Famciclovir (Famvir) is a nucleoside (guanine) analog. It is an antiviral drug used commonly to treat infections caused by herpes simplex and herpes zoster.

Famciclovir (Famvir) Uses:

• •  It is used by immunocompetent patients for the treatment of acute herpes zoster (shingles).
  • It is used for the treatment and suppression of recurrent episodes of genital herpes in immunocompetent patients.
  • Used for the treatment of herpes labialis (cold sores) in immunocompetent patients.
  • Used for the treatment of recurrent orolabial/genital (mucocutaneous) herpes simplex in HIV-infected adult patients.

• Off Label Use of Famciclovir in Adults:

  • Used for the Genital herpes simplex virus (HSV) infection (initial episode)
  • In HIV-infected patients used for Herpes simplex virus (HSV) chronic suppressive therapy.
  • HIV-infected patients used it as Herpes zoster (shingles).
  • Used for Varicella infection (chickenpox) in HIV-infected patients

Other antiviral drugs used to treat herpes infections include:

• Acyclovir (Zovirax)
• Valacyclovir (Valtrex)

Famciclovir (Famvir) Dose inFamciclovir (Famvir) Dose in Adults

Famciclovir (Famvir) Genital herpes simplex virus (HSV) infection: Oral:

Note: Initiate therapy within 72 hours of rash onset, as soon as possible after diagnosis.

• Immunocompetent patients:

  • Initial episode (off-label use):
    • 250 mg thrice a day for 7 to 10 days. Note: Extend the treatment if healing is incomplete after 10 days of therapy.
  • Recurrence:
    • 125 mg for 5 days or 500 mg as a single dose twice in a day, followed by 250 mg for 2 days twice in a day.
  • Suppressive therapy:
    • 250 mg twice daily. Note: Duration not established, but efficacy/safety has been demonstrated for 1 year.
  • Manufacturer’s labeling:
    • Dosing in the prescribing information may not reflect current clinical practice. 1,000 mg twice in a day.

• HIV-infected patients:

  • Initial or recurrent episodes:
    • 500 mg twice in a day for 5 to 10 days
  • Chronic suppressive therapy (off-label use):
    • 500 mg two times daily;
    • suppressive therapy can be continued indefinitely regardless of CD4 count in patients with severe recurrences of genital herpes or in patients who want to minimize the frequency of recurrences, or to reduce the risk of genital ulcer disease in patients with CD4 cell counts <250 cells/mm³ who are starting antiretroviral therapy.
    • However, the continuation of therapy should be reviewed annually, particularly if immune reconstitution has occurred.
  • Manufacturer’s labeling:
    • Current clinical practice may not be reflected by dosing in the prescribing information.
    • Recurrent episodes: 500 mg Two times in a day.

Famciclovir (Famvir) Dose in the treatment of Herpes labialis/ orolabial (cold sores): Oral:

Note: Within 72 hours of rash onset initiate therapy as soon as possible after diagnosis.

• Immunocompetent patients:

  • Recurrent episodes: 1,500 mg as a single dose;
  • Start therapy at the first sign or symptom such as tingling, burning, or itching (Started within 1 hour in clinical studies).

• HIV patients:

  • Treatment: 500 mg twice in a day for 5 to 10 days.
  • Manufacturer’s labeling:
    • Current clinical practice may not be reflected by dosing in the prescribing information.
    • Recurrent episodes: 500 mg twice in a day.

Famciclovir (Famvir) Dose in the treatment of Herpes zoster (shingles): Oral:

Note: Starts therapy as soon as possible after diagnosis and within 1 week of rash onset or any time before full crusting of lesions

• Immunocompetent patients:

  • For 7 days used 500 mg every 8 hours.

• HIV-infected patients with acute localized dermatomal lesions:

  • 500 mg 3 thrice in a day for 7 to 10 days; consider longer duration if lesions heal slowly (HHS [OI adult 2016])

• HIV- infected patients with extensive cutaneous lesions or visceral involvement:

  • Initial therapy with acyclovir IV may be switched to famciclovir 500 mg thrice a day to complete a 10 to 14-day course when the formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving.

Famciclovir (Famvir) Dose in the treatment of Varicella infection (chickenpox) in HIV-infected patients (uncomplicated cases) (off-label):

• Oral: 500 mg for 5 to 7 days thrice in a day.

