Famvir
Famiciclovir therapy (famvir) for herpes simplex and herpes zoster infections.

Tyring S.

Departments of Dermatology and Microbiology/Immunology, The University of Texas Medical Branch at Galveston, Texas, USA.

Genital herpes simplex and herpes zoster infections are common afflictions that are associated with significant morbidity and a decreased quality of life. Famciclovir (Famvir, Novartis) is an orally administered prodrug of the antiviral agent penciclovir. Its unique pharmacokinetic profile makes it an efficacious, convenient and well-tolerated alternative to the traditionally prescribed acyclovir. Famciclovir is used for the acute treatment and suppressive therapy of recurrent genital herpes as well as for herpes zoster and its debilitating comorbidities. Famiciclovir allows patients to manage or prevent symptoms, thereby significantly improving their quality of life. Its favorable safety profile makes it a good treatment choice for the elderly as well as for immunocompromised patients, including those infected with HIV.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11753535&dopt=Abstract famciclovir Famvir



Famvir
Famciclovir: new preparation. Slightly helpful in herpes zoster.

[No authors listed]

A comparative placebo-controlled trial involving 419 adults showed that a one-week course of famciclovir started within 3 days of onset of skin lesions had no effect on the acute phase of zoster, the time required for scabs to fall, the end of skin lesion progression, or pain. In this trial famciclovir failed to reduce the incidence of post-zoster pain, but it did reduce its median duration by approximately 2 months. According to a subgroup analysis (not planned for by the protocol), only patients over 50 benefited from this effect. Three other trials suggest that the approved dose regimen in France (500 mg 3 times a day) may not be optimal. The dose recommended in the United Kingdom (750 mg in one daily intake or 250 mg 3 times a day) seems to be more in line with the clinical assessment file. The three available comparative trials show no statistically significant difference between famciclovir and aciclovir in terms of efficacy or tolerability. An indirect comparison suggests that the risk-benefit ratio of famciclovir and valaciclovir are probably similar. However, the effects of famciclovir on post-zoster pain were observed in a clinical trial, while those of aciclovir were found only in meta-analyses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10342925&dopt=Abstract famciclovir Famvir



Famvir
[B domain mutations in the polymerase gene of hepatitis B virus during combination therapy with thymosin alpha1 and famciclovir in Chinese asymptomatic HBV carriers]

[Article in Chinese]

Hou J, Wang Z, Sun J.

Department of Infectious Diseases, Nanfang Hospital, Guangzhou, 510515, China.

OBJECTIVE: To identify 'B domain' mutations of polymerase gene and its relationship with drug resistance during treatment with famciclovir in Chinese chronic asymptomatic HBV carriers. METHODS: Sequential sera from 29 Chinese chronic HBeAg positive HBV carriers treated with combination therapy with thymosin alpha1 (Talpha1) plus famciclovir and also from 15 cases treated with Talpha1 alone, were studied. Nucleotide sequences encoding 'B' and 'C domain' of the HBV polymerase gene were determined by direct or cloning sequencing methods. RESULTS: Nine Talpha1 plus FCV-treated and none of the Talpha1 treated patients developed mutations in the 'B domain' of polymerase gene which could result in amino acid changes. The development of 'B domain' mutations, during treatment, was significantly associated with HBV DNA rebound in those who received Talpha1 plus FCV. CONCLUSIONS: Mutations in FCV-treated patients resulting in amino acid changes mainly cluster in the 'B domain' of polymerase gene rather than in YMDD motif. The presence of mutations is significantly associated with HBV DNA rebound during treatment.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11798819&dopt=Abstract famciclovir Famvir



Famvir
Herpes Simplex Virus in Children.

Whitley RJ.

Children's Hospital at the University of Alabama at Birmingham, 1600 7th Avenue, South, ACC 616, Birmingham, AL 35233, USA. rwhitley peds.uab.edu

