What is the recommended dosage of Acyclovir for treating herpes simplex virus infections?

Acyclovir Dosing for Herpes Simplex Virus Infections

For herpes simplex infections, oral acyclovir is strongly preferred over topical formulations, with specific dosing dependent on whether the infection is a first episode, recurrent outbreak, or requires suppressive therapy. 1

Oral Herpes (Herpes Labialis/Cold Sores)

The CDC recommends three equally effective oral regimens for recurrent oral herpes, all administered for 5 days: 2

• Acyclovir 800 mg orally twice daily (most convenient, best adherence) 2
• Acyclovir 400 mg orally three times daily 2
• Acyclovir 200 mg orally five times daily 2

Critical Timing

• Treatment must be initiated during prodrome or within 2 days of lesion onset for maximum benefit—starting after this window significantly reduces effectiveness 1, 2
• The 800 mg twice-daily regimen reduces symptom duration from 12.5 to 8.1 days and pain duration from 3.9 to 2.5 days 2

Genital Herpes

First Clinical Episode

• Acyclovir 200 mg orally 5 times daily for 7-10 days until clinical resolution 1, 3
• For severe disease requiring hospitalization: acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days 3, 4

Recurrent Episodes

The CDC provides three equally effective options, all for 5 days: 1, 3

• Acyclovir 800 mg orally twice daily 1
• Acyclovir 400 mg orally three times daily 1
• Acyclovir 200 mg orally five times daily 1

Chronic Suppressive Therapy

• For patients with ≥6 recurrences per year: acyclovir 400 mg orally twice daily 3
• Alternative: 200 mg orally 3-5 times daily, titrating to the lowest effective dose 3
• Suppressive therapy reduces recurrence frequency by at least 75% 3
• Long-term suppression for up to 5-10 years is safe and effective, with resistance rates <0.5% in immunocompetent patients 5, 6

Immunocompromised Patients

These patients require more aggressive therapy due to risk of prolonged, extensive disease: 1

• Acyclovir 400 mg orally 3-5 times daily for mild-moderate disease 1
• Acyclovir 5-10 mg/kg IV every 8 hours for severe, disseminated, or CNS involvement 1, 4
• Treatment duration typically 7-10 days or until clinical resolution 4
• Resistance rates are higher (~5%) in immunocompromised populations 5

Herpes Simplex Encephalitis

• Acyclovir 10 mg/kg IV every 8 hours for 10 days 4
• This regimen reduces 12-month mortality from 59% to 25% compared to vidarabine 4
• Patients <30 years with less severe neurologic involvement have the best outcomes 4

Neonatal Herpes Simplex

• Acyclovir 10 mg/kg IV every 8 hours for 10 days 4
• Outcomes are superior to vidarabine for localized (SEM) and CNS disease 4

Renal Dosing Adjustments

Acyclovir clearance is highly dependent on renal function—dose adjustment is mandatory: 4

• CrCl >80 mL/min: Standard dosing, half-life 2.5 hours 4
• CrCl 50-80 mL/min: Half-life 3 hours 4
• CrCl 15-50 mL/min: Half-life 3.5 hours 4
• Anuric patients: Half-life 19.5 hours—significant dose reduction required 4

Critical Caveats and Common Pitfalls

Topical Acyclovir Should Be Avoided

• The CDC explicitly discourages topical acyclovir (5% cream) because it is substantially less effective than oral formulations 1
• Topical therapy provides no improvement in systemic symptoms 3

Patient Counseling Points

• Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation 1, 2
• Patients should abstain from activities that spread virus while lesions are present, though transmission can occur during asymptomatic periods 1, 2
• Most immunocompetent patients with recurrent disease experience limited benefit from therapy overall 1, 2

Resistance Management

• In immunocompetent patients with poor response, increase to acyclovir 800 mg orally five times daily before switching agents 7
• If no response after 5-7 days, acyclovir-resistant HSV is likely—consider foscarnet 40 mg/kg IV three times daily or 60 mg/kg twice daily 7
• Alternative for resistant cases: topical trifluridine or IV/topical cidofovir 7

Special Populations

• Geriatric patients: Higher plasma concentrations due to age-related renal decline—dose reduction often required 4
• Pediatric patients (3 months-16 years): 10 mg/kg and 20 mg/kg every 8 hours achieve similar concentrations to adult 5 mg/kg and 10 mg/kg dosing 4
• Neonates (birth-3 months): Clearance is significantly reduced (4.46 mL/min/kg vs 8.44 mL/min/kg in older children), requiring careful dosing 4