Famciclovir

• Herpes Zoster (Shingles)
• Genital Herpes
• Cold Sores (Herpes Labialis)
• Herpes Simplex Virus Infections

Famciclovir is an antiviral medication that is converted to penciclovir in the body, used for the treatment of herpes zoster (shingles), genital herpes, and recurrent herpes labialis (cold sores). This oral prodrug offers convenient dosing for both acute episodes and suppressive therapy.

Mechanism of Action

Famciclovir is a prodrug with no intrinsic antiviral activity. After oral administration, it is rapidly absorbed and converted to penciclovir by deacetylation and oxidation. Penciclovir is then selectively phosphorylated by viral thymidine kinase in infected cells to penciclovir monophosphate, which is further converted by cellular kinases to the active triphosphate form. Penciclovir triphosphate competitively inhibits viral DNA polymerase and is incorporated into the growing viral DNA chain, causing chain termination. The selectivity for infected cells (which contain viral thymidine kinase) minimizes toxicity to uninfected cells. Penciclovir triphosphate has a long intracellular half-life (7-20 hours), allowing for less frequent dosing.

Available Formulations

Famciclovir is available as film-coated tablets in 125 mg, 250 mg, and 500 mg strengths. The tablets can be taken with or without food. Generic formulations are available.

Medical Uses

Famciclovir is FDA-approved for acute treatment of herpes zoster (shingles) in immunocompetent adults, treatment and suppression of recurrent genital herpes in immunocompetent adults, treatment of recurrent herpes labialis (cold sores) in immunocompetent adults, and treatment of recurrent mucocutaneous herpes simplex infections in HIV-infected patients. Early initiation of therapy (within 72 hours for shingles, at first sign of prodrome for recurrent herpes) maximizes effectiveness.

Dosing Guidelines

For herpes zoster, the dose is 500 mg every 8 hours for 7 days, starting within 72 hours of rash onset. For first episode genital herpes, 250 mg three times daily for 7-10 days is recommended. For recurrent genital herpes, 125 mg twice daily for 5 days or 1000 mg twice daily for 1 day. For suppression of genital herpes, 250 mg twice daily. For herpes labialis, a single dose of 1500 mg at the first sign of outbreak. Significant dose adjustments are required for renal impairment.

Important Safety Information

Famciclovir is generally well-tolerated. The most common adverse effects are headache, nausea, and diarrhea. Patients with compromised immune systems may have reduced responses. Acute renal failure has been reported in patients with underlying renal disease receiving inappropriately high doses. Dose adjustment is essential in renal impairment. Testicular toxicity was observed in animal studies at high doses; relevance to humans at therapeutic doses is unknown.

Drug Interactions

Probenecid and other drugs that compete for renal tubular secretion may increase penciclovir concentrations. Concurrent use with varicella or zoster vaccines may reduce vaccine efficacy; avoid administration within 24 hours before to 14 days after vaccination. Famciclovir is not significantly metabolized by or does not inhibit CYP450 enzymes, so drug interactions through this mechanism are minimal. No significant interaction with digoxin, cimetidine, or antacids has been observed.

Special Populations

There are limited data on famciclovir use during pregnancy; animal studies showed no teratogenicity. Use during pregnancy only if clearly needed. A pregnancy registry existed but is now closed. It is unknown whether penciclovir is excreted in human breast milk; caution should be exercised. Safety and efficacy have not been established in pediatric patients. Elderly patients may require dose adjustment based on renal function. Significant dose reduction is required for patients with renal impairment (CrCl less than 60 mL/min). Patients with hepatic impairment showed lower penciclovir conversion; mild to moderate impairment requires no adjustment, but limited data exist for severe impairment.