Famvir

Nucleoside and Nucleotide DNA Polymerase Inhibitor Antivirals

Famciclovir may be administered without regard to meals.

seizures / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

neutropenia / Delayed / 3.2-3.2
elevated hepatic enzymes / Delayed / 2.3-3.2
migraine / Early / 0.2-3.1
hyperbilirubinemia / Delayed / 1.9-1.9
hyperamylasemia / Delayed / 1.5-1.5
leukopenia / Delayed / 1.3-1.3
anemia / Delayed / 0.1-0.1
hallucinations / Early / Incidence not known
confusion / Early / Incidence not known
delirium / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
palpitations / Early / Incidence not known

headache / Early / 8.5-39.3
nausea / Early / 2.2-12.5
diarrhea / Early / 1.6-9.0
abdominal pain / Early / 0.2-7.9
dysmenorrhea / Delayed / 0.4-7.6
vomiting / Early / 0.7-5.0
fatigue / Early / 0.6-4.8
flatulence / Early / 0.2-4.8
pruritus / Rapid / 2.2-3.7
rash / Early / 0.4-3.3
paresthesias / Delayed / 0.9-2.6
drowsiness / Early / Incidence not known
dizziness / Early / Incidence not known
urticaria / Rapid / Incidence not known

Famvir

Rx

Oral antiviral agent; prodrug for penciclovir
Indicated for tx of acute herpes zoster, tx or suppression of recurrent genital herpes in immunocompetent patients, acute tx of recurrent herpes labialis in immunocompetent patients, and tx of recurrent mucocutaneous herpes simplex infection in HIV patients
Similar spectrum of activity to acyclovir but longer duration of action

500 mg PO 3 times daily for 7 days, beginning as soon as possible after diagnosis, preferably within 48 hours of rash onset. Efficacy of therapy initiated more than 72 hours after rash onset has not been studied.[30877] The treatment of acute herpes zoster (shingles) with famciclovir will significantly decrease the incidence and duration of postherpetic neuralgia.[25698]

500 mg PO 3 times daily for 7 days. Initiate as soon as possible after diagnosis, preferably within 48 hours of rash onset. Efficacy of therapy initiated more than 72 hours after rash onset has not been studied.[30877]

500 mg PO 3 times daily for 7 to 10 days for localized infection; a longer duration of therapy may be required if lesions are slow to resolve. For those with extensive cutaneous lesions or visceral involvement, use as stepdown therapy after IV acyclovir to complete a 10- to 14-day course.[34362]

500 mg PO 3 times daily for 7 to 10 days for localized infection; a longer duration of therapy may be required if lesions are slow to resolve. For those with extensive cutaneous lesions or visceral involvement, use as stepdown therapy after IV acyclovir to complete a 10- to 14-day course.[34362]

1,000 mg PO twice daily for 1 day; 500 mg PO once, then 250 mg PO twice daily for 2 days; or 125 mg PO twice daily for 5 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. Efficacy has not been established when treatment is initiated more than 6 hours after onset of symptoms or lesion formation.

1,000 mg PO twice daily for 1 day; 500 mg PO once, then 250 mg PO twice daily for 2 days; or 125 mg PO twice daily for 5 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. Efficacy has not been established when treatment is initiated more than 6 hours after onset of symptoms or lesion formation.

250 mg PO 3 times daily for 7 to 10 days or until clinical resolution.

250 mg PO 3 times daily for 7 to 10 days or until clinical resolution. 

1,500 mg PO as a single dose at the first sign or symptom of a cold sore.

1,500 mg PO as a single dose at the first sign or symptom of a cold sore.

500 mg PO twice daily for 7 to 10 days or until clinical resolution.

500 mg PO twice daily for 7 to 10 days or until clinical resolution.

500 mg PO twice daily for 5 to 10 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. Efficacy has not been established when treatment is initiated more than 48 hours after onset of symptoms or lesion formation.

500 mg PO twice daily for 5 to 10 days. Treatment should begin at the first sign or symptom, either during the prodrome or within 1 day of lesion onset. Efficacy has not been established when treatment is initiated more than 48 hours after onset of symptoms or lesion formation.

500 mg PO twice daily for 5 to 10 days at the first sign or symptom of a cold sore. Efficacy has not been established when treatment is initiated more than 48 hours after onset of symptoms or lesion formation.

500 mg PO twice daily for 5 to 10 days at the first sign or symptom of a cold sore. Efficacy has not been established when treatment is initiated more than 48 hours after onset of symptoms or lesion formation.

250 mg PO twice daily. The safety and efficacy beyond 1 year has not been established.

250 mg PO twice daily. The safety and efficacy beyond 1 year has not been established.

500 mg PO twice daily. Although safety and efficacy beyond 1 year have not been established, guidelines suggest suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually.

500 mg PO twice daily. Although safety and efficacy beyond 1 year have not been established, guidelines suggest suppressive therapy may be continued indefinitely (without regard to CD4 count). A review of the continued need should be conducted annually.

