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

Treatment for Cold Sores (Herpes Labialis)

For acute cold sore episodes, initiate valacyclovir 2g twice daily for 1 day at the first sign of symptoms (during the prodromal stage or within 24 hours of onset) as first-line therapy. 1, 2

First-Line Oral Antiviral Options for Acute Episodes

Valacyclovir is the preferred first-line treatment due to its superior bioavailability (3-5 times higher than acyclovir), convenient single-day dosing, and FDA approval for cold sores. 1, 2, 3

• Valacyclovir 2g twice daily for 1 day reduces median episode duration by 1.0 day compared to placebo and accelerates healing time. 1, 3
• Famciclovir 1500mg as a single dose is an equally effective alternative with single-day dosing, reducing median healing time from 6.2 to 4.4 days. 1, 4, 5
• 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

Treatment must be initiated within 24 hours of symptom onset—ideally during the prodromal phase (itching, burning, tingling)—for maximum effectiveness. 1, 6

• Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication. 7, 1
• Efficacy decreases significantly when treatment is initiated after lesions have fully developed beyond the papule stage. 1, 2
• Patient-initiated therapy at first symptoms may prevent lesion development in some cases. 1

Suppressive Therapy for Frequent Recurrences

Consider daily suppressive therapy for patients experiencing 6 or more recurrences per year. 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

Efficacy and Duration:

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

Topical Treatments: Limited Role

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

• Topical antivirals are not effective for suppressive therapy as they cannot reach the site of viral reactivation in sensory ganglia. 1
• One exception: The combination of topical acyclovir 5% plus hydrocortisone 1% (ME-609) prevented progression to ulcerative lesions in 42% of patients versus 26% with placebo when applied 5 times daily for 5 days. 8

Special Populations

Immunocompromised Patients:

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

Pediatric Patients (≥12 years):

• Valacyclovir 2g twice daily for 1 day is FDA-approved and recommended for children aged 12 years and older. 9, 2
• Oral antivirals are generally well-tolerated with minimal adverse events (headache, nausea, mild GI disturbances). 9

Preventive Measures

• Counsel patients to identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation. 7, 1
• Application of sunscreen may help decrease the probability of UV-induced recurrent outbreaks. 7, 10

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, which are typically mild to moderate. 1
• Resistance to oral antiviral agents when used episodically in immunocompetent patients is unlikely (<0.5%). 1
• Dose adjustments required for patients with renal impairment. 1

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is more effective 1
• Starting treatment too late—efficacy decreases significantly after the first 24 hours 1, 6
• Using topical antivirals for suppressive therapy, which is ineffective 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
• Inadequate dosing—not using short-course, high-dose therapy which is more effective than traditional longer courses 1