The treatment of acute herpes zoster requires acyclovir 800 mg orally to be given five times per day for 7 to 10 days. Acyclovir has also been shown to reduce the duration of symptoms of postherpetic neuralgia from 62 days for patients treated with placebo to 20 days for patients treated with acyclovir. One prospective cohort of 14,858 patients treated with oral acyclovir found a 3-month PHN incidence of 2.1%, lower than that for historical controls.
In addition to the oral form, ACV is also available in a topical as well as an intravenous preparation. Topical ACV continues to be used for therapy of HSV regardless of its low efficacy in that form. In immunocompromised patients with HSV or VZV, especially with disseminated disease, as well as in immunocompetent persons with severe trigeminal (especially ophthalmic) zoster, the intravenous form of ACV is preferred. This is because the efficacy of acyclovir is limited, owing to a 15% to 20% bioavailability when taken orally.
Because of the low bioavailability of oral ACV and the frequent dosing schedule, two additional drugs were approved for treatment of herpes. Both of these new drugs provide more convenient dosing and greater bioavailability than does oral acyclovir. Famciclovir (FCV) is the oral prodrug form of the acyclic nucleoside penciclovir, which must be phosphorylated like acyclovir to be active. Penciclovir triphosphate has a much longer intracellular half life than does acyclovir triphosphate (i.e., the T1/2 of penciclovir triphosphate is 10 to 20 hours in HSV-infected cells and 7 hours in VZV-infected cells in contrast to a T1/2 less than 1 hour for acyclovir triphosphate in either HSV-or VSV-infected cells). FCV also has a greater bioavailability than ACV when taken orally, 77% compared with 15% to 20%, respectively. This drug is FDA-approved for the episodic treatment of recurrent genital herpes at a dose of 125 mg twice a day for 5 days. FCV was shown to significantly reduce the symptoms of pain, burning, tenderness, and tingling in patients with recurrent genital herpes. Studies comparing ACV with FCV in the therapy of first episode genital herpes showed similar tolerability and side effects with no significant differences between the two in decreasing the period of viral shedding, time to complete healing, and loss of all symptoms. Recently, FCV at 250 mg twice daily was approved for suppression of recurrent genital herpes. FCV has also been shown to decrease the healing time of cutaneous manifestations of herpes zoster as well as reduce the duration of PHN. FCV is FDA-approved for the therapy of acute herpes zoster at a dose of 500 mg three times daily for 7 days. The topical form of penciclovir is also available and is the first FDA-approved antiviral drug for the episodic treatment of herpes labialis in healthy patients.