Famvir®

famciclovir · oral tablet

Antiviral

Approved uses

Recurrent herpes labialis and recurrent genital herpes (treatment and chronic suppression) in immunocompetent adults, and recurrent orolabial or genital herpes in HIV-infected adults

Herpes labialis 1500 mg as a single dose. Recurrent genital herpes 1000 mg twice daily for 1 day. Chronic suppression 250 mg twice daily. HIV-infected adults 500 mg twice daily for 7 days.

OFF-LABELNot in the FDA label for this product

Herpes zoster ophthalmicus

500 mg three times daily for 7 days.

RCT · n=454 · vs acyclovir

Randomized, double-masked, acyclovir-controlled parallel-group multicenter trial across 87 centers, 454 patients with V1 ophthalmic zoster in the intent-to-treat population. One or more ocular manifestations occurred in 142 of 245 (58.0%) on famciclovir 500 mg three times daily versus 114 of 196 (58.2%) on acyclovir 800 mg five times daily, odds ratio 0.99 (95% CI 0.68 to 1.45), with no significant difference in severe or non-severe manifestations, in the prevalence of individual ocular manifestations, or in visual acuity loss. The comparator was acyclovir, not placebo, so the trial establishes similar efficacy rather than a treatment effect size. Timing is the actionable variable: a review of herpes zoster antivirals states that acyclovir, valacyclovir and famciclovir started within 72 hours of acute rash onset significantly shorten acute pain, viral shedding, rash, and acute and late-onset anterior segment complications, and that valacyclovir and famciclovir also reduce the incidence and severity of postherpetic neuralgia, but that none of these agents prevents it.

Tyring S, Engst R, Corriveau C, et al. Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study. Br J Ophthalmol. 2001;85(5):576-81 (randomized controlled trial). PMID 11316720. Timing window: Pavan-Langston D. Herpes zoster antivirals and pain management. Ophthalmology. 2008;115(2 Suppl):S13-20 (review). PMID 18243927.

Contraindications

Known hypersensitivity to the product, its components, or penciclovir cream.

Available Forms

Tablets 125 mg, 250 mg and 500 mg; the 21-tablet pack of the 500 mg strength is exactly the standard 7-day zoster course

Mechanism of Action

Oral prodrug of penciclovir. In infected cells viral thymidine kinase phosphorylates penciclovir and cellular kinases complete the conversion to penciclovir triphosphate, which competitively inhibits viral DNA polymerase against deoxyguanosine triphosphate and so selectively blocks herpes viral DNA synthesis and replication.

Warnings & Precautions

Acute renal failure: Reported in patients with underlying renal disease who received doses inappropriately high for their level of renal function; reduce the dose in renal impairment.
Treatment window: Efficacy is not established when therapy starts more than 6 hours after the onset of a recurrent genital herpes episode, or more than 48 hours after onset in HIV-infected patients.
Immunocompromised patients: Efficacy and safety are not established except for treatment of recurrent orolabial or genital herpes in HIV-infected patients.
First-episode genital herpes: Efficacy and safety are not established.
Black and African American patients: Efficacy and safety are not established for recurrent genital herpes in this population.
Suppression beyond 1 year: Efficacy and safety of suppressive therapy for recurrent genital herpes beyond 1 year are not established.
Resistance and cross-resistance: Penciclovir-resistant herpes simplex arises from viral thymidine kinase or DNA polymerase mutations, and the most commonly encountered thymidine kinase negative acyclovir-resistant mutants are also resistant to penciclovir; consider resistance in patients who fail to respond or who shed virus during therapy.
Probenecid interaction: May raise penciclovir levels through competition for active renal tubular secretion; monitor for penciclovir toxicity.
Raloxifene interaction: A potent aldehyde oxidase inhibitor in vitro that could reduce the formation of penciclovir; no clinical interaction study has been conducted.

Common Side Effects

Recurrent genital herpes: Headache 13.5% versus 5.4% on placebo, diarrhea 4.9% versus 1.2%, nausea 2.5% versus 3.6%, on 1 day of treatment (n=163).
Genital herpes suppression: Headache 39.3% versus 42.9% on placebo, diarrhea 9.0% versus 9.5%, abdominal pain 7.9% versus 7.9%, nausea 7.2% versus 9.5%, dysmenorrhea 7.6% versus 6.3% (n=458).
Herpes labialis: Headache 8.5% versus 6.7% on placebo, nausea 2.2% versus 3.9%, diarrhea 1.6% versus 0.8% (n=447).
HIV-infected patients: Headache 17%, nausea 11%, diarrhea 7%, vomiting 5%, fatigue 4%, abdominal pain 3% on 500 mg twice daily (n=150).
Laboratory abnormalities: In genital herpes suppression studies, neutropenia 3.2% versus 1.5% on placebo, ALT above twice the upper normal 3.2% versus 1.5%, AST above twice the upper normal 2.3% versus 1.2%, total bilirubin above 1.5 times the upper normal 1.9% versus 1.2%.
Periocular angioedema: Angioedema of the face, eyelid, periorbital region and pharynx; postmarketing, frequency not estimable.
Neuropsychiatric: Dizziness, somnolence, seizure, hallucinations, and confusion including delirium, disorientation and confusional state occurring predominantly in the elderly; postmarketing.
Severe cutaneous reactions: Urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and hypersensitivity vasculitis; postmarketing.
Immunologic: Anaphylactic shock and anaphylactic reaction; postmarketing.
Hepatobiliary: Abnormal liver function tests and cholestatic jaundice; postmarketing.
Hematologic: Thrombocytopenia; postmarketing.

Pregnancy & Lactation

Pregnancy: Category B. No adequate and well-controlled studies in pregnant women. No adverse embryo-fetal effects were seen in rats or rabbits at oral doses providing up to 10.8 times (rats) and 5.4 times (rabbits) human systemic exposure by AUC. Use during pregnancy only if needed.

Lactation: Not known whether famciclovir or penciclovir are excreted in human milk; after oral dosing of lactating rats, penciclovir was excreted in milk at concentrations higher than in plasma. There are no infant safety data, so do not use in nursing mothers unless the potential benefits outweigh the potential risks.

Pediatric Use

Efficacy is not established in patients under 18 years of age, and the drug is not recommended in infants.