What is the best treatment for a cold sore?

Best Treatment for Cold Sores

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

First-Line Oral Antiviral Therapy

Valacyclovir is the preferred first-line treatment due to its superior convenience, high bioavailability, and proven efficacy 1, 2:

• Valacyclovir 2g twice daily for 1 day reduces median episode duration by 1.0 day compared to placebo and is the CDC-recommended regimen 1, 3
• This single-day, high-dose regimen offers greater convenience and improved adherence compared to traditional longer courses 1
• Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (tingling, burning sensation) when peak viral titers occur 1, 2

Alternative Oral Antivirals

If valacyclovir is unavailable, use these alternatives 1, 2:

• Famciclovir 1500mg as a single dose - equally effective with convenient single-day dosing 1
• Acyclovir 400mg five times daily for 5 days - requires more frequent dosing but remains effective 1, 2

Topical Treatments: Limited Role

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

• Topical docosanol (for ages ≥12 years) can be used but expect minimal benefit 4
• Apply supportive measures: white soft paraffin ointment every 2 hours, topical anesthetics for pain, and antiseptic oral rinses to reduce bacterial colonization 2

Critical Timing Considerations

Early intervention is essential because 1, 2:

• Peak viral titers occur within the first 24 hours after lesion onset 1, 2
• Efficacy decreases significantly when treatment starts after lesions fully develop 1, 2
• Patient-initiated therapy at first symptoms may prevent lesion development entirely in some cases 1

Suppressive Therapy for Frequent Recurrences

Consider daily suppressive therapy if experiencing ≥6 recurrences per year 1, 2:

• Valacyclovir 500mg once daily (increase to 1000mg daily for very frequent recurrences) 1, 2
• Alternative: Famciclovir 250mg twice daily or Acyclovir 400mg twice daily 1
• Daily suppressive therapy reduces recurrence frequency by ≥75% 1, 2
• After 1 year of continuous therapy, consider discontinuation to reassess recurrence rate, as frequency naturally decreases over time in many patients 1

Special Populations

Pediatric patients (≥12 years): Valacyclovir 2g twice daily for 1 day is FDA-approved and recommended 5, 6

Immunocompromised patients: Higher doses or longer treatment durations may be required, with acyclovir resistance rates up to 7% (versus <0.5% in immunocompetent patients) 1:

• For confirmed acyclovir-resistant HSV: Foscarnet 40mg/kg IV three times daily 1

Pregnancy and lactation: Valacyclovir has limited human data showing 3.9-4.5% major birth defect rate during exposure; acyclovir (valacyclovir's metabolite) is present in breast milk at levels providing approximately 0.6mg/kg/day to the breastfed infant 6

Common Pitfalls to Avoid

• Never rely solely on topical treatments when oral therapy is far more effective 1, 2
• Don't start treatment too late - efficacy plummets after lesions fully develop 1, 2
• Never use topical antivirals for suppressive therapy - they cannot reach the viral reactivation site in sensory ganglia 1, 2
• Don't overlook suppressive therapy in patients with ≥6 recurrences per year who could benefit substantially 1, 2

Preventive Counseling

Advise patients to identify and avoid personal triggers 2, 5:

• Ultraviolet light exposure (use sunscreen or zinc oxide) 2
• Fever, psychological stress, menstruation 2, 5

Safety Profile

Oral antivirals are generally well-tolerated with minimal adverse events 1, 2:

• Common side effects: headache (<10%), nausea (<4%), mild diarrhea 1
• Resistance development with episodic use in immunocompetent patients is rare (<0.5%) 1, 2