500 mg PO 3 times daily for 7 days. Initiate therapy within 48 to 72 hours of rash onset.

500 mg PO 3 times daily for 7 days. Initiate therapy within 48 to 72 hours of rash onset.

500 mg PO 3 times daily for 7 to 14 days. Initiate therapy within 48 to 72 hours of rash onset.

500 mg PO 3 times daily for 7 to 14 days. Initiate therapy within 48 to 72 hours of rash onset.

250 mg PO 3 times daily for 5 to 7 days in combination with an oral corticosteroid. Clinical practice guidelines suggest an antiviral plus oral corticosteroid within 72 hours of symptom onset to modestly increase probability of functional facial nerve recovery.

500 mg PO 3 times daily for 5 to 7 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).

500 mg PO 3 times daily for 5 to 7 days. Initiate therapy at the first sign of symptoms (i.e., within 24 hours).

500 mg PO 3 times daily for a total treatment course of 7 to 10 days.

500 mg PO 3 times daily for a total treatment course of 7 to 10 days.

250 mg PO twice daily for 7 to 10 days.

500 mg PO twice daily for 14 to 21 days.

250 mg PO once or twice daily plus topical ophthalmic steroid for at least 10 weeks.

500 mg PO 2 to 3 times daily for 7 to 10 days plus topical ophthalmic steroid, then 250 mg PO twice daily for the duration of topical ophthalmic steroid use.

250 to 500 mg PO twice daily for 7 to 10 days plus topical ophthalmic steroid, then 250 mg PO twice daily for the duration of topical ophthalmic steroid use.

†Indicates off-label use

No dosage adjustment is recommended for patients with well-compensated hepatic impairment. The pharmacokinetics of penciclovir (the active moiety of famciclovir) have not been evaluated in patients with severe uncompensated hepatic impairment.

Treatment of herpes zoster:
CrCl 60 mL/minute or more: no dosage adjustment needed.
CrCl 40 to 59 mL/minute: 500 mg PO every 12 hours.
CrCl 20 to 39 mL/minute: 500 mg PO every 24 hours.
CrCl less than 20 mL/minute: 250 mg PO every 24 hours.
Acute treatment of recurrent herpes genitalis in immunocompetent patients:
CrCl 60 mL/minute or more: no dosage adjustment needed.
CrCl 40 to 59 mL/minute: 500 mg PO every 12 hours for 1 day.
CrCl 20 to 39 mL/minute: 500 mg PO single dose.
CrCl less than 20 mL/minute: 250 mg PO single dose.
Acute treatment of recurrent herpes labialis in immunocompetent patients:
CrCl 60 mL/minute or more: no dosage adjustment needed.
CrCl 40 to 59 mL/minute: 750 mg PO single dose.
CrCl 20 to 39 mL/minute: 500 mg PO single dose.
CrCl less than 20 mL/minute: 250 mg PO single dose.
Herpes genitalis prophylaxis in immunocompetent patients:
CrCl 40 mL/minute or more: no dosage adjustment needed.
CrCl 20 to 39 mL/minute: 125 mg PO every 12 hours.
CrCl less than 20 mL/minute: 125 mg PO every 24 hours.
Recurrent orolabial and genital herpes simplex in HIV-infected patients:
CrCl 40 mL/minute or more: no dosage adjustment needed.
CrCl 20 to 39 mL/minute: 500 mg PO every 24 hours.
CrCl less than 20 mL/minute: 250 mg PO every 24 hours.
 
Intermittent hemodialysis
For recurrent genital herpes or herpes labialis in immunocompetent patients, give 250 mg PO as a single dose following dialysis session. For herpes genitalis prophylaxis in immunocompetent patients, give 125 mg PO after each dialysis session. For herpes zoster and recurrent herpes simplex virus infection in HIV-infected patients, give 250 mg PO after each dialysis session.

Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) If possible, discontinue famciclovir at least 24 hours before administration of the varicella-zoster virus vaccine, live. Also, do not administer famciclovir for at least 14 days after vaccination. Concurrent administration of any of the varicella-zoster virus vaccines (Zostavax, Varivax, ProQuad) with antiviral medications known to be effective against varicella zoster virus has not been evaluated. Therefore, when possible, a washout period between the use of the antiviral medication and the vaccines is recommended. Refer to the most recent Center for Disease control guidance if concurrent use is necessary.
Probenecid: (Moderate) Probenecid undergoes both renal tubular secretion and renal tubular reabsorption. Concomitant administration of probenecid with famciclovir may impair clearance of the active metabolite, penciclovir. Probenecid should be avoided during therapy with famciclovir.
Probenecid; Colchicine: (Moderate) Probenecid undergoes both renal tubular secretion and renal tubular reabsorption. Concomitant administration of probenecid with famciclovir may impair clearance of the active metabolite, penciclovir. Probenecid should be avoided during therapy with famciclovir.
Talimogene Laherparepvec: (Major) Consider the risks and benefits of treatment with talimogene laherparepvec before administering acyclovir or other antivirals to prevent or manage herpetic infection. Talimogene laherparepvec is a live, attenuated herpes simplex virus that is sensitive to acyclovir; coadministration with antiviral agents may cause a decrease in efficacy.
Varicella-Zoster Virus Vaccine, Live: (Major) If possible, discontinue famciclovir at least 24 hours before administration of the varicella-zoster virus vaccine, live. Also, do not administer famciclovir for at least 14 days after vaccination. Concurrent administration of any of the varicella-zoster virus vaccines (Zostavax, Varivax, ProQuad) with antiviral medications known to be effective against varicella zoster virus has not been evaluated. Therefore, when possible, a washout period between the use of the antiviral medication and the vaccines is recommended. Refer to the most recent Center for Disease control guidance if concurrent use is necessary.

