What is the recommended adult dose of acyclovir for treating herpes simplex virus infection in patients with normal renal function?

Acyclovir Dosing for Herpes Simplex Virus Infection

For adults with normal renal function, acyclovir dosing depends on the type and severity of HSV infection: oral acyclovir 400 mg three times daily for 5-10 days treats initial genital herpes, 400 mg three times daily or 800 mg twice daily for 5 days treats recurrent episodes, and intravenous acyclovir 5-10 mg/kg every 8 hours is reserved for severe disease requiring hospitalization. 1, 2

Initial Episode of Genital Herpes

For first clinical episodes of genital HSV, the CDC recommends:

• Acyclovir 400 mg orally three times daily for 7-10 days 2
• Alternative: Acyclovir 200 mg orally five times daily for 7-10 days 2
• Treatment may be extended beyond 10 days if healing is incomplete 2

The FDA label confirms that oral acyclovir 200 mg five times daily for 5 days is effective for initial genital herpes, significantly reducing viral shedding, new lesion formation, and duration of symptoms 3, 4

Recurrent Genital Herpes Episodes

For recurrent genital HSV outbreaks, the CDC recommends episodic treatment with:

• Acyclovir 400 mg orally three times daily for 5 days 1, 2
• Acyclovir 800 mg orally twice daily for 5 days 1, 2
• Alternative: Acyclovir 200 mg orally five times daily for 5 days 2

Initiate therapy during the prodrome or within 24 hours of lesion onset for maximum efficacy, as peak viral titers occur in the first 24 hours 1, 2

A shorter 2-day course of acyclovir 800 mg three times daily has demonstrated efficacy in reducing lesion duration and viral shedding, offering a convenient alternative 5

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, the CDC recommends daily suppressive therapy:

• Acyclovir 400 mg orally twice daily 1, 6, 2
• This regimen reduces recurrence frequency by ≥75% 1, 6
• Safety and efficacy documented for up to 6 years of continuous use 6
• After 1 year, consider discontinuation to reassess recurrence frequency 6, 2

Orofacial Herpes (Cold Sores)

For mild symptomatic gingivostomatitis or cold sores:

• Acyclovir 400 mg orally five times daily for 5 days 1, 6
• Alternative: Acyclovir 20 mg/kg (maximum 400 mg/dose) orally three times daily for 5-10 days in children <45 kg 7, 1

For moderate to severe gingivostomatitis requiring hospitalization:

• Acyclovir 5-10 mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy and continue until complete healing 7, 1

Severe or Complicated HSV Infections

For severe disease requiring hospitalization, disseminated infection, or CNS involvement:

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical improvement 1, 3
• For HSV encephalitis: Acyclovir 10 mg/kg IV every 8 hours for 10-21 days 7, 3
• For neonatal CNS or disseminated disease: Acyclovir 20 mg/kg IV every 8 hours for 21 days 7

The FDA label confirms that IV acyclovir at 5 mg/kg every 8 hours achieves steady-state peak concentrations of 9.8 mcg/mL, while 10 mg/kg every 8 hours achieves 22.9 mcg/mL 3

Special Populations and Considerations

Immunocompromised Patients

• Higher doses may be required: Acyclovir 400 mg orally 3-5 times daily 1
• Longer treatment duration (14 days or until complete resolution) 1
• Acyclovir resistance occurs in ~7% of immunocompromised patients versus <0.5% in immunocompetent hosts 1, 6

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant infection:

• Foscarnet 40 mg/kg IV every 8 hours or 60 mg/kg IV twice daily 7, 1

Renal Impairment

Dose adjustment is mandatory in renal dysfunction, as acyclovir is primarily renally excreted (62-91% unchanged) 3:

• Creatinine clearance >80 mL/min: No adjustment needed (half-life 2.5 hours) 3
• Creatinine clearance 50-80 mL/min: Half-life increases to 3 hours 3
• Creatinine clearance 15-50 mL/min: Half-life increases to 3.5 hours 3
• Anuric patients: Half-life increases to 19.5 hours 3

Always assess renal function before initiating therapy, especially in elderly patients (≥80 years), to avoid drug accumulation and neurotoxicity 1

Critical Pitfalls to Avoid

• Do not use topical acyclovir as primary therapy—it is substantially less effective than oral therapy and provides no improvement in systemic symptoms 2, 8, 9
• Do not delay treatment—efficacy decreases significantly when initiated after the first 24 hours of symptom onset 1, 2
• Do not stop therapy at a fixed interval—continue until all lesions are fully crusted and healed 1
• Do not assume suppressive therapy eliminates transmission risk—asymptomatic viral shedding persists despite treatment 1, 6, 2