What are the recommended oral acyclovir dosing regimens for primary or recurrent labial herpes simplex virus (HSV) infection in healthy adults, immunocompromised patients, children, and patients with renal impairment, including suppressive therapy?

Oral Acyclovir Dosing for Herpes Labialis (Cold Sores)

Acute Treatment of Recurrent Oral Herpes

For recurrent oral herpes (cold sores) in immunocompetent adults, use acyclovir 400 mg orally 3 times daily for 5 days, initiated during prodrome or within 2 days of lesion onset. 1, 2

The CDC provides three equally effective regimens for treating recurrent episodes, all for 5-day duration 1, 2:

• Acyclovir 400 mg orally 3 times daily (most practical dosing)
• Acyclovir 200 mg orally 5 times daily
• Acyclovir 800 mg orally 2 times daily

Timing is critical: Treatment must begin during the prodromal phase or within 48 hours of lesion appearance to achieve meaningful benefit. 1, 2 Starting therapy after this window significantly reduces effectiveness. 2

Expected Clinical Outcomes

The 800 mg twice-daily regimen demonstrates 2:

• Shorter symptom duration (8.1 vs 12.5 days with placebo)
• Reduced pain duration (2.5 vs 3.9 days with placebo)
• Fewer lesions developing (7% vs 26% with placebo)

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Suppressive Therapy for Frequent Recurrences

For patients with ≥6 episodes per year, use acyclovir 400 mg orally twice daily for chronic suppression. 1, 3

This regimen reduces recurrence frequency by ≥75%. 1 In clinical trials, suppressive therapy resulted in a 53% reduction in clinical recurrences and 71% reduction in culture-positive recurrences compared to placebo. 3

Alternative suppressive dosing 1, 4:

• Acyclovir 200 mg orally 3-5 times daily (titrate to lowest effective dose)

Important caveat: Acyclovir neither eradicates latent virus nor affects recurrence frequency after discontinuation. 2 Reassess need for suppression annually. 5

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Pediatric Dosing

For children <45 kg with oral HSV (gingivostomatitis):

Mild Disease

• Acyclovir 20 mg/kg orally 3 times daily (maximum 400 mg/dose) for 5-10 days 6, 1

Moderate to Severe Disease

• Start with acyclovir 5-10 mg/kg IV every 8 hours 6
• Transition to oral acyclovir once lesions begin regressing 6
• Continue until complete healing 6

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Immunocompromised Patients

Immunocompromised patients require higher doses and longer treatment duration. 1, 4

Acute Episodes

• Acyclovir 400 mg orally 3-5 times daily for 7-14 days or until complete resolution 1, 4
• For severe disease requiring hospitalization: acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days 1, 4

Suppressive Therapy

• Acyclovir 400 mg orally 2-3 times daily 1

Critical pitfall: Monitor for acyclovir resistance if lesions persist despite therapy. 1 Acyclovir-resistant HSV requires foscarnet 40 mg/kg IV 3 times daily or 60 mg/kg IV twice daily. 6, 1

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Renal Impairment Dosing

Acyclovir requires dose adjustment in renal insufficiency due to primary renal excretion. 1 Ensure adequate hydration during therapy. 1

Standard adjustments based on creatinine clearance are necessary, though specific dosing tables should be consulted for precise modifications. 7

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Key Clinical Considerations

What NOT to Use

Avoid topical acyclovir as primary therapy - it provides no improvement in systemic symptoms and is significantly less effective than oral formulations. 4, 8, 5 Oral antiviral medications are significantly more effective than topical formulations. 2

Patient Counseling

• Abstain from activities that spread virus while lesions are present (though transmission can occur during asymptomatic periods) 2, 4
• Acyclovir does not prevent future recurrences after discontinuation 2
• Treatment works best when started early 1, 2

Monitoring

• Monitor for neutropenia in children receiving acyclovir (most common toxicity) 1
• Watch for development of resistant viral strains with prolonged use 7, 5