What is the recommended treatment for a patient presenting with cold sores?

Treatment for Cold Sores (Herpes Labialis)

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

First-Line Oral Antiviral Options

The most effective treatment approach uses short-course, high-dose oral antiviral therapy initiated within 24 hours of symptom onset:

• 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 single-day regimen 1, 2, 3
• Famciclovir 1500mg as a single dose is an equally effective alternative with single-day dosing 1, 2
• Acyclovir 400mg five times daily for 5 days remains effective but requires more frequent dosing and longer treatment duration 1, 2

Critical timing consideration: Treatment must be initiated during the prodromal phase (tingling, itching, burning) or within 24 hours of lesion onset, as peak viral titers occur in the first 24 hours and efficacy decreases significantly after lesions fully develop 1, 2, 4

Topical Treatments: Limited Role

Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy 1, 2:

• Topical penciclovir cream applied every 2 hours during waking hours for 4 days is FDA-approved but offers minimal advantage over oral therapy 5
• Topical acyclovir is even less effective than penciclovir 6
• Avoid topical corticosteroids (including acyclovir + hydrocortisone combinations), as they provide no additional benefit over acyclovir alone and carry inherent risks of aggravating infections 6

Supportive topical measures:

• White soft paraffin ointment applied every 2 hours can provide symptomatic relief 2
• Topical anesthetics (benzydamine hydrochloride) may help manage pain 2

Management of Frequent Recurrences (≥6 Episodes/Year)

For patients experiencing six or more cold sore episodes annually, daily suppressive therapy reduces recurrence frequency by ≥75% 1:

Suppressive therapy 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

Duration and monitoring:

• Safety documented for acyclovir up to 6 years; valacyclovir and famciclovir for 1 year of continuous use 1
• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence rate, as frequency decreases over time in many patients 1
• Important: Topical antivirals are completely ineffective for suppression as they cannot reach the site of viral reactivation in sensory ganglia 1

Special Populations

Immunocompromised patients:

• May require higher doses or longer treatment durations 1, 2
• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
• Higher acyclovir resistance rates (7% versus <0.5% in immunocompetent patients) 1
• For severe intraoral HSV or gingivostomatitis requiring hospitalization: acyclovir 5-10 mg/kg IV every 8 hours until lesions regress, then switch to oral therapy 1

Acyclovir-resistant HSV:

• For confirmed resistance: foscarnet 40mg/kg IV three times daily is the treatment of choice 1, 7
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative 1

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is significantly more effective 1, 2
• Starting treatment too late after lesions have fully developed, when efficacy is substantially reduced 1, 2
• Using inadequate dosing such as traditional longer courses instead of short-course, high-dose therapy 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could benefit significantly 1
• Using topical antivirals for suppression, which is completely ineffective 1

Preventive Counseling

Patients should identify and avoid personal triggers 1, 2:

• Ultraviolet light exposure (use sunscreen or zinc oxide) 1, 2
• Fever, psychological stress, menstruation 1, 2
• Provide patients with a prescription to keep on hand for immediate treatment initiation at first symptoms 1

Safety Profile

Oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1, 2:

• Common side effects: headache (<10%), nausea (<4%), diarrhea (typically mild to moderate) 1
• Development of resistance with episodic use in immunocompetent patients is rare (<0.5%) 1, 2
• Patients should maintain adequate hydration during treatment 4