Famciclovir for ophthalmic zoster: a randomised aciclovir controlled study

Abstract

Aims-To compare the eYcacy and safety of famciclovir with aciclovir for the treatment of ophthalmic zoster. Methods-Randomised, double masked, aciclovir controlled, parallel group in 87 centres worldwide including 454 patients with ophthalmic zoster of trigeminal nerve (V 1 ) comprised the intent to treat population. Oral famciclovir 500 mg three times daily or oral aciclovir 800 mg five times daily for 7 days. Assessments included day 0 (screening), days 3 and 7 (during treatment), days 10, 14, 21, 28 and monthly thereafter, up to 6 months (follow up). Proportion of patients who experienced ocular manifestations, severe manifestations and non-severe manifestations; loss of visual acuity was the main outcome measure. Results-The percentage of patients who experienced one or more ocular manifestations was similar for famciclovir (142/ 245, 58.0%) and aciclovir (114/196, 58.2%) recipients, with no significant diVerence between groups (OR 0.99; 95% CI 0.68, 1.45). The percentage of patients who experienced severe and non-severe manifestations was similar between groups, with no significant diVerence. The prevalence of individual ocular manifestations was comparable between groups. There was no significant diVerence between groups for visual acuity loss. Conclusion-Famciclovir 500 mg three times daily was well tolerated and demonstrated eYcacy similar to aciclovir 800 mg five times daily. (Br J Ophthalmol 2001;85:576-581) In 50%-72% of patients with ophthalmic herpes zoster (HZO), involvement of the ocular structures leads to ocular manifestations ranging from self limited processes to chronic ocular inflammation or neuropathy which may lead to visual loss.1-3 The mechanism of ocular manifestations is thought to include active viral replication within the eye and ophthalmic trigeminal nerve, followed by vascular and neural inflammation and damage.Aciclovir treatment for HZO has been shown to be beneficial to patients and is currently the standard of care among health practitioners. [4][5][6] Oral aciclovir at doses of 600-800 mg five times daily for 10 days significantly reduced the acute signs and symptoms of the disease and the incidence of common ocular manifestations such as dendriform keratopathy, uveitis, and stromal keratitis.7 8 However, aciclovir has poor and variable bioavailability requiring high frequency dosing regimens which can lead to diYculties with compliance. Famciclovir is the oral form of penciclovir, a nucleoside analogue which shares the same antiviral spectrum as aciclovir for herpes viruses and has similar potency and selectivity. The oral bioavailability of penciclovir is 77% following administration of famciclovir, 11 significantly higher than the bioavailability of aciclovir (10%-20%).12 In addition, the intracellular half life of penciclovir triphosphate is significantly longer than that of aciclovir triphosphate in cells infected with varicella zoster virus in vitro (1-11 hours for penciclovir triphosphate compared with <1 hour for aciclovir triphosphate). 13Famciclovir is cu...

Management of herpes zoster and postherpetic neuralgia

“…In a randomized, double-blind, parallel-group, multicenter trial in 454 patients with ophthalmic zoster, treatment with famciclovir (500 mg 3 times daily) or acyclovir (800 mg 5 times daily) for 7 days resulted in similar rates of ocular manifestations (58.0% and 58.2%, respectively; odds ratio 0.99; 95% confidence interval 0.68-1.45). 16 Through 6 months of follow-up, patients treated with famciclovir and acyclovir had similar rates of severe ocular manifestations (41.2% and 39.8%, respectively) and nonsevere ocular manifestations (44.9% and 43.4%, respectively), and a comparable prevalence of individual ocular manifestations (anterior uveitis, keratic precipitates, iridocyclitis, overall keratitis, glaucoma, disciform stromal keratitis, other keratitis, paralytic ptosis, and stromal keratitis). In another multicenter, randomized, double-blind trial, 110 immunocompetent patients with HZO were treated with valacyclovir (1000 mg 3 times daily) or acyclovir (800 mg 5 times daily) for 7 days.…”

Recommendations for the Management of Herpes Zoster

“…Treatment includes the following [217,218]: (1) approved dosages of famciclovir or valacyclovir for 7-10 days, preferably started within 72 h of rash onset (with intravenous acyclovir given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences [136,[219][220][221][222]; (2) pain medications, as discussed above; (3) cool to tepid wet compresses (if tolerated); (4) antibiotic ophthalmic ointment administered twice daily (e.g., bacitracin-polymyxin), to protect the ocular surface; (5) topical steroids (e.g., 0.125%-1% prednisolone 2-6 times daily) prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis; (6) no topical antivirals, because they are ineffective; (7) mydriatic/cycloplegia as needed for iritis (e.g., 5% homatropine twice daily); and (8) ocular pressure-lowering drugs given as needed for glaucoma (e.g., latanaprost once daily and/or timolol maleate ophthalmic gel forming solution every morning). Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit [218].…”

Varicella and Herpes Zoster. Part 1: Virology, Epidemiology, Clinical Picture, Laboratory Diagnostics

“…Auch bei jungen immunkompetenten Patienten stellt der Herpes zoster ophthalmicus eine klare Indikation für eine frühzeitige systemische antivirale Therapie dar [30]. Klinisch können neben der okulären Beteiligung (Keratitis, Chorioretinitis, Skleritis, Iridozyklitis) gefürchtete Komplikationen wie Optikusneuritiden mit möglicher Optikusatrophie, eine Beteiligung der Augenmuskeln (Paresen bis hin zur Ophthalmoplegie), eine periphere Fazialisparese, begleitende kranielle Arteriitis sowie Meningitiden bzw.…”