What is the recommended dosing for Acyclovir (Antiviral medication) in the treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections?

Acyclovir Dosing for HSV and VZV Infections

Genital Herpes Simplex Virus (HSV)

First Clinical Episode

For initial genital herpes, use acyclovir 400 mg orally three times daily for 7-10 days, which provides optimal balance of efficacy and convenience. 1, 2

Alternative regimens include:

• Acyclovir 200 mg orally five times daily for 7-10 days 3, 1, 2
• Treatment may be extended beyond 10 days if healing is incomplete 1

For first-episode herpes proctitis specifically, use acyclovir 400 mg orally five times daily for 10 days. 3

Recurrent Episodes

For recurrent genital herpes, use acyclovir 800 mg orally twice daily for 5 days, as this provides the most convenient dosing schedule with equivalent efficacy. 1, 4, 2

Alternative regimens include:

• Acyclovir 400 mg orally three times daily for 5 days 3, 1, 4
• Acyclovir 200 mg orally five times daily for 5 days 3, 1, 4

Initiate therapy during prodrome or within 1 day of lesion onset for maximum benefit. 1, 4 Starting treatment after 2 days provides limited benefit in immunocompetent patients. 3, 4

Chronic Suppressive Therapy

For patients with frequent recurrences (≥6 episodes per year), use acyclovir 400 mg orally twice daily for up to 12 months. 1, 5, 2

• This regimen reduces recurrence frequency by ≥75% 1, 5
• Alternative dosing: 200 mg orally 3-5 times daily, titrated to the lowest effective dose 3, 5, 2
• After 1 year of continuous therapy, discontinue acyclovir to reassess the patient's recurrence rate 3, 5, 2

Critical caveat: Suppressive therapy reduces but does not eliminate asymptomatic viral shedding or transmission risk. 1, 5

Herpes Zoster (Shingles)

For acute herpes zoster, use acyclovir 800 mg orally every 4 hours (5 times daily) for 7-10 days. 2

• Initiate therapy within 72 hours of rash onset for optimal efficacy 2
• Intravenous acyclovir is indicated for immunocompromised patients with varicella-zoster 2

Varicella (Chickenpox)

For children ≥2 years and ≤40 kg: use acyclovir 20 mg/kg per dose orally four times daily (maximum 80 mg/kg/day) for 5 days. 2

For adults and children >40 kg: use acyclovir 800 mg orally four times daily for 5 days. 2

• Initiate therapy within 24 hours of symptom onset—efficacy data beyond this window are lacking 2
• Intravenous acyclovir is indicated for immunocompromised patients 2

Orolabial Herpes (Cold Sores)

For recurrent oral herpes, use acyclovir 400 mg orally three times daily for 5 days, initiated during prodrome or within 2 days of lesion onset. 4

Alternative regimens:

• Acyclovir 800 mg orally twice daily for 5 days 4
• Acyclovir 200 mg orally five times daily for 5 days 4

Important limitation: Most immunocompetent patients with recurrent oral herpes experience limited benefit from therapy. 4 Oral formulations are significantly more effective than topical preparations. 4

Special Populations

Immunocompromised/HIV-Infected Patients

These patients often require higher doses and longer treatment courses than standard regimens. 3, 6

• For suppression: acyclovir 400 mg orally 3-5 times daily 5
• Monitor closely for treatment failure and slower healing 3
• If standard therapy fails after 5-7 days, suspect acyclovir resistance—obtain viral cultures with susceptibility testing and consider foscarnet 40 mg/kg IV three times daily or 60 mg/kg IV twice daily 6

Renal Impairment

Dose adjustment is mandatory based on creatinine clearance: 2

For 200 mg every 4 hours regimen:

• CrCl >10: No adjustment needed
• CrCl 0-10: 200 mg every 12 hours 2

For 400 mg every 12 hours regimen:

• CrCl >10: No adjustment needed
• CrCl 0-10: 200 mg every 12 hours 2

For 800 mg every 4 hours regimen:

• CrCl >25: No adjustment needed
• CrCl 10-25: 800 mg every 8 hours
• CrCl 0-10: 800 mg every 12 hours 2

For hemodialysis patients: administer an additional dose after each dialysis session. 2

Critical Pitfalls to Avoid

Never use topical acyclovir as primary therapy—it is substantially less effective than oral formulations and provides no improvement in systemic symptoms. 3, 1, 7

Do not promise patients that acyclovir will cure herpes or prevent future recurrences after discontinuation—it neither eradicates latent virus nor affects subsequent recurrence risk. 3, 4

Avoid high-dose valacyclovir (8 g/day) in immunocompromised patients due to association with hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. 5

Do not continue suppressive therapy indefinitely without reassessment—the natural history of genital herpes changes over time, and many patients experience decreased recurrence frequency. 3, 2