What is the recommended dosing for antiviral medication (e.g. acyclovir, valacyclovir, famciclovir) in an otherwise healthy adult with recurrent cold sores (herpes simplex labialis)?

Antiviral Dosing for Cold Sores (Herpes Labialis)

For episodic treatment of cold sores in healthy adults, first-line therapy is famciclovir 1500 mg as a single dose OR valacyclovir 2 grams twice daily for 1 day, both initiated at the earliest sign of symptoms (tingling, itching, burning). 1, 2

Episodic Treatment Options

First-Line: Single-Dose Regimens (Most Convenient)

• Famciclovir 1500 mg as a single dose - FDA-approved, taken at first symptom 2
• Valacyclovir 2 grams twice daily for 1 day (two doses 12 hours apart) - reduces episode duration by 1.0 day compared to placebo 1

Alternative: Multi-Day Regimens

• Acyclovir 400 mg five times daily for 5 days - requires more frequent dosing but effective 1, 3

Critical timing consideration: Treatment must be initiated during the prodromal phase (tingling, itching, burning) or within 24-48 hours of lesion onset for optimal efficacy, as peak viral titers occur in the first 24 hours after lesion onset. 1, 4

Chronic Suppressive Therapy

For patients with ≥6 recurrences per year, severe outbreaks, or significant psychological distress, daily suppressive therapy is indicated. 1

Suppressive Dosing Options

• Valacyclovir 500 mg once daily (can increase to 1000 mg once daily for very frequent recurrences) 1
• Famciclovir 250 mg twice daily 1, 2
• Acyclovir 400 mg twice daily 1

Suppressive Therapy Efficacy and Duration

• Daily suppressive therapy reduces recurrence frequency by ≥75% 1
• Safety documented for acyclovir up to 6 years; valacyclovir and famciclovir documented for 1 year 1
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence rate, as frequency decreases over time in many patients 1

Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the entire oral cavity or extending across the face 1, 4
• May require higher doses or longer treatment durations 1
• Acyclovir resistance rates are higher (7% vs <0.5% in immunocompetent patients) 5, 1

Severe Intraoral HSV or Gingivostomatitis

• Acyclovir 5-10 mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy 1
• For mild symptomatic gingivostomatitis: Acyclovir 20 mg/kg (maximum 400 mg/dose) orally 3 times daily for 5-10 days 1

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant cold sores (rare in immunocompetent hosts at <0.5%), foscarnet 40 mg/kg IV three times daily is the treatment of choice. 1, 6

• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative 1

Renal Impairment Dosing

Dose adjustments are mandatory for patients with renal impairment to prevent acute renal failure. 2

Famciclovir Adjustments for Herpes Labialis (Single Dose)

• CrCl ≥60 mL/min: 1500 mg single dose 2
• CrCl 40-59 mL/min: 750 mg single dose 2
• CrCl 20-39 mL/min: 500 mg single dose 2
• CrCl <20 mL/min: 250 mg single dose 2
• Hemodialysis: 250 mg following each dialysis 2

Common Pitfalls to Avoid

• Do not rely on topical antivirals as primary therapy - they are substantially less effective than oral therapy and cannot reach the site of viral reactivation in sensory ganglia 1, 4
• Do not delay treatment - efficacy decreases significantly when initiated after lesions have fully developed; treatment during prodrome may even prevent lesion development 1
• Do not use herpes zoster (shingles) dosing for cold sores - HSV-1 requires different regimens than VZV 7, 2
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1

Safety Profile

• All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1
• Most common side effects: headache (<10%), nausea (<4%), and diarrhea - typically mild to moderate 1, 2
• Despite increasing use, resistance remains low (<0.5% in immunocompetent hosts) 5, 1