(fam SYE kloe veer)
Treatment of acute herpes zoster (shingles) in immunocompetent patients; treatment and suppression of recurrent episodes of genital herpes in immunocompetent patients; treatment of herpes labialis (cold sores) in immunocompetent patients; treatment of recurrent orolabial/genital (mucocutaneous) herpes simplex in HIV-infected patients
Hypersensitivity to famciclovir, penciclovir, or any component of the formulation
Genital herpes simplex virus (HSV) infection: Oral: Note: Initiate therapy as soon as possible after diagnosis and within 72 hours of rash onset
Immunocompetent patients:
Initial episode (off-label use): 250 mg 3 times daily for 7 to 10 days (CDC [Workowski 2015])
Recurrence:
Manufacturer 's labeling: 1,000 mg twice daily for 1 day (Note: Initiate therapy as soon as possible and within 6 hours of symptoms/lesions onset)
Alternate dosing: 125 mg twice daily for 5 days or 500 mg as a single dose, followed by 250 mg twice daily for 2 days (CDC [Workowski 2015]). Note: Canadian labeling recommends 125 mg twice daily for 5 days.
Suppressive therapy: 250 mg twice daily. Note: Duration not established, but efficacy/safety have been demonstrated for 1 year (CDC [Workowski 2015]).
HIV-infected patients:
Manufacturer 's labeling: Recurrent episodes: 500 mg twice daily for 7 days
Alternate dosing:
Initial or recurrent episodes: 500 mg twice daily for 5 to 14 days (HHS [OI adult 2015])
Chronic suppressive therapy (off-label use): 500 mg twice daily; continue indefinitely regardless of CD4 count in patients with severe recurrences of genital herpes or in patients who want to minimize frequency of recurrences (HHS [OI adult 2015])
Herpes labialis/orolabial (cold sores): Oral: Note: Initiate therapy as soon as possible after diagnosis and within 72 hours of rash onset
Immunocompetent patients:
Recurrent episodes: 1,500 mg as a single dose; initiate therapy at first sign or symptom such as tingling, burning, or itching (initiated within 1 hour in clinical studies)
HIV patients:
Manufacturer 's labeling: Recurrent episodes: 500 mg twice daily for 7 days
Alternate dosing: Treatment: 500 mg twice daily for 5 to 10 days (HHS [OI adult 2015])
Herpes zoster (shingles): Oral: Note: Initiate therapy as soon as possible after diagnosis and within 72 hours of rash onset
Immunocompetent patients: 500 mg every 8 hours for 7 days
HIV-infected patients (off-label use): 500 mg 3 times daily for 7 to 10 days; consider longer duration if lesions heal slowly (HHS [OI adult 2015])
Varicella infection (chickenpox) in HIV-infected patients (uncomplicated cases) (off-label use): Oral: 500 mg 3 times daily for 5 to 7 days (HHS [OI adult 2015])
Refer to adult dosing.
Genital herpes simplex virus (HSV) in HIV-infected patients: Adolescents (off-label population): Oral:
Initial or recurrent episodes: 500 mg twice daily for 5 to 14 days (HHS [OI adult 2015])
Chronic suppressive therapy (off-label use): 500 mg twice daily; continue indefinitely regardless of CD4 count in patients with severe recurrences of genital herpes or in patients who want to minimize frequency of recurrences (HHS [OI adult 2015])
Herpes labialis/orolabial (cold sores) in HIV-infected patients: Adolescents (off-label population): Oral: Treatment: 500 mg twice daily for 5 to 10 days (HHS [OI adult 2015])
Herpes zoster (shingles) in HIV-infected patients (off-label use): Adolescents: Oral: 500 mg 3 times daily for 7 to 10 days; consider longer duration if lesions heal slowly (HHS [OI adult 2015])
Varicella infection (chickenpox) in HIV-infected patients (uncomplicated cases) (off-label use): Adolescents: Oral: 500 mg 3 times daily for 5 to 7 days (HHS [OI adult 2015])
Herpes zoster:
CrCl ≥60 mL/minute: No dosage adjustment necessary
CrCl 40 to 59 mL/minute: Administer 500 mg every 12 hours
CrCl 20 to 39 mL/minute: Administer 500 mg every 24 hours
CrCl <20 mL/minute: Administer 250 mg every 24 hours
Hemodialysis: Administer 250 mg after each dialysis session.
Recurrent genital herpes: Treatment:
U.S. labeling (single-day regimen):
CrCl ≥60 mL/minute: No dosage adjustment necessary
CrCl 40 to 59 mL/minute: Administer 500 mg every 12 hours for 1 day
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.
