.79-1.29; P = 0.95), cessation of viral shedding (median of 2 days [hazard ratio = 0.93; 95% C.I. 0.68, 1.27; p = 0.64]), and loss of lesion-associated symptoms (median 4 days; hazard ratio, 0.99; 95% CI, 0.75-1.30; P = 0.93). Similar numbers in each group withdrew because of treatment failure. There were no differences between groups in the incidence of adverse events. CONCLUSIONS: Famciclovir given twice a day is as effective and well tolerated as high-dose acyclovir for mucocutaneous HSV infections in HIV-infected individuals, and has the convenience of less frequent dosing.

Pretransplant famciclovir as prophylaxis for hepatitis B virus recurrence after liver transplantation.

Liver transplantation in patients with detectable hepatitis B virus (HBV) DNA is associated with a high rate of HBV recurrence and detectable HBV DNA is often considered a contraindication for liver transplantation. Famciclovir, an oral form of the purine nucleoside penciclovir, has been shown to inhibit HBV replication. This pilot study was conducted to determine whether a 6-month course of famciclovir, administered before transplantation, was effective in inhibiting HBV replication in patients with end-stage liver disease caused by HBV and detectable HBV DNA and to assess the posttransplant clinical and virologic outcome of patients becoming HBV DNA negative with famciclovir prior to transplantation. All eight patients enrolled were hepatitis B surface antigen (HBsAg) positive; their HBV DNA levels at baseline ranged from 4.3 to 25,321 pg/ml (mean 3,661 pg/ml). Six of the eight patients were also seropositive for HBeAg. An initial decline in HBV DNA titers occurred in all patients; however, only 25% (two of eight) of the patients became HBV DNA negative before transplantation and underwent liver transplantation. Seroconversion to hepatitis B surface antibody (HBsAb) (and HBeAb in HBeAg-positive patient) was demonstrated at the conclusion of famciclovir in the transplanted patients. Both patients remain HBV DNA negative at nearly 2 years of follow-up after transplantation. HBV DNA remained detectable in 63% (five of eight) of the patients. The mean HBV DNA level for patients who became HBV DNA negative was 5.1 pg/ml versus 424 pg/ml in nonresponders. Adverse effects attributable to famciclovir were not observed in any of the patients. Future studies should assess the predictors of response to famciclovir so that patients likely to achieve good virologic outcome can be targeted for such a therapy.

Once, twice, or three times daily famciclovir compared with aciclovir for the oral treatment of herpes zoster in immunocompetent adults: a randomized, multicenter, double-blind clinical trial.

BACKGROUND: Famciclovir, the well absorbed oral pro-drug of penciclovir, is effective in the treatment of herpes zoster when given three times daily. Because the intracellular half-life of penciclovir triphosphate in varicella-zoster virus (VZV)-infected cells (7h) is considerably longer than that of aciclovir triphosphate (1h), it may be possible to administer famciclovir less frequently than three times daily for herpes zoster: aciclovir is administered five times daily. METHODS: 559 immunocompetent adults presenting with herpes zoster whose skin lesions were present for less than 72 h were randomized to receive famciclovir 750 mg once daily (od), 500 mg twice daily (bid), or 250 mg three times daily (tid), or aciclovir 800 mg five times daily. All treatments were given for 7 days. Participants were evaluated until complete healing or for 4 weeks, whichever occurred first. RESULTS: There were no significant differences between the four treatment groups with respect to times to full crusting; loss of vesicles, ulcers and crusts; cessation of new lesion formation; a 50% reduction in the area of affected skin; and the loss of acute pain. CONCLUSIONS: Famciclovir 750 mg once daily, 500 mg twice daily and 250 mg daily, and aciclovir 800 mg five times daily are three times comparable in efficacy with respect to the cutaneous healing of herpes zoster. The current study was not designed to assess the effects of the treatments on postherpetic neuralgia (PHN).

Famciclovir: review of clinical efficacy and safety.