Famciclovir/Famvir Oral Tab: 125mg, 250mg, 500mg

2,000 mg/day PO for single-day therapy or 1,500 mg/day PO for multiple-day therapy.

2,000 mg/day PO for single-day therapy or 1,500 mg/day PO for multiple-day therapy.

Safety and efficacy have not been established; however, doses up to 2,000 mg/day PO for single-day therapy or 1,500 mg/day PO for multiple-day therapy have been used off-label.

weight 45 kg or more: Safety and efficacy have not been established; however, doses up to 2,000 mg/day PO for single-day therapy or 1,000 mg/day PO for multiple-day therapy have been used off-label.
weight less than 45 kg: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Penciclovir is the active antiviral compound produced by biotransformation of famciclovir. Penciclovir is a selective substrate for HSV-1, HSV-2, and varicella-zoster virus thymidine kinase (TK). Cellular kinases convert the monophosphate form of the drug to the triphosphate. In vitro studies show that penciclovir triphosphate selectively inhibits viral DNA polymerase by competing with deoxyguanosine triphosphate. Phosphorylation of penciclovir to a monophosphate form depends on viral TK, which only occurs in virus-infected cells. Inhibition of DNA synthesis of virus-infected cells inhibits viral replication. DNA synthesis in cells not infected with the virus is unaltered.
 
Penciclovir is active against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella zoster virus (VZV). The degree of antiviral activity is dependent on several factors, including the time interval between infection and treatment. Resistance of HSV and VZV to penciclovir can result from mutations in the viral TK and DNA polymerase genes. Mutations in the viral TK may lead to the complete loss of viral TK activity, reduced levels of TK activity, or alterations in the ability of viral TK to phosphorylate thymidine. The most common type of resistance is the loss of viral TK activity (TK negative isolates).

Famciclovir is administered orally.
 
Famciclovir undergoes almost complete deacetylation and oxidation to produce penciclovir and several inactive metabolites. The conversion of 6-deoxy penciclovir to penciclovir is catalyzed by aldehyde oxidase. The cytochrome P450 enzyme system appears to play little part in the metabolism of famciclovir. Penciclovir is about equally distributed in blood and plasma and < 20% bound to plasma proteins. Excretion is mostly renal, glomerular filtration and tubular secretion, with about 73% penciclovir excreted within 24 hours following oral administration and 27% excreted in the feces. Plasma elimination half-life is 2—3 hours. Reduced renal function affects clearance and indicates a dosage reduction. The intracellular half-life of penciclovir triphosphate is approximately 7 hours in VZV-infected cells, 10 hours in HSV—1 infected cells, and 20 hours in HSV—2 infected cells.

Following oral administration little or no famciclovir is detected in the plasma or urine. Famciclovir can be administered without regard to meals since the extent of systemic availability of penciclovir remains unaltered even though there may be a delay in absorption and time to peak concentration. Bioavailability of famciclovir is about 77%, much greater than that of acyclovir. Serum concentrations of penciclovir, a metabolite, are proportional to the dose of famciclovir, with no apparent accumulation over a 7 day treatment period. The time to reach maximum concentration is about 45—60 minutes.

Available data from pharmacovigilance reports have not associated use of famciclovir during pregnancy with any increased risk for major birth defects, miscarriages, or adverse maternal or fetal outcomes. Similarly, animal reproduction studies have not identified any evidence of teratogenicity. Although there are fetal risks associated with untreated herpes simplex virus during pregnancy, famciclovir should only be used during pregnancy when the benefits to the mother outweigh risks to the fetus. To monitor maternal-fetal outcomes of pregnant women exposed to famciclovir, health care providers are encouraged to register patients in the Famvir Pregnancy Registry by calling 888-669-6682.[30877]

According to the manufacturer, famciclovir should only be used in nursing mothers if the potential benefits to the mother outweigh the potential risks to the infant. It is not known if penciclovir, a metabolite of famciclovir, is excreted into human milk and there is no published experience with famciclovir during breast-feeding; thus, other agents may be preferred. Acyclovir and valacyclovir may be potential alternatives to consider during breast-feeding. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.