Famciclovir

Famciclovir is the oral prodrug of penciclovir, active against herpes simplex virus and varicella zoster virus. It is used for genital herpes, herpes labialis and zoster, and its long intracellular half life allows short and single-dose regimens. It has a favourable safety profile but less data in pregnancy than acyclovir and valaciclovir.

Class. Nucleoside analogue antiviral; prodrug.

Mechanism. Converted to penciclovir, which is phosphorylated by viral thymidine kinase to the triphosphate form that competitively inhibits viral DNA polymerase.

Pharmacokinetics. About 77% bioavailable as penciclovir, rapid conversion in the intestine and liver, plasma half life of penciclovir 2 to 3 hours but intracellular half life 7 to 20 hours, renal excretion.

Genital herpes.

• First episode: 250 mg orally three times daily for 5 to 7 days.
• Recurrent episode: 1 g twice daily for 1 day (or 125 mg twice daily for 5 days); in HIV infection 500 mg twice daily for 7 days.
• Suppression: 250 mg twice daily; 500 mg twice daily in HIV infection.

Herpes labialis. 1.5 g as a single dose, taken at the first symptom.

Herpes zoster. 500 mg three times daily for 7 days, started within 72 hours of the rash.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 1.5 g in a single dose; 1.5 g daily in multiple doses.

Children. Not established; not advised.

Main alternatives. Valaciclovir or acyclovir, which have more safety data in pregnancy and children.

Contraindications. Hypersensitivity to famciclovir or penciclovir.

Serious adverse effects. Neutropenia, thrombocytopenia (rare), confusion in older adults and kidney impairment, and severe skin reactions (rare).

Common adverse effects. Headache, nausea, diarrhoea and dizziness.

Interactions. Probenecid raises penciclovir levels; few other interactions.

Common prescribing errors. Not reducing the dose in kidney impairment, treating zoster after 72 hours, and using it when acyclovir would be preferred in pregnancy.

Special groups.

• Pregnancy: limited data; acyclovir or valaciclovir preferred.
• Breastfeeding: avoid; excreted in animal milk.
• Children: not advised.
• Older adults: adjust for kidney function.
• Kidney impairment: zoster: CrCl 40 to 59 mL/min 500 mg every 12 hours; 20 to 39: 500 mg every 24 hours; under 20: 250 mg every 24 hours.
• Recurrent genital herpes single-day dose: CrCl 40 to 59: 500 mg every 12 hours for 1 day; 20 to 39: 500 mg single dose; under 20: 250 mg single dose.
• Liver impairment: mild to moderate: no adjustment; severe: conversion may be reduced.

Formulations. Tablets 125 mg, 250 mg and 500 mg.

Administration. With or without food.

Baseline. Creatinine, weight, pregnancy status.

Monitoring. Creatinine in older adults and kidney impairment; response at 48 to 72 hours.

Stopping thresholds. Stop for severe skin reaction, neutropenia or neurotoxicity.

Referral and escalation. Specialist review for ophthalmic zoster, immunocompromise or failure to respond.