What is the treatment for cold sores?

Treatment of Cold Sores (Herpes Labialis)

For cold sores, initiate high-dose valacyclovir 2g twice daily for 1 day at the earliest sign of symptoms (prodrome), which reduces episode duration by approximately 1 day compared to placebo. 1, 2

First-Line Oral Antiviral Therapy

Episodic Treatment (Patient-Initiated at First Symptoms):

• Valacyclovir 2g twice daily for 1 day is the preferred first-line treatment, offering the most convenient dosing with proven efficacy 1, 3, 2
• Famciclovir 1500mg as a single dose is an equally effective alternative with comparable convenience 1
• Acyclovir 400mg five times daily for 5 days is another option but requires more frequent dosing and is less convenient 1, 3

Critical timing consideration: Treatment must be initiated during the prodromal phase (tingling, itching, burning) or within 24 hours of lesion appearance for maximum benefit 1. Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 1. Efficacy decreases significantly when treatment is initiated after lesions have fully developed 1.

Suppressive Therapy for Frequent Recurrences

Indications for daily suppressive therapy include: 1

• Six or more recurrences per year
• Particularly severe, frequent, or complicated disease
• Significant psychological distress from recurrences

Suppressive therapy regimens: 1

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

Efficacy and duration: Daily suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent recurrences 1. Safety and efficacy have been documented for acyclovir for up to 6 years, while valacyclovir and famciclovir have documented safety for 1 year of continuous use 1. After 1 year of continuous suppressive therapy, consider discontinuation to reassess the patient's recurrence rate, as frequency decreases over time in many patients 1.

Topical Therapy (Limited Role)

• Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy 1, 3
• Topical acyclovir 5% with hydrocortisone 1% (ME-609) applied 5 times daily for 5 days prevented progression to ulcerative lesions in 42% of patients versus 26% with placebo, but still inferior to oral therapy 4
• Topical antivirals are not effective for suppressive therapy as they cannot reach the site of viral reactivation in the trigeminal ganglion 1

Special Populations

Immunocompromised patients: 1

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

Pediatric patients ≥12 years: Valacyclovir is FDA-approved for treatment of cold sores in this age group 3

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is significantly more effective 1
• Starting treatment too late after lesions have fully developed, when efficacy is substantially reduced 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
• Using inadequate dosing regimens rather than the proven short-course, high-dose therapy 1

Preventive Counseling

• Patients should identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 1
• Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1