Famciclovir (Famvir) Dose inFamciclovir (Famvir) Dose in Children

Famciclovir (Famvir) Dose in the treatment of Herpes simplex virus (HSV) genital infection:

• Immunocompetent patients:

  • Initial episode:
    • Children weighing ≥45 kg and Adolescents:
      • Oral: 250 mg for 7 to 10 days thrice in a day.
      • Note: Treatment can be extended if healing is incomplete after 10 days of therapy.
  • Recurrence: Adolescents:
    • Note: Initiate treatment within 1 day of lesion onset or during the prodrome that precedes some outbreaks.
    • One-day regimen:
      • Oral: 1,000 mg two times daily for 1 day
    • Two-day regimen:
      • Oral: 500 mg once as a single dose, followed 12 hours later by 250 mg two times in a day for a total of 2 days.
    • Five-day regimen:
      • Oral: 125 mg for 5 days twice daily.
  • Suppressive therapy:
    • Adolescents:
      • Oral: 250 mg two times a day.
      • Note: Duration not established; efficacy/safety has been demonstrated for 1 year.

• HIV-exposed/-positive patients:

  • Initial or recurrent episodes:

    • Adolescents:
      • Oral: 500 mg for 5 to 10 days twice in a day.
      • Note: If healing is incomplete after 10 days of therapy than treatment should be extended.

  • Chronic suppressive therapy:

    • Adolescents:
      • Oral: 500 mg two times a day;
      • suppressive therapy can be continued indefinitely regardless of CD4 count in patients with severe recurrences of genital herpes or in patients who want to minimize the frequency of recurrences, or to reduce the risk of genital ulcer disease in patients with CD4 cell counts <250 cells/mm³ who are starting antiretroviral therapy.
      • However, the continuation of therapy should be reviewed annually, particularly if immune reconstitution has occurred.

Famciclovir (Famvir) Dose in the treatment of Herpes labialis/orolabial (cold sores) in HIV-exposed/-positive patients:

• Adolescents:

  • Oral: 500 mg for 5 to 10 days twice in a day.

Famciclovir (Famvir) Dose in the treatment of Herpes zoster (shingles) in HIV- exposed/-positive patients:

• Adolescents: Oral:

  • Acute localized dermatomal lesion:
    • 500 mg for 7 to 10 days thrice in a day;
    • if lesions heal slowly than consider longer duration more than 7 to 10 days.
  • Extensive cutaneous lesion or visceral involvement:
    • Initial therapy with acyclovir IV may be switched to famciclovir 500 mg thrice in a day to complete a 10- to the 14-day course when the formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving.

Famciclovir (Famvir) Dose in the treatment of uncomplicated Varicella infection (chickenpox) in HIV-exposed/-positive patients:

• Adolescents:

  • Oral: 500 mg for 5 to 7 days thrice a day.

Famciclovir (Famvir) Pregnancy Risk Category: B

• • Using it during pregnancy seems to be well-tolerated, according to available data. However, when necessary, other agents may be considered.

  Famciclovir use during breastfeeding:

  • It is unknown if famciclovir can be found in breast milk.
  • According to the manufacturer breastfeeding during therapy is a decision that should be made after considering the risks to infants and the benefits to mothers.
  • If herpes lesions have been found on the breast, breastfeeding should be avoided to prevent transmission to the infant.

Famciclovir (Famvir) Dose in Kidney Disease:

• Herpes zoster:

  • CrCl ≥60 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 40 to 59 mL/minute:
    • Every 12 hours administer 500 mg.
  • CrCl 20 to 39 mL/minute:
    • Every 24 hours administer 500mg.
  • CrCl <20 mL/minute:
    • Every 24 hours administer 250mg.
  • Hemodialysis:
    • Administer 250 mg after each dialysis session.

• Treatment of recurrent genital herpes:

  • Single-day regimen:

    • CrCl ≥60 mL/minute:
      • No dosage adjustment is necessary.
    • CrCl 40 to 59 mL/minute:
      • Administer 500 mg for 1 day every 12 hours.
    • CrCl 20 to 39 mL/minute:
      • Administer 500 mg as a single dose
    • CrCl <20 mL/minute:
      • Administer 250 mg as a single dose
    • Hemodialysis:
      • Administer 250 mg as a single dose after a dialysis session.

  • Alternatively, the following recommendations have been made (Famvir Canadian product labeling 2016):

    • CrCl >20 mL/minute/1.73 m²:
      • Administer 125 mg every 12 hours
    • CrCl <20 mL/minute/1.73 m²:
      • Administer 125 mg every 24 hours
    • Hemodialysis:
      • Administer 125 mg after each dialysis session.

