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

Treatment of Fever Blisters (Herpes Simplex Labialis)

For fever blisters, initiate oral valacyclovir 2 grams twice daily for 1 day (two doses taken 12 hours apart) at the earliest symptom of tingling, itching, or burning—this is the only FDA-approved single-day treatment and reduces healing time by approximately 1 day compared to placebo. 1, 2

First-Line Treatment Options

Acute Episode Treatment (Start at Prodrome)

• Valacyclovir 2g twice daily for 1 day is the preferred first-line treatment, offering the most convenient dosing schedule with high efficacy when initiated during the prodromal phase 1, 2
• Famciclovir 1500mg as a single dose is an equally effective alternative with single-day dosing 1
• Acyclovir 400mg five times daily for 5 days remains effective but requires more frequent dosing and is less convenient 1

Critical Timing Considerations

• Treatment must be initiated at the earliest symptom (tingling, itching, burning) during the prodromal phase 1, 2
• Efficacy has not been established once clinical lesions have developed (papule, vesicle, or ulcer stage) 2
• Peak viral titers occur within the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 1
• Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases 1

Suppressive Therapy for Frequent Recurrences

For patients with 6 or more recurrences per year, initiate daily suppressive therapy with valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences). 1

Indications for Suppressive Therapy

• Six or more recurrences per year 1
• Particularly severe, frequent, or complicated disease 1
• Significant psychological distress from recurrences 1

Suppressive Therapy Options

• Valacyclovir 500mg once daily (increase to 1000mg once daily if needed) 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 1
• Valacyclovir and famciclovir have documented safety 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

Important Clinical Considerations

What NOT to Do

• Do not rely on topical antivirals—they provide only modest clinical benefit, are substantially less effective than oral therapy, and cannot reach the site of viral reactivation for suppressive therapy 1, 3
• Do not start treatment after lesions have fully developed—efficacy decreases significantly 1
• Do not use inadequate dosing regimens (e.g., traditional longer courses at lower doses are less effective than short-course, high-dose therapy) 1

Safety Profile

• All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1, 4
• Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate in intensity 1, 4
• Despite increasing use of HSV-specific antiviral agents, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts) 1

Patient Counseling

• Valacyclovir is not a cure for cold sores—it only treats active episodes and reduces recurrence frequency 2
• Patients should identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 1
• Maintain adequate hydration during treatment 2
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 1

Special Populations

Immunocompromised Patients

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
• Higher doses or longer treatment durations may be required 1
• Acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 1
• For severe intraoral HSV or gingivostomatitis requiring hospitalization: acyclovir 5-10mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy 1

Acyclovir-Resistant HSV

• For confirmed acyclovir-resistant HSV infection, foscarnet 40mg/kg IV three times daily is the treatment of choice 1