DrugindexOnline^{2nd edition}

Pronouncation: (fam-SYE-kloe-vir)
Class: Antiherpes virus agent

Trade Names:
Famvir
- Tablets 125 mg
- Tablets 250 mg
- Tablets 500 mg

Mechanism of Action

Pharmacology

Converts to penciclovir, which inhibits viral DNA replication by interfering with viral DNA polymerase.

Pharmacokinetics

Absorption

Bioavailability is about 77%. T _max is 0.9 h. AUC _0-∞ is 2.24 to 17.9 mcg•h/mL depending on dose. C _max is 0.8 to 6.6 mcg/mL depending on dose.

Distribution

Vd is about 1.08 L/kg; less than 20% bound to plasma proteins.

Metabolism

Route is the liver; deacetylated and oxidized to form inactive penciclovir metabolites.

Elimination

Plasma Cl is about 36.6 L/h; about 75% is renally cleared. The t _½ is about 2 to 3 h.

Special Populations

Renal Function Impairment

With Ccr 40 to 59 mL/min, Cl is about 13 L/h and t _½ is about 3.4 h. With Ccr 20 to 39 mL/min, Cl is about 4.2 L/h and t _½ is about 6.2 h. With Ccr less than 20 mL/min, Cl is about 1.6 L/h and t _½ is about 13.4 h.

Hepatic Function Impairment

Penciclovir C _max decreased 44% and T _max increased 0.75 h.

Indications and Usage

Treatment of acute herpes zoster (shingles); treatment or suppression of recurrent genital herpes in immunocompetent patients; treatment of recurrent mucocutaneous herpes simplex infections in HIV-infected patients; treatment of recurrent herpes labialis (cold sores) in immunocompetent patients.

Unlabeled Uses

Management of initial episodes of herpes genitalis.

Contraindications

Hypersensitivity to famciclovir, other components of the formulation, or penciclovir cream.

Dosage and Administration

Herpes Simplex Infections
Adults Recurrent Genital Herpes

PO 1,000 mg twice daily for 1 day. Initiate therapy at first sign or symptom. Efficacy not established when treatment is started more than 6 h after onset of symptoms or lesions.

Recurrent Herpes Labialis

PO 1,500 mg as a single dose. Initiate therapy at earliest sign or symptom of a cold sore.

Suppression of Recurrent Genital Herpes

PO 250 mg twice daily for up to 1 yr.

Renal Function Impairment Recurrent Genital Herpes

PO For Ccr at least 60 mL/min, 1,000 mg every 12 h for 1 day; for Ccr 40 to 59 mL/min, 500 mg every 12 h for 1 day; for Ccr 20 to 39 mL/min, 500 mg single dose; for Ccr less than 20 mL/min, 250 mg single dose; for hemodialysis, 250 mg single dose following dialysis.

Recurrent Herpes Labialis

PO For Ccr 60 mL/min, 1,500 mg single dose; for Ccr 40 to 59 mL/min, 750 mg single dose; for Ccr 20 to 39 mL/min, 500 mg single dose; for Ccr less than 20 mL/min, 250 single dose; for hemodialysis, 250 mg single dose following dialysis.

Suppression of Recurrent Genital Herpes

PO For Ccr 40 mL/min, 250 mg every 12 h; for Ccr 20 to 39 mL/min, 125 mg every 12 h; for Ccr less than 20 mL/min, 125 mg every 24 h; for hemodialysis, 125 mg following each dialysis.

Herpes Zoster
Adults

PO 500 mg every 8 h for 7 days. Initiate treatment immediately after diagnosis but no later than 72 h after onset of rash.

Renal Function Impairment

PO For Ccr 60 mL/min or more, 500 mg every 8 h; for Ccr 40 to 59 mL/min, 500 mg every 12 h; for Ccr 20 to 39 mL/min, 500 mg every 24 h; for Ccr less than 20 mL/min, 250 mg every 24 h.

HIV-Infected Patients
Adults Recurrent Orolabial or Genital Herpes

PO 500 mg twice daily for 7 days.

Renal Function Impairment

PO for Ccr 40 mL/min, 500 mg every 12 h; for Ccr 20 to 39 mL/min, 500 mg every 24 h; for Ccr less than 20 mL/min, 250 mg every 24 h; for hemodialysis, 250 mg following each dialysis.

General Advice

• Administer prescribed dose without regard to meals. Administer with food if GI upset occurs.

Storage/Stability

Store tablets at 59° to 86°F.

Drug Interactions

Digoxin

Famciclovir may increase digoxin serum concentration.

Probenecid or other drugs significantly eliminated by active renal tubular secretion

May increase famciclovir (penciclovir) serum concentrations.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (39%); fatigue (5%); migraine, paresthesia (3%); confusion, confusional state, delirium, disorientation, dizziness, hallucinations, somnolence (postmarketing).

Dermatologic

Pruritus (4%); rash (3%); serious skin reactions (including erythema multiforme), urticaria (postmarketing).

GI

Nausea (13%); diarrhea (9%); abdominal pain (8%); flatulence, vomiting (5%).

Genitourinary

Dysmenorrhea (8%).

Hematologic-Lymphatic

Anemia, leukopenia, neutropenia, thrombocytopenia (postmarketing).

Hepatic

Jaundice (postmarketing).

Lab Tests

Elevated amylase, ALT, AST, lipase, serum creatine, and total bilirubin (postmarketing).

Precautions

Monitor For recurrent genital herpes, assess history of frequency of recurrence. Monitor for efficacy of treatment.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Dosage adjustment is recommended when Ccr is 60 mL/min or less.

Genital herpes

Sexual intercourse must be avoided when lesions are present. Use of famciclovir does not prevent transmission.

Patient Information

• Review dose and appropriate dosing schedule depending on condition being treated (eg, cold sores, recurrent genital herpes, shingles). Instruct patient to take medication exactly as prescribed and not to stop taking or change the dose unless advised by health care provider.
• Advise patient that medication can be taken without regard to meals but to take with food if stomach upset occurs.
• Remind patient using medication for recurrent episodes of genital herpes to initiate therapy at the first sign or symptom of recurrence and that medication may not be effective if started more than 6 h after onset of signs or symptoms of recurrence.
• Advise patient with genital herpes that this drug is not a cure for genital herpes and does not prevent transmission of virus. Instruct patient to avoid sexual intercourse when lesions and/or symptoms are present to avoid infecting partner.
• Advise patient to contact health care provider if medication does not seem to be controlling lesions and/or symptoms, or if intolerable adverse reactions develop.