• Recurrent genital herpes: Suppression:

  • CrCl ≥40 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 20 to 39 mL/minute:
    • Administer 125 mg every 12 hours
  • CrCl <20 mL/minute:
    • Administer 125 mg every 24 hours
  • Hemodialysis:
    • Administer 125 mg after each dialysis session.

• Recurrent herpes labialis: Treatment (single-dose regimen):

  • CrCl ≥60 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 40 to 59 mL/minute:
    • Administer 750 mg as a single dose
  • CrCl 20 to 39 mL/minute:
    • Administer 500 mg as a single dose
  • CrCl <20 mL/minute:
    • Administer 250 mg as a single dose
  • Hemodialysis:
    • Administer 250 mg as a single dose after a dialysis session.

• Recurrent orolabial/ genital (mucocutaneous) herpes in HIV-infected patients:

  • CrCl ≥40 mL/minute:
    • No dosage adjustment is necessary.
  • CrCl 20 to 39 mL/minute:
    • Every 24 hours administer 500 mg.
  • CrCl <20 mL/minute:
    • Every 24 hours administer 250 mg.
  • Hemodialysis:
    • Administer 250 mg after each dialysis session.

Famciclovir (Famvir) Dose in Liver disease:

• Mild-to-moderate impairment:

  • No dosage adjustment is required or necessary.

• Severe impairment:

  • No dosage adjustment provided in the manufacturer’s labeling; has not been studied.
  • However, a 44% decrease in the Concentration of penciclovir (active metabolite) was noted in patients with mild-to-moderate impairment;
  • Impaired conversion of famciclovir to penciclovir may affect efficacy.

Frequencies chances with dose and duration.

Common Side Effects of Famciclovir (Famvir):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Nausea

Less Common Side Effects of Famciclovir (Famvir):

• Central Nervous System:

  • Fatigue
  • Migraine
  • Paresthesia

• Dermatologic:

  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Diarrhea
  • Flatulence
  • Vomiting

• Genitourinary:

  • Dysmenorrhea

• Hematologic & Oncologic:

  • Neutropenia
  • Leukopenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Bilirubin

Contraindications to Famciclovir (Famvir):

• Depended on available data, use during pregnancy appears to be well tolerated; however, other agents are considered when treatment is required.

Famciclovir use during breastfeeding:

• It is not known if famciclovir is available in breast milk.
• According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
• Breastfeeding should be avoided in order to avoid transmission to the infant if herpes lesions are on the breast.

Famciclovir: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Periodic CBC during long-term therapy;
• renal function

How to administer Famciclovir (Famvir)?

Oral: May be administered without regard to meals.

Mechanism of action of Famciclovir (Famvir):

Famciclovir undergoes rapid transformation to penciclovir (active compound), which is phosphorylated in HSV-1, HSV-2 and VZV cells to a monophosphate version. This is then converted to penciclovir triphosphate and competes with deoxyguanosine triphosphate to inhibit HSV-2 polymerase, therefore, herpes viral DNA synthesis/replication is selectively inhibited. Absorption:

• Food decreases maximum peak penciclovir concentration and delays time to penciclovir peak; AUC remains the same.

Protein binding:

• Penciclovir: <20%

Metabolism:

• Famciclovir is rapidly deacetylated and oxidized to penciclovir (active prodrug); in vitro data demonstrate that metabolism does not occur via CYP isoenzymes

Bioavailability:

• Penciclovir: 77% ± 8%

Half-life elimination:

• Penciclovir: 2 to 4 hours;
• Prolonged in renal impairment:
  • CrCl 40 to 59 mL/minute: ~3.4 hours
  • CrCl 20 to 39 mL/minute: ~6.2 hours,
  • CrCl <20 mL/minute: ~13.4 hours
• Intracellular penciclovir triphosphate:
  • HSV 1: 10 hours;
  • HSV 2: 20 hours;
  • VZV: 7 hours

Time to peak:

• Penciclovir: ~1 hour

Excretion:

• Urine (73% primarily as penciclovir);
• feces (27%)

International Brand Names of Famciclovir:

• Famvir
• ACT Famciclovir
• APO-Famciclovir
• NOVO-Famciclovir
• PMS-Famciclovir
• SANDOZ Famciclovir
• Bencavir
• Ezovir
• Famcicool
• Famcino
• Famcir
• Famcler
• Famcro
• Famicle
• Famtrex
• Famvir
• Fanle
• Favic
• Fenalabial
• Herfam
• Oravir
• Rivofam
• Vectavir
• Zosfam

Famciclovir Brand Names in Pakistan: