What is the first‑line treatment for herpes labialis in a typical adult with a first episode or recurrent outbreak?

First-Line Treatment for Herpes Labialis

For a typical adult with either first episode or recurrent herpes labialis, initiate oral valacyclovir 2 grams twice daily for 1 day (two doses 12 hours apart) at the earliest sign of symptoms—this is the CDC-recommended first-line therapy with the highest strength of evidence. 1

Treatment Algorithm

Timing Is Critical

• Start therapy during the prodromal phase (tingling, itching, burning, pain) or within 24 hours of lesion onset to achieve maximum benefit, as peak viral titers occur in the first 24 hours after lesion appearance 1
• Efficacy decreases significantly when treatment begins after the first 24 hours, resulting in longer lesion duration and reduced symptom relief 1
• Patient-initiated therapy at first symptoms may even prevent lesion development in some cases 1

First-Line Oral Antiviral Options (in order of preference)

Option 1: Valacyclovir (preferred)

• 2 grams twice daily for 1 day (12 hours apart) 1
• Reduces median episode duration by 1.0 day compared to placebo 1
• Superior bioavailability and more convenient dosing than acyclovir 1
• High strength of evidence 1

Option 2: Famciclovir (equally effective alternative)

• 1500 mg as a single dose 1, 2
• Significantly reduces healing time of primary lesions 1
• Single-dose convenience may improve adherence 1, 3
• Moderate strength of evidence 1

Option 3: Acyclovir (effective but less convenient)

• 400 mg five times daily for 5 days 1, 4
• Requires more frequent dosing, which may reduce patient compliance 1
• Less expensive but inferior bioavailability compared to valacyclovir and famciclovir 1, 5
• High strength of evidence 1

Important Clinical Considerations

What NOT to Use

• Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy—they should not be relied upon as primary treatment 1, 5
• Topical agents cannot reach the site of viral reactivation and are ineffective for suppressive therapy 1

When to Consider Suppressive Therapy

• Patients with ≥6 recurrences per year should be offered daily suppressive therapy 1
• Suppressive options include:
  • Valacyclovir 500 mg once daily (can increase to 1000 mg for very frequent recurrences) 1
  • Famciclovir 250 mg twice daily 1, 2
  • Acyclovir 400 mg twice daily 1
• Daily suppressive therapy reduces recurrence frequency by ≥75% 1

Special Populations

• Immunocompromised patients experience longer, more severe episodes that may involve the oral cavity or extend across the face 1
• These patients may require higher doses or longer treatment durations 1
• Acyclovir resistance rates are higher in immunocompromised patients (7% versus <0.5% in immunocompetent hosts) 1
• For confirmed acyclovir-resistant HSV, use foscarnet 40 mg/kg IV three times daily 1

Common Pitfalls to Avoid

• Starting treatment too late: Initiating therapy after lesions have fully developed significantly reduces efficacy 1
• Relying on topical treatments: Oral antivirals are superior and should be the standard of care 1
• Inadequate dosing: Using traditional longer courses instead of short-course, high-dose therapy, which is more effective and improves adherence 1
• Failing to provide a prescription for patient-initiated therapy: Give patients a prescription to keep on hand so treatment can begin immediately at first symptoms 1

Preventive Counseling

• Counsel patients to identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 1
• Applying sunscreen (SPF 15 or higher) or zinc oxide can decrease the probability of UV light-triggered recurrences 1, 4
• Patients remain contagious until all lesions are fully crusted and should avoid direct contact (kissing) and sharing items that contact the mouth during active outbreaks 1

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
• Development of resistance with episodic use in immunocompetent patients is unlikely (<0.5%) 1