Oral famciclovir, topical penciclovir, and intravenous penciclovir are approved for HSV and VZV infections in various countries. Oral famciclovir (250 mg three times a day for 7—10 days) is as effective as acyclovir in treating first-episode genital herpes. In patients with recurrent genital HSV, patient-initiated famciclovir treatment (125 or 250 mg twice a day for 5 days) reduces healing time and symptoms by ~1 day. Famciclovir (250 mg twice a day for up to 1 year) effectively suppresses recurrent genital HSV, but single daily doses are less effective. Higher doses (500 mg twice a day) reduce HSV recurrences in HIV-infected persons. Intravenous penciclovir (5 mg/kg every 8 or 12 hours for 7 days) is comparable with intravenous acyclovir for mucocutaneous HSV infections in immunocompromised hosts. In immunocompetent persons with recurrent orolabial HSV, topical 1% penciclovir cream (applied every 2 hours while awake for 4 days) shortens healing time and symptoms by ~1 day.
In immunocompetent adults with VZV of <3 days duration, famciclovir (500 mg three times a day for 10 days) is at least as effective as acyclovir in reducing healing time and zoster-associated pain, particularly in older individuals. Famciclovir is comparable with valacyclovir in treating zoster and reducing associated pain in older adults. Famciclovir (500 mg three times a day for 7—10 days) also is comparable with high-dose oral acyclovir in treating zoster in immunocompromised patients and in those with ophthalmic zoster.
Famciclovir causes dose-related reductions in HBVDNA and transaminase levels in patients with chronic HBV hepatitis but is less effective than lamivudine. Famciclovir is also ineffective in treating lamivudine-resistant HBV infections owing to emergence of multiply resistant variants.
Fomivirsen is a phosphorothioate antisense oligionucleotide complementary to the mRNA sequence for the major immediate-early region of CMV and inhibits CMV replication through sequence-specific and nonspecific mechanisms, including inhibition of virus binding to cells. Fomivirsen is active against CMV strains resistant to ganciclovir, foscarnet, and cidofovir.
Fomivirsen is given by intravitreal injection for patients intolerant of or unresponsive to other therapies for CMV retinitis. Following injection, it is cleared from the vitreous humor with a t1/2of ~55 hours through distribution to the retina and probably local exonuclease digestion. In HIV-infected patients with refractory, sight-threatening CMV retinitis, fomivirsen injections (330 ^g weekly for 3 weeks and then every 2 weeks or on days 1 and 15 followed by monthly) significantly delay retinitis progression. Ocular side effects include iritis in up to 25% of patients, which can be managed with topical glucocorticoids, vitritis, cataracts, and increased intraocular pressure in 15-20% of patients. Recent cidofovir use may increase the risk of inflammatory reactions.
Foscarnet chemistry and antiviral activity Foscarnet (trisodium phosphonoformate) is an inorganic pyrophosphate analog that inhibits herpesviruses and HIV.
High concentrations of 0.5-1 mM reversibly inhibit the proliferation of uninfected cells.
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