Uses
Oral famciclovir is used for the treatment of acute, localized herpes zoster (shingles, zoster). Oral famciclovir also is used for the treatment of genital herpes infections and for the suppression of recurrent episodes of genital herpes in immunocompetent adults. The drug also is used for the treatment of recurrent mucocutaneous herpes simplex virus (HSV) infections in adults with human immunodeficiency virus (HIV) infection. In addition, oral famciclovir is used for the episodic treatment of herpes labialis (perioral herpes, cold sores, fever blisters) in immunocompetent adults.
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Genital Herpes
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Treatment of First Episodes
Although the manufacturer states that efficacy of famciclovir for the treatment of initial episodes of genital herpes simplex virus (HSV) infection has not been established, famciclovir is considered a drug of choice for the treatment of initial episodes of genital herpes. Because many patients with first episodes of genital herpes present with mild clinical symptoms but later develop severe or prolonged symptoms, the US Centers for Disease Control and Prevention (CDC) states that most patients with initial genital herpes should receive antiviral therapy. The CDC and some clinicians recommend that first episodes of genital herpes be treated with a regimen of oral acyclovir (400 mg 3 times daily or 200 mg 5 times daily for 7-10 days), oral famciclovir (250 mg 3 times daily given for 7-10 days), or oral valacyclovir (1 g twice daily given for 7-10 days).
Studies have been initiated to compare the relative efficacy of oral famciclovir and oral acyclovir for the treatment of initial episodes of genital herpes in immunocompetent adults, and preliminary results indicate that oral famciclovir (125, 250, 500, or 750 mg 3 times daily) is as effective as oral acyclovir (200 mg 5 times daily) in terms of time to complete healing of lesions, resolution of symptoms, and time to cessation of viral shedding.
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Episodic Treatment of Recurrent Episodes
Oral famciclovir is used in the treatment of recurrent episodes of genital herpes in immunocompetent adults. Antiviral therapy for recurrent genital herpes can be given episodically to ameliorate or shorten the duration of lesions or can be given continuously as suppressive therapy to reduce the frequency of recurrences. For episodic treatment of recurrent genital herpes, the CDC and some clinicians recommend oral acyclovir (400 mg 3 times daily for 5 days, 800 mg twice daily for 5 days, or 800 mg 3 times daily for 2 days), oral famciclovir (125 mg twice daily for 5 days or 1 g twice daily for 1 day), or oral valacyclovir (500 mg twice daily for 3 days or 1 g once daily for 5 days). Episodic antiviral therapy should be initiated within 1 day of lesion onset or during the prodrome that precedes some outbreaks. The manufacturer states that patients should be advised to initiate oral famciclovir at the first sign or symptom of an episode and that there are no data on the effectiveness of the drug initiated more than 6 hours after the onset of signs and symptoms of a recurrent episode.
Efficacy of oral famciclovir for the episodic treatment of recurrent genital herpes has been evaluated in randomized double-blind, placebo-controlled studies. In one study involving 329 immunocompetent adults who self-initiated treatment within 6 hours of appearance of lesions or onset of symptoms of recurrence, the median time to lesion healing of nonaborted lesions and resolution of all symptoms was 4.3 and 3.3 days, respectively, in patients who received oral famciclovir (1 g twice daily for 1 day) compared with 6.1 and 5.4 days, respectively, in those who received placebo. The proportion of patients with aborted lesions (no development beyond erythema) was larger in the famciclovir group than in the placebo group (23 versus 13%).
Combined data from 2 studies involving 626 otherwise healthy adults who self-initiated treatment within 6 hours of appearance of lesions or onset of symptoms of recurrence indicate that the median time to lesion healing and cessation of viral shedding was 4 and 1.8 days, respectively, in patients who received oral famciclovir (125 mg twice daily for 5 days) compared with 5 and 3.4 days, respectively, in those who received placebo. The median time to resolution of all symptoms was 3.2 days in those who received famciclovir versus 3.8 days in placebo-treated patients. There is no evidence that higher dosages of famciclovir (i.e., 250 or 500 mg twice daily) provide additional benefit in terms of time to lesion healing or relief of symptoms in immunocompetent adults.
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Suppressive Therapy of Recurrent Episodes
Famciclovir is used for chronic suppressive therapy of recurrent genital herpes in immunocompetent adults. The CDC states that suppressive antiviral therapy can reduce the frequency of genital herpes recurrences by 70-80% in patients who have frequent recurrences (i.e., 6 or more per year) and many patients report no symptomatic outbreaks during such therapy. For chronic suppressive therapy of recurrent genital herpes, the CDC and some clinicians recommend a regimen of oral acyclovir (400 mg twice daily), oral famciclovir (250 mg twice daily), or oral valacyclovir (500 mg or 1 g once daily). The CDC states that data suggest that therapy with famciclovir or valacyclovir is as effective as acyclovir in terms of clinical outcome, although the 500 mg once-daily valacyclovir regimen might be less effective than acyclovir or other valacyclovir regimens in patients who have very frequent recurrences (i.e., 10 or more episodes per year).
