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

Cold Sore Treatment

First-Line Treatment Recommendation

For episodic treatment of cold sores, initiate valacyclovir 2g twice daily for 1 day at the earliest sign of symptoms (during the prodromal phase), which reduces episode duration by approximately 1 day and offers the most convenient dosing regimen. 1, 2, 3, 4

Treatment Algorithm by Clinical Scenario

Episodic Treatment (Infrequent Outbreaks)

Preferred regimen:

• Valacyclovir 2g twice daily for 1 day - This is the CDC-recommended first-line option with the highest convenience and proven efficacy 1, 2, 3, 4

Alternative regimens (in order of preference):

• Famciclovir 1500mg as a single dose OR 750mg twice daily for 1 day 1, 2
• Acyclovir 400mg five times daily for 5 days (less convenient due to frequent dosing) 1, 2

Suppressive Therapy (≥6 Recurrences Per Year)

Indications for daily suppressive therapy: 1

• Six or more recurrences annually
• Severe, frequent, or complicated disease
• Significant psychological distress from recurrences

Suppressive regimen options (CDC-recommended): 1

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

Expected benefit: Daily suppressive therapy reduces recurrence frequency by ≥75% 1

Critical Timing Considerations

Treatment must be initiated as early as possible - ideally during the prodromal phase (itching, burning, tingling) or within the first 24 hours of lesion appearance, as peak viral titers occur in the first 24 hours after lesion onset 5, 1, 2. Efficacy decreases significantly when treatment is delayed beyond this window 1, 2, 3.

Patient-initiated therapy at first symptoms may even prevent lesion development in some cases 1.

Topical vs. Oral Therapy

Oral antivirals are strongly preferred over topical treatments. 1

• Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy 1
• Topical agents cannot reach the site of viral reactivation in sensory ganglia, making them ineffective for suppressive therapy 1
• The combination of topical acyclovir plus hydrocortisone showed no significant advantage over acyclovir alone in preventing ulceration or reducing episode duration 6, 7

Duration and Monitoring of Suppressive Therapy

Safety data: 1

• Acyclovir: documented safety up to 6 years
• Valacyclovir and famciclovir: documented safety for 1 year of continuous use

After 1 year of continuous suppressive therapy, consider a trial off therapy to reassess recurrence frequency, as recurrence rates decrease over time in many patients 1, 2.

Lesion Management

For intact blisters, gently pierce at the base with a sterile needle to drain fluid while keeping the roof intact as a biological dressing 2. Apply petroleum jelly or bland emollient to support barrier function and encourage healing 2.

Special Populations

Immunocompromised patients: 5, 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
• Acyclovir resistance rates up to 7% in this population (vs. <0.5% in immunocompetent hosts)
• For acyclovir-resistant HSV, foscarnet 40mg/kg IV three times daily is recommended

Pediatric patients: 3

• Valacyclovir is FDA-approved for cold sores in patients ≥12 years of age
• Efficacy and safety not established in children <12 years for cold sores

Preventive Counseling

Counsel patients to identify and avoid personal triggers: 5, 1

• Ultraviolet light exposure (recommend sunscreen or zinc oxide application)
• Fever
• Psychological stress
• Menstruation

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%)
• Diarrhea

These are typically mild to moderate in intensity 1.

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is significantly more effective 1
• Starting treatment too late - efficacy decreases dramatically after the first 24 hours 1, 2
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could benefit from 75% reduction in outbreak frequency 1
• Using inadequate dosing - short-course, high-dose therapy (valacyclovir 2g twice daily for 1 day) is more effective and convenient than traditional longer courses 1, 4
• Not discussing trigger avoidance even while on suppressive therapy 1