What is the recommended treatment for a patient presenting with a cold sore (herpes simplex labialis)?

Treatment for Cold Sores (Herpes Labialis)

For cold sores, start oral valacyclovir 2g twice daily for 1 day at the first sign of symptoms (tingling, itching, burning), which reduces episode duration by 1 day compared to placebo. 1, 2

First-Line Oral Antiviral Options

Oral antivirals are superior to topical treatments and should be the standard of care. 3, 4

Recommended Regimens (in order of convenience):

• Valacyclovir 2g twice daily for 1 day - Most convenient single-day regimen, FDA-approved, reduces median episode duration by 1.0 day 1, 2
• Famciclovir 1500mg as a single dose - Alternative single-dose option, significantly reduces healing time 5, 4
• Acyclovir 400mg five times daily for 5 days - Effective but requires more frequent dosing and longer duration 3, 4

Critical Timing for Treatment

Initiate therapy at the first symptom (prodrome stage: tingling, itching, burning, pain) or within 24 hours of lesion appearance. 1, 5, 4

• Peak viral titers occur within the first 24 hours after lesion onset, making early intervention essential 4
• Efficacy decreases significantly when treatment starts after lesions fully develop 4
• Treatment initiated after papule, vesicle, or ulcer formation has not been established as effective by FDA 1

Why Oral Therapy Over Topical

Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy. 3, 4

• Topical agents reduce symptom duration by less than 1 day with frequent application (5-6 times daily) 3
• Topical antivirals cannot reach the site of viral reactivation in nerve ganglia 3, 4
• OTC topical anesthetics and zinc-based creams have inconclusive evidence 3

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, initiate daily suppressive therapy. 4

Suppressive Regimen Options:

• Valacyclovir 500mg once daily (can increase to 1000mg for very frequent recurrences) 4
• Famciclovir 250mg twice daily 4, 5
• Acyclovir 400mg twice daily 4

Suppressive Therapy Efficacy and Duration:

• Reduces recurrence frequency by ≥75% 4
• Safety documented for acyclovir up to 6 years, valacyclovir and famciclovir for 1 year 4
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence rate, as frequency naturally decreases over time in many patients 4

Special Populations

Immunocompromised Patients:

• Episodes are typically longer and more severe, potentially involving oral cavity or extending across face 4
• Higher acyclovir resistance rates (7% vs <0.5% in immunocompetent patients) 4
• May require higher doses or longer treatment durations 4
• For HIV-infected patients with recurrent orolabial herpes: famciclovir 500mg twice daily for 7 days 5

Pediatric Patients:

• Valacyclovir approved for cold sores in patients ≥12 years old 1
• Efficacy not established in children <12 years 1

Renal Impairment:

• Dose adjustments required based on creatinine clearance 5
• For valacyclovir single-dose regimen: reduce to 1500mg single dose if CrCl 30-49 mL/min, 500mg single dose if CrCl 10-29 mL/min 5

Acyclovir-Resistant HSV

For confirmed acyclovir-resistant HSV (rare at <0.5% in immunocompetent hosts), use IV foscarnet 40mg/kg three times daily. 4

• Resistance more common in immunocompromised patients (up to 7%) 3, 4
• Cross-resistance occurs with all oral antivirals (acyclovir, valacyclovir, famciclovir) 3

Adjunctive Therapies

• Topical acyclovir 5%/hydrocortisone 1% cream applied 5-6 times daily may provide additional benefit by reducing inflammation, though requires frequent application 3, 6
• Sunscreen (SPF ≥15) or zinc oxide for prevention of UV-triggered recurrences 3, 7

Common Pitfalls to Avoid

• Do not rely on topical treatments alone when oral therapy is indicated - oral antivirals are significantly more effective 3, 4
• Do not delay treatment - starting after lesions fully develop dramatically reduces efficacy 4, 1
• Do not use topical antivirals for suppressive therapy - they cannot reach the site of viral reactivation 3, 4
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 4

Preventive Counseling

Counsel patients to identify and avoid personal triggers: 4

• UV light exposure (use sunscreen SPF ≥15) 3, 7
• Fever, psychological stress, menstruation 4
• Consider patient-initiated therapy where patients keep medication on hand to start at first symptoms 4