In a study of patients with frequent recurrences of genital herpes infections (6 or more per year), 39 or 29% of those receiving famciclovir suppressive therapy (250 mg twice daily) were free of recurrences at 6 or 12 months, respectively, and 10 or 6% of those receiving placebo were free of recurrences at these time points. Safety and efficacy of oral famciclovir for suppressive therapy of recurrent genital herpes infections have been established in patients receiving daily therapy for up to 1 year.
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HIV-Infected Individuals
Immunocompromised individuals may have prolonged or severe episodes of genital, perianal, or oral herpes; HSV lesions are common in those with human immunodeficiency virus (HIV) infection and may be severe, painful, and atypical.
(See Uses: Mucocutaneous Herpes Simplex Virus Infections.) The CDC states that episodic treatment or suppressive therapy with oral antiviral agents often is beneficial in HIV-infected individuals with genital herpes. While the drugs of choice for episodic treatment or suppressive therapy of genital herpes in HIV-infected individuals are the same as those in immunocompetent adults, higher dosages and/or more prolonged therapy may be necessary. For episodic treatment of recurrences of genital herpes in HIV-infected individuals, the CDC recommends a 5- to 10-day regimen of oral acyclovir (400 mg 3 times daily), oral famciclovir (500 mg twice daily), or oral valacyclovir (1 g twice daily). For daily suppressive therapy of recurrent genital herpes in HIV-infected individuals, the CDC recommends oral acyclovir (400-800 mg 2-3 times daily), oral famciclovir (500 mg twice daily), or oral valacyclovir (500 mg twice daily).
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Patient Counseling and Management of Sexual Partners
Counseling of infected individuals and their sex partners is critical to management of genital herpes. The goals of such counseling are to help patients understand and cope with the infection and to prevent sexual and perinatal transmission of the virus. Antiviral therapy offers clinical benefit to most symptomatic patients and is the mainstay of management; however, genital herpes is a recurrent, life-long viral infection. Although antiviral therapy can be used to control the symptoms and signs of genital herpes episodes, it cannot eradicate latent HSV or affect the risk, frequency, or severity of recurrences of genital herpes when antiviral therapy is discontinued.
The majority of genital herpes infections are transmitted by individuals unaware that they have the infection or by individuals who are asymptomatic when transmission occurs. Patients should be advised that famciclovir is not a cure for genital herpes, and there are no data evaluating whether famciclovir prevents transmission of HSV to others. Because genital herpes is a sexually transmitted disease, patients should be advised to avoid sexual contact with uninfected partners when lesions and/or prodromal symptoms are present. In addition, patients should be advised that sexual transmission of the virus can occur during asymptomatic periods and that suppressive antiviral therapy reduces, but does not eliminate, subclinical viral shedding.
Sex partners of individuals with genital herpes should be advised that they may be infected even if they have no symptoms. Asymptomatic partners of patients with genital herpes should be questioned regarding a history of genital lesions, educated to recognize symptoms of genital herpes, and offered type-specific serologic testing to determine whether risk for HSV acquisition exists. Antiviral therapy is not recommended for sexual partners who do not have clinical manifestations of infection, but symptomatic sex partners of individuals with genital herpes should be evaluated and treated.
The risk for neonatal HSV infection should be discussed with all genital herpes patients, including men. Pregnant women and women of childbearing age who have genital herpes should inform their providers who care for them during pregnancy as well as those who will care for their neonates.
Information to assist patients and clinicians in counseling regarding genital herpes is available at http://www.ashastd.org and http://www.ihmf.org. For further information on treatment of initial or recurrent episodes of genital herpes or suppression of recurrent infections, .
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Herpes Labialis
Famciclovir is used for the episodic treatment of herpes labialis (perioral herpes, cold sores, fever blisters) in immunocompetent adults.
Efficacy of a 1-day regimen of famciclovir was evaluated in healthy adults with a history of recurrent cold sores. Patients were randomized to famciclovir 1.5 g as a single dose, famciclovir 750 mg twice daily for 1 day, or placebo; patients self-initiated therapy within 1 hour of symptom onset. The median time to lesion healing of nonaborted lesions and resolution of symptoms (pain and tenderness) was 4.4 and 1.7 days, respectively, in patients who received the single-dose oral famciclovir regimen compared with 6.2 and 2.9 days, respectively, in those who received placebo. There was no difference between the famciclovir-treated and placebo-treated patients in aborted lesions (no development beyond the papular stage).
