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Famciclovir

Pronunciation

Pronunciation

(fam SYE kloe veer)

Dosage Forms

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

Brand Names: U.S.

  • Famvir

Pharmacologic Category

  • Antiviral Agent

Pharmacology

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.

Absorption

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

Distribution

Vd: Penciclovir: Healthy adults: 1.08 ± 0.17 L/kg

Metabolism

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

Excretion

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

Time to Peak

Penciclovir: ~1 hour

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

Protein Binding

Penciclovir: <20%

Special Populations: Renal Function Impairment

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.

Special Populations: Hepatic Function Impairment

Penciclovir Cmax decreased 44% and Tmax increased 0.75 hours in patients with hepatic impairment.

Special Populations: Elderly

Mean penciclovir AUC was 40% higher, and penciclovir renal clearance was 22% lower in elderly volunteers.

Special Populations: Children

There are no pharmacokinetic data in children to support a famciclovir dose that provides penciclovir exposure comparable with the penciclovir systemic exposures in adults after a single dose of 1,500 mg.

Special Populations: Gender

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.

Use: Labeled Indications

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

Contraindications

Hypersensitivity to famciclovir, penciclovir, or any component of the formulation

Dosage

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: Adults:

Initial episode: 250 mg 3 times/day for 7 to 10 days (CDC, 2010)

Recurrence: 1,000 mg twice daily for 1 day (Note: Initiate therapy as soon as possible and within 6 hours of symptoms/lesions onset)

Alternatively, the following regimens are also recommended: 125 mg twice daily for 5 days or 500 mg as a single dose, followed by 250 mg twice daily for 2 days (CDC, 2010). Note: Canadian labeling recommends 125 mg twice daily for 5 days.

Suppressive therapy: 250 mg twice daily for up to 1 year; Note: Duration not established, but efficacy/safety have been demonstrated for 1 year (CDC, 2010)

HIV-infected patients:

Manufacturer’s labeling: Recurrent episodes: Adults: 500 mg twice daily for 7 days

Alternate dosing: Adolescents (off-label population) and Adults:

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: Adults:

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: Adults: 500 mg twice daily for 7 days

Alternate dosing: Adolescents (off-label population) and Adults: Treatment: 500 mg twice daily for 5 to 10 days (HHS [OI adult 2015])

Herpes zoster (shingles): Oral:

Immunocompetent patients: Adults: 500 mg every 8 hours for 7 days. Note: Initiate therapy as soon as possible after diagnosis and within 72 hours of rash onset

HIV-infected patients (off-label use): Adolescents and Adults: 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: Adolescents and Adults: 500 mg 3 times daily for 5 to 7 days (HHS [OI adult 2015])

Dosing adjustment in renal impairment:

Herpes zoster:

CrCl ≥60 mL/minute: No dosage adjustment necessary

CrCl 40-59 mL/minute: Administer 500 mg every 12 hours

CrCl 20-39 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 40-59 mL/minute: Administer 500 mg every 12 hours for 1 day

CrCl 20-39 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 20-39 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 40-59 mL/minute: Administer 750 mg as a single dose

CrCl 20-39 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 20-39 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.

Dosage adjustment in hepatic impairment:

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.

Administration

May be administered without regard to meals.

Dietary Considerations

May be taken without regard to meals.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

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

Adverse Reactions

Note: 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%), migraine (1% to 3%)

Dermatologic: Pruritus (≤4%), rash (≤3%)

Endocrine & metabolic: Dysmenorrhea (≤8%)

Gastrointestinal: Diarrhea (2% to 9%), abdominal pain (≤8%), vomiting (1% to 5%), flatulence (≤5%)

Hematologic: Neutropenia (3%)

Hepatic: Transaminases increased (2% to 3%), bilirubin increased (2%)

Neuromuscular & skeletal: Paresthesia (≤3%)

<1% (Limited to important or life-threatening): Anemia, angioedema (eyelid, face, periorbital, pharyngeal edema), cholestatic jaundice, confusion, delirium, disorientation, dizziness, erythema multiforme, hallucinations, leukocytoclastic vasculitis, palpitations, somnolence, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, urticaria

Warnings/Precautions

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).

Monitoring Parameters

Periodic CBC during long-term therapy

Pregnancy Risk Factor

B

Pregnancy Considerations

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).

Patient Education

• 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, 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.

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