What is the treatment for cold sores (herpes simplex labialis)?

Treatment of Cold Sores (Herpes Labialis)

For acute cold sore treatment, use valacyclovir 2g twice daily for 1 day, initiated at the first sign of symptoms (prodrome or within 24 hours of onset). 1, 2, 3

First-Line Oral Antiviral Therapy

Valacyclovir is the preferred first-line agent due to its superior convenience with single-day dosing and proven efficacy, reducing median episode duration by 1.0 day compared to placebo (p=0.001). 1, 2, 4

• Dosing: Valacyclovir 2g twice daily for 1 day (total of 2 doses, 12 hours apart) 1, 2, 3
• This regimen is FDA-approved for cold sores in adults and children ≥12 years 3
• Treatment must be initiated during prodrome or within 24 hours of symptom onset for maximum benefit 1, 2

Alternative First-Line Option

Famciclovir 1500mg as a single dose is equally effective if valacyclovir is unavailable or not tolerated. 1, 2, 5

• Reduces median healing time to 4.4 days versus 6.2 days with placebo (median difference 1.3 days) 5
• Single-dose convenience may improve adherence 1, 5

Traditional Regimen (Less Preferred)

Acyclovir 400mg five times daily for 5 days is effective but requires more frequent dosing and longer treatment duration, making it less convenient than valacyclovir or famciclovir. 1, 6

Critical Timing Considerations

Peak viral titers occur within the first 24 hours after lesion onset, making early intervention essential for blocking viral replication. 1, 6

• Efficacy decreases significantly when treatment starts after lesions progress beyond erythema to vesicles or ulcers 1, 6
• Patient-initiated therapy at first symptoms (tingling, burning, itching) may prevent lesion development in some cases 1
• The FDA label specifically notes that efficacy after clinical signs develop (papule, vesicle, ulcer) has not been established 3

Topical Treatments: Limited Role

Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy. 1, 2

• Topical agents cannot reach the site of viral reactivation in nerve ganglia, making them ineffective for prophylaxis 1, 2
• Consider topical therapy only if oral antivirals are contraindicated or unavailable 1, 2

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, initiate daily suppressive therapy to reduce outbreak frequency by ≥75%. 1

Suppressive Regimen Options:

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

Duration and Monitoring:

• Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1
• Acyclovir has documented safety for up to 6 years 1, 6
• After 1 year of suppressive therapy, consider a trial off medication to reassess recurrence frequency, as episodes often decrease over time 1, 6

Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
• Higher doses or longer treatment durations may be required 1, 2
• Acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 1
• For confirmed acyclovir-resistant HSV, use IV foscarnet 40mg/kg three times daily 1

Renal Impairment

• Dose adjustments required based on creatinine clearance for all oral antivirals 1, 2

Common Pitfalls to Avoid

• Starting treatment too late: Efficacy plummets after lesions fully develop beyond erythema stage 1, 6
• Relying on topical treatments: Oral antivirals are significantly more effective 1, 2
• Using traditional 5-day acyclovir regimens: Short-course, high-dose therapy (valacyclovir or famciclovir) offers superior convenience and adherence 1, 6
• Not considering suppressive therapy: Patients with ≥6 recurrences per year could significantly benefit 1
• Failing to counsel on triggers: Patients should identify and avoid personal triggers including UV light exposure, stress, fever, and menstruation 1

Safety Profile

All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events. 1

• Common side effects include headache (<10%), nausea (<4%), and diarrhea, typically mild to moderate in intensity 1
• Resistance remains low (<0.5%) in immunocompetent hosts when used episodically 1