Famciclovir is the well-absorbed oral form of penciclovir, an antiviral agent with potent activity against varicella-zoster virus (VZV) and herpes simplex virus (HSV-1) and 2 (HSV-2). After oral administration, famciclovir is rapidly converted to penciclovir with a bioavailability of 77%. penciclovir is efficiently phosphorylated to the active metabolite, penciclovir-triphosphate, and has a prolonged intracellular half-life of approximately 9-10 h in VZV-infected cells, and 10 and 20 h in cells infected with HSV-1 and HSV-2, respectively. Two multicenter clinical trials have shown that famciclovir given during the acute zoster phase accelerated healing of cutaneous lesions. More importantly, in a placebo-controlled study, famciclovir reduced the duration of postherpetic neuralgia (PHN), particularly in elderly patients. Famciclovir has also been proven effective in treating recurrent genital herpes, as demonstrated by a reduction in times to cessation of viral shedding, complete healing, and loss of all symptoms. One study showed that suppressive therapy with famciclovir was effective in reducing genital herpes episodes in patients with frequent recurrences. A promising new area of investigation for famciclovir is controlling virus replication in patients with chronic hepatitis B virus (HBV) or HBV reinfections after liver transplant. Results from a double-blind, placebo-controlled, pilot study and several case reports have shown that famciclovir, alone or in combination with other agents, decreased HBV-DNA levels and was tolerated with long-term treatment. Available clinical data indicate that famciclovir is an effective agent for treating herpes and holds significant promise for the treatment of chronic HBV infection HBV reinfection after liver transplantation.

Double-blind, randomized, acyclovir-controlled, parallel-group trial comparing the safety and efficacy of famciclovir and acyclovir in patients with uncomplicated herpes zoster.

This randomized, double-blind, parallel-group study compared the efficacy and safety of famciclovir administered at 250 mg thrice daily with acyclovir 800 mg 5 times daily for the treatment of acute uncomplicated herpes zoster in immunocompetent adults. A total of 55 patients participated in this trial. Twenty seven patients (49.1%) were randomized into the famciclovir plus placebo treatment group and 28 (50.9%) into the acyclovir plus placebo group. Six of the 55 patients did not complete the study. Two of these patients were in the famciclovir plus placebo group and dropped out due to deviation from the study protocol. Four patients in the acyclovir plus placebo group did not complete the study protocol due to adverse events (n = 2), deviation from the protocol (n = 1), or loss to follow-up (n = 1). Treatment was initiated within 72 h of onset of the zoster rash and was continued for 7 days. When treatment was initiated within 72 h, famciclovir was as effective as acyclovir for healing the cutaneous lesion, as indicated by the time to full crusting, loss of acute phase pain, loss of vesicles, and loss of crusts. Famciclovir was well tolerated and had a more favorable adverse event profile compared to acyclovir. Constipation, hematuria, and glycosuria were the most commonly reported adverse events, but only constipation was considered to have a possible relationship to the treatment. In conclusion, famciclovir, administered less frequently and at lower unit doses than acyclovir, is an effective treatment for uncomplicated herpes zoster.

Fatal hepatic decompensation in a patient with hepatitis B cirrhosis following famciclovir withdrawal.

Hepatitis B virus (HBV) infection is a major cause of chronic liver disease worldwide. Famciclovir is a nucleoside analogue with potent antiviral activity that appears promising in the management of patients with HBV infection. No data exist regarding the safety of nucleoside analogue withdrawal in patients treated for HBV cirrhosis. The authors describe a 41-year-old man with compensated HBV cirrhosis who developed fatal hepatic decompensation due to a rebound in viral replication within six weeks of discontinuing famciclovir therapy. Although several mutations in the HBV DNA polymerase gene have been documented, none has been associated with famciclovir resistance or adverse clinical outcomes. Clinicians should consider the risk of inducing serious flares in hepatic inflammation as a result of abrupt nucleoside analogue withdrawal. Until further data are available regarding the safety of withdrawal of these agents, indefinite treatment may be required in patients with established cirrhosis.