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

Treatment for Cold Sores (Herpes Labialis)

Oral valacyclovir 2g twice daily for 1 day, initiated at the earliest symptom (tingling, itching, or burning), is the recommended first-line treatment for cold sores. 1, 2, 3

Episodic Treatment Regimens

First-Line Oral Therapy

• Valacyclovir 2g twice daily for 1 day (doses taken 12 hours apart) reduces median episode duration by 1.0 day compared to placebo and offers the most convenient dosing schedule 1, 4
• This regimen is FDA-approved and demonstrates high bioavailability with proven efficacy when initiated during prodrome or within 24 hours of symptom onset 3, 4

Alternative Oral Options

• Famciclovir 1500mg as a single dose is equally effective, significantly reducing healing time of primary lesions 1, 2
• Acyclovir 400mg five times daily for 5 days is another option but requires more frequent dosing and lower patient adherence 1, 5

Critical Timing Considerations

• Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (tingling, itching, burning) before visible lesions appear 1, 2, 3
• Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 6, 2
• Efficacy decreases significantly when treatment starts after lesions have fully developed (papule, vesicle, or ulcer stage) 3
• Patient-initiated therapy at first symptoms may even prevent lesion development in some cases 1

Topical Treatments: Limited Role

• Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy 1, 2
• Topical penciclovir cream reduces healing time by only 0.7 days compared to placebo 7
• Topical treatments may be considered for patients who refuse or cannot tolerate oral therapy, but oral antivirals remain superior 6, 1
• Supportive topical measures include white soft paraffin ointment applied every 2 hours and topical anesthetics (benzydamine hydrochloride) for pain management 2

Suppressive Therapy for Frequent Recurrences

Indications

• Patients experiencing 6 or more recurrences per year should be offered suppressive therapy 1, 2
• Also indicated for patients with particularly severe episodes or significant psychological distress from recurrences 1

Suppressive Regimens

• 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 outbreaks 1, 2
• Safety and efficacy documented for acyclovir up to 6 years; valacyclovir and famciclovir 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, 2

Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 6
• Higher doses or longer treatment durations may be required 1
• Acyclovir resistance rates up to 7% in immunocompromised patients (compared to <0.5% in immunocompetent hosts) 1, 2

Pediatric Patients

• Valacyclovir is FDA-approved for cold sores in patients aged ≥12 years 3
• Efficacy and safety not established in children <12 years for herpes labialis 3

Safety Profile

• All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1, 2
• Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate in intensity 1
• Development of resistance when used episodically in immunocompetent patients is rare (<0.5%) 1, 2

Common Pitfalls to Avoid

• Do not rely solely on topical treatments when oral therapy is substantially more effective 1, 2
• Do not start treatment too late—efficacy plummets when initiated after lesions have fully developed 1, 2
• Do not use topical antivirals for suppressive therapy—they cannot reach the site of viral reactivation in sensory ganglia 1, 2
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could benefit significantly 1, 2
• Do not use inadequate dosing—short-course, high-dose therapy (valacyclovir 2g twice daily for 1 day) is more effective than traditional longer courses with lower doses 1, 5

Preventive Counseling

• Identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 6, 2
• Use sunscreen or zinc oxide on lips to decrease probability of recurrent outbreaks 2
• Patients should be informed that antivirals are not a cure for cold sores and that viral shedding can occur asymptomatically 3
• Avoid contact with lesions to prevent transmission to others, especially to immunocompromised individuals and infants 3