Herpes simplex virus (HSV) infections are ubiquitous. Children are infected with HSV resulting in totally asymptomatic acquisition to life-threatening disease. Therapy of HSV diseases of children can be considered according to severity and time of acquisition. Neonatal herpes simplex virus infections take one of three forms--disease localized to skin, eye, or mouth (SEM), encephalitis, or multiorgan disseminated disease. Treatment consists of intravenous (IV) administration of acyclovir. Supportive care for patients with life-threatening disease is an integral component of patient management. Mucocutaneous HSV infections in the immunocompromised host can be treated with either intravenous acyclovir or one of the orally bioavailable antiviral therapies. For hospitalized patients, therapy consists of IV acyclovir at 5 mg/kg every 8 hours for 7 to 14 days. For ambulatory patients, therapy is tailored according to age. For children less than 12 years of age, oral acyclovir is administered at a dosage of 20 mg/kg every eight hours. Although no controlled studies have been performed with valaciclovir or famciclovir, the pharmacokinetics of these medications would suggest superiority over acyclovir. Dosage recommendations have not been established for young children. For postpubertal children, dosage should mirror that of adults. Valaciclovir is administered at 500 mg twice daily. Famciclovir is administered at 125 mg three times daily. Herpes simplex keratoconjunctivitis is treated with topical triflurothymidine. Two drops are applied to the infected eye five times daily until resolved. Recurrences are managed in a similar manner. Some physicians administer oral acyclovir at the doses noted above in order to prevent frequent recurrences. Genital HSV infections can be treated with acyclovir, valaciclovir, or famciclovir. Episodic treatment of recurrent episodes is usually not necessary in childhood. Importantly, all data on the use of these compounds for these conditions have been generated in adults. Physician judgment is required for the management of recurrent herpes labialis, erythema multiforme, and herpes gladitorum. No controlled studies have been performed in children, although experience with acyclovir, valaciclovir, and famciclovir have resulted in their use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11931730&dopt=Abstract famciclovir Famvir



Famvir
Absence of mutations in the YMDD motif/B region of the hepatitis B virus polymerase in famciclovir therapy failure.

Gunther S, von Breunig F, Santantonio T, Jung MC, Gaeta GB, Fischer L, Sterneck M, Will H.

Heinrich-Pette-Institut fur Experimentelle Virologie und Immunologie an der Universitat, Hamburg, Federal Republic of Germany.

BACKGROUND/AIMS: Nucleoside analogues such as lamivudine and famciclovir are potent drugs for treatment of chronic hepatitis B virus infection. Breakthrough infections during lamivudine therapy are associated with mutations in the YMDD motif and putative B region of the HBV polymerase. This study investigated whether failure of famciclovir therapy is also associated with presence or emergence of particular mutations in the HBV polymerase. METHODS: We analyzed longitudinally the sequence of the priming and polymerase domain in seven patients with primary non-response to therapy and two patients with a breakthrough during therapy. Two patients who responded to therapy served as a control. RESULTS: The YMDD motif and the B region were conserved in all isolates. V-->I changes at position 555 just downstream of the YMDD motif were observed before and during therapy in a virus subpopulation of two patients with a primary non-response. In patients with a breakthrough, 378-V-->I and 424-N-->D mutations emerged in the N terminal part of the polymerase domain during follow-up. Lamivudine rescue therapy initiated in four patients, including a patient infected with YMDD(555-V-->I) variants, efficiently reduced viremia. CONCLUSIONS: These data indicate that failure of famciclovir therapy can occur independently of mutations in the YMDD motif or B region of the HBV polymerase and provide a rationale for rescue therapy with lamivudine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10365797&dopt=Abstract famciclovir Famvir



Famvir
Treatment of recurrent hepatitis B infection in liver transplant recipients.

Terrault NA.

University of California, San Francisco, CA 64143-0538, USA. noraht itsa.ucsf.edu

1. Therapeutic decisions are guided by a patient's clinical status (severity of disease and presence of comorbidities) and previous drug-exposure history. 2. Lamivudine is safe and effective in liver transplant recipients with recurrent hepatitis B virus (HBV) infection caused by wild-type virus or failure of hepatitis B immunoglobulin therapy. Lamivudine resistance, developing in approximately 25% after 12 months of therapy, is its main limitation. 3. Famciclovir is safe in liver transplant recipients; however, virological and clinical responses are less consistent than with lamivudine. Thus, lamivudine is favored over famciclovir as first-line therapy in transplant recipients with no previous exposure to nucleoside analogues. 4. Although limited in availability, adefovir dipivoxil appears safe and effective in treating liver transplant recipients with lamivudine-resistant HBV disease. Close monitoring of renal function is recommended, with dose adjustment in patients with reduced creatinine clearances. 5. Limited data suggest that intravenous ganciclovir, tenofovir disoproxil fumarate, and interferon alfa may be useful as rescue therapies for patients with lamivudine- or famciclovir-resistant HBV disease. 6. Antiviral therapy with two or more suitable agents may minimize the chance for viral resistance; therefore, future therapeutic strategies likely will use combination therapy in the long-term management of recurrent HBV disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12362303&dopt=Abstract famciclovir Famvir