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Mucocutaneous Herpes Simplex Virus Infections
Oral famciclovir is used for the treatment of recurrent mucocutaneous HSV infections (HSV-1 and HSV-2) in HIV-infected adults. The CDC, National Institutes of Health (NIH), Infectious Diseases Society of America (IDSA), and other experts state that orolabial HSV infections in HIV-infected individuals may be treated with oral acyclovir, oral famciclovir, or oral valacyclovir. IV acyclovir usually is indicated for initial treatment of moderate to severe mucocutaneous HSV infections in HIV-infected individuals but may be switched to oral antiviral therapy (acyclovir, famciclovir, valacyclovir) after lesions begin to regress. If acyclovir-resistant HSV is suspected, IV foscarnet or IV cidofovir is recommended for treatment.
In a comparative study in HIV-infected patients (40% had CD4 T-cell counts below 200/mm) with recurrent mucocutaneous HSV infections (54% with anogenital lesions, 35% with orolabial lesions) who initiated therapy within 48 hours of the onset of lesions, oral famciclovir (500 mg twice daily for 7 days) was as effective as oral acyclovir (400 mg 5 times daily for 7 days) in reducing formation of new lesions and time to complete healing.
(See HIV-infected Individuals under Uses: Genital Herpes.) Famciclovir also has been recommended for chronic suppressive or maintenance therapy (secondary prophylaxis) against HSV disease in HIV-infected adults or adolescents with frequent or severe recurrences. In patients with advanced HIV infection, reactivation of HSV frequently occurs and can result in chronic, persistent mucocutaneous disease that may be severe. The Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) has established guidelines for the prevention of opportunistic infections in HIV-infected individuals that include recommendations concerning prevention of exposure to opportunistic pathogens, prevention of first disease episodes, and prevention of disease recurrence. The USPHS/IDSA does not recommend primary prophylaxis against initial episodes of HSV infection in HIV-infected adults, adolescents, or children. In addition, the USPHS/IDSA does not recommend routine chronic suppressive or maintenance therapy (secondary prophylaxis) against HSV disease in HIV-infected individuals since acute episodes of mucocutaneous disease generally can be treated successfully with acyclovir. However, these and other experts state that long-term prophylaxis against recurrence of HSV disease can be considered for HIV-infected adults, adolescents, and children who have frequent or severe recurrences. If secondary prophylaxis is indicated in HIV-infected adults or adolescents, the USPHS/IDSA, CDC, NIH, IDSA, and other experts recommend use of oral acyclovir, oral famciclovir, or oral valacyclovir. If indicated in infants and children, the USPHS/IDSA and other experts recommend use of oral acyclovir.
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Herpes Zoster (Shingles, Zoster)
Oral famciclovir is used for the treatment of acute, localized herpes zoster (shingles, zoster) in immunocompetent adults. Some clinicians suggest that the drugs of choice for the treatment of herpes zoster in immunocompetent adults are oral acyclovir, oral famciclovir, or oral valacyclovir.
Efficacy of famciclovir in the treatment of acute, localized herpes zoster has been evaluated in a randomized, double-blind, placebo-controlled trial in immunocompetent adults and in a dose-ranging, double-blind trial in immunocompetent adults who were randomized to receive oral famciclovir (250, 500, or 750 mg 3 times daily for 7 days) or oral acyclovir (800 mg every 4 hours 5 times daily for 7 days). Results of these studies indicate that famciclovir may prevent the appearance of new lesions, decrease the duration of viral shedding, decrease the duration of pain, and promote healing and crusting of lesions in immunocompetent adults with localized herpes zoster when given within 72 hours of the onset of rash, particularly if initiated within 48 hours of rash onset. Like acyclovir, famciclovir does not appear to prevent the development of postherpetic neuralgia; the drug significantly decreases the median duration of neuralgia, particularly in patients older than 50 years of age. In comparative studies, 7 days of oral therapy with famciclovir (250-750 mg 3 times daily) was comparably effective to 7 days of oral therapy with acyclovir (800 mg 5 times daily). There were no statistically significant differences in the duration of postherpetic neuralgia between famciclovir- and acyclovir-treated patients.
Oral famciclovir has been used in a limited number of patients for the treatment of ophthalmic herpes zoster or disseminated herpes zoster or for the treatment of herpes zoster in immunocompromised patients; however, the manufacturer states that efficacy of famciclovir for the treatment of these infections has not been established. The CDC and other experts state that oral famciclovir or oral valacyclovir is the treatment of choice for localized dermatomal herpes zoster in HIV-infected adults or adolescents.
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Hepatitis B Virus Infection
Famciclovir has been used for the management of chronic hepatitis B virus (HBV) infection in a limited number of patients. The drug also has been evaluated for the control of HBV recurrence in organ or bone marrow transplant recipients. While there is some evidence suggesting that famciclovir (250-500 mg 3 times daily) is effective for the management of HBV infection, further study is needed to establish safety and efficacy.
The CDC, NIH, IDSA, and other experts state that famciclovir is not recommended for the treatment of HBV infection in HIV-infected individuals since the drug is less active than lamivudine against HBV and is not active against lamivudine-resistant HBV.