Canadian labeling:
CrCl >20 mL/minute/1.73 m2: No dosage adjustment necessary
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 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 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 necessary
CrCl 20 to 39 mL/minute: Administer 500 mg every 24 hours
CrCl <20 mL/minute: Administer 250 mg every 24 hours
Hemodialysis: Administer 250 mg after each dialysis session.
Mild-to-moderate impairment: No dosage adjustment is necessary
Severe impairment: No dosage adjustment provided in manufacturer 's labeling; has not been studied. However, a 44% decrease in the Cmax of penciclovir (active metabolite) was noted in patients with mild-to-moderate impairment; impaired conversion of famciclovir to penciclovir may affect efficacy.
Oral: May be administered without regard to meals.
May be taken without regard to meals.
Store at 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Famvir: 125 mg, 250 mg, 500 mg
Generic: 125 mg, 250 mg, 500 mg
Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Monitor therapy
Varicella Virus Vaccine: Famciclovir may diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of famciclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of famciclovir for 14 days after vaccination. Avoid combination
Zoster Vaccine: Famciclovir may diminish the therapeutic effect of Zoster Vaccine. Management: When possible, discontinue antiviral agents with anti-zoster activity (i.e., acyclovir, valacyclovir, famciclovir) for at least 24 hours prior to and 14 days after receiving a live attenuated zoster vaccine. Avoid combination
Periodic CBC during long-term therapy
Frequencies vary with dose and duration.
>10%:
Central nervous system: Headache (9% to 39%)
Gastrointestinal: Nausea (2% to 13%)
1% to 10%:
Central nervous system: Fatigue (1% to 5%), paresthesia ( ≤3%), migraine (1% to 3%)
Dermatologic: Pruritus ( ≤4%), skin rash ( ≤3%)
Gastrointestinal: Diarrhea (2% to 9%), abdominal pain ( ≤8%), flatulence ( ≤5%), vomiting (1% to 5%)
Genitourinary: Dysmenorrhea ( ≤8%)
Hematologic & oncologic: Neutropenia (3%)
Hepatic: Increased serum transaminases (2% to 3%), increased serum bilirubin (2%)
<1% (Limited to important or life-threatening): Anemia, angioedema (eyelid edema, facial edema, periorbital edema, pharyngeal edema), cholestatic jaundice, confusion, delirium, disorientation, dizziness, drowsiness, erythema multiforme, hallucination, hypersensitivity angiitis, palpitations, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, urticaria
With CrCl 40 to 59 mL/minute, clearance is approximately 13 L/hour; CrCl 20 to 39 mL/minute, clearance is about approximately 4.2 L/hour; CrCl less than 20 mL/minute, clearance is approximately 1.6 L/hour.
Penciclovir Cmax decreased 44% and Tmax increased 0.75 hours in patients with hepatic impairment.
Mean penciclovir AUC was 40% higher, and penciclovir renal clearance was 22% lower in elderly volunteers.
AUC of penciclovir was approximately 9.3 mcg -h/mL and 11.1 mcg -h/mL in male and female volunteers, respectively, after a single 500 mg dose. Penciclovir renal clearance was 28.5 L/h and 21.8 L/h, respectively.
Disease-related concerns:
- Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required. Acute renal failure has been reported with use of inappropriate high doses in patients with underlying renal disease.
Dosage form specific issues:
- Lactose: Tablets contain lactose; do not use with galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption syndromes.
Other warnings/precautions:
- Appropriate use: Has not been established for use in initial episodes of genital herpes, recurrent episodes of genital herpes in Black and African-American patients, patients with ophthalmic or disseminated zoster, immunocompromised patients (except HIV-infected patients with orolabial or genital herpes).
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Adverse events have not been observed in animal reproduction studies. Based on available data, use during pregnancy appears to be well tolerated (CDC [Workowski 2015]; HHS [opportunistic; adult] 2015).
Health care providers are encouraged to enroll women exposed to famciclovir during pregnancy in the Famvir Pregnancy reporting system (888-669-6682).
Famciclovir undergoes rapid biotransformation to the active compound, penciclovir (prodrug), which is phosphorylated by viral thymidine kinase in HSV-1, HSV-2, and VZV-infected cells to a monophosphate form; 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.
Food decreases maximum peak penciclovir concentration and delays time to penciclovir peak; AUC remains the same
Vd: Penciclovir: Healthy adults: 1.08 ‚ ± 0.17 L/kg
Famciclovir is rapidly deacetylated and oxidized to penciclovir (active prodrug); in vitro data demonstrate that metabolism does not occur via CYP isoenzymes
Urine (73% primarily as penciclovir); feces (27%)
Penciclovir: ~1 hour
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
Penciclovir: <20%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache, nausea, vomiting, or diarrhea (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.