Antiherpetic Agents

GENERAL PRINCIPLES

Antiherpetic agents are nucleotide analogs that inhibit viral DNA synthesis. All antiherpetic agents require dose adjustment for renal dysfunction. For ease of classification, antiherpetic agents include those that cover herpes simplex virus (HSV) 1 and 2, and varicella-zoster virus (VZV).

TREATMENT

• Acyclovir (400 mg PO q8h for HSV, 800 mg PO five times a day for localized VZV infections, 5-10 mg/kg IV q8h for severe HSV infections, and 10 mg/kg IV q8h for severe VZV infections and HSV encephalitis) is active against HSV and VZV. It is indicated for treatment of primary and recurrent genital herpes, severe herpetic stomatitis, and HSV encephalitis. Acyclovir can be used as prophylaxis in patients who have frequent HSV recurrences (400 mg PO q12h). It is also used for HSV ophthalmicus, disseminated primary VZV in adults (significant morbidity compared to the childhood illness), and severe disseminated primary VZV in children. IV acyclovir should be dosed using IBW in patients with obesity.

Adverse events. Reversible crystalline nephropathy may occur; preexisting renal failure, dehydration, and IV bolus dosing increase the risk of this effect. Rare cases of CNS disturbances, including delirium, tremors, and seizures, may also occur, particularly with high doses in patients with renal failure and in the elderly.

• Valacyclovir (1000 mg PO q8h for VZV, 1000 mg PO q12h for initial episode of genital HSV, and 500 mg PO q12h or 1000 mg PO q24h for suppression of recurrent episodes of genital HSV) is an orally administered prodrug of acyclovir used for the treatment and prevention of HSV infections and for treatment of VZV. Valacyclovir's bioavailability is roughly three to five times higher than oral acyclovir, resulting in less frequent dosing. A 1000 mg oral dose of valacyclovir is equivalent to 5 mg/kg of IV acyclovir.

Adverse events include GI upset, headache, rash, and rarely CNS disturbances. High doses (8 g/d) have been associated with development of hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura in immunocompromised patients.

• Famciclovir (500 mg PO q8h for VZV, 250 mg PO q8h for the initial episode of genital HSV infection, and 250 mg PO q12h for suppression of recurrent episodes of genital HSV) is an orally administered antiviral agent used for the treatment of acute VZV reactivation and for treatment or suppression of genital HSV infections.

Adverse events include headache, nausea, and diarrhea.