What is the recommended treatment for a patient with cold sores, assuming no known allergies to antivirals and no immunocompromised status?

Treatment for Cold Sores (Herpes Labialis)

For immunocompetent patients with cold sores, prescribe valacyclovir 2g twice daily for 1 day, initiated at the earliest sign of symptoms (tingling, itching, or burning). 1, 2

First-Line Oral Antiviral Options

Valacyclovir is the preferred first-line treatment due to its convenient single-day dosing regimen and proven efficacy in reducing episode duration by 1.0 day compared to placebo. 1, 3 The FDA-approved regimen is 2g twice daily for 1 day (two doses taken approximately 12 hours apart). 2

Alternative oral antivirals include:

• Famciclovir 1500mg as a single dose - equally effective with single-day dosing convenience 1
• Acyclovir 400mg five times daily for 5 days - requires more frequent dosing but remains effective 1

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 Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication. 1, 4 There are no data supporting effectiveness when treatment is initiated after full lesion development. 2

Topical Treatments: Limited Role

Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy. 1, 4 Topical aciclovir 5% cream and foscarnet 3% cream have shown little to no effect in preventing or treating cold sores. 5

Supportive topical measures include:

• White soft paraffin ointment applied every 2 hours for symptomatic relief 4
• Topical anesthetics (benzydamine hydrochloride) for pain management 4

Suppressive Therapy for Frequent Recurrences

Consider daily suppressive therapy if the patient experiences six or more recurrences per year. 1

First-line suppressive 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

Daily suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent outbreaks. 1 Safety and efficacy have been documented for acyclovir for up to 6 years, while valacyclovir and famciclovir have documented safety for 1 year of continuous use. 1 After 1 year of suppressive therapy, consider discontinuation to reassess recurrence rate, as frequency often decreases over time. 1

Special Populations: Immunocompromised Patients

Immunocompromised patients may require higher doses or longer treatment durations. 1 Episodes are typically longer and more severe in this population, potentially involving the oral cavity or extending across the face. 1

For severe intraoral HSV or gingivostomatitis requiring hospitalization:

• Acyclovir 5-10 mg/kg IV every 8 hours until lesions begin to regress, then switch to oral therapy 1

Acyclovir resistance rates are significantly higher in immunocompromised patients (7%) compared to immunocompetent patients (<0.5%). 1, 6 For confirmed acyclovir-resistant HSV, foscarnet 40mg/kg IV three times daily is the treatment of choice. 1, 6

Common Pitfalls to Avoid

• Do not rely solely on topical treatments when oral therapy is significantly more effective 1, 4
• Do not start treatment after lesions have fully developed - efficacy decreases dramatically with delayed initiation 1, 2
• Do not use topical antivirals for suppressive therapy - they cannot reach the site of viral reactivation in sensory ganglia 1, 4
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could benefit substantially 1

Safety Profile

Oral antiviral medications (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events. 1 Common side effects include headache (<10%), nausea (<4%), and mild diarrhea, which are typically mild to moderate in intensity. 1 The development of resistance when using oral antivirals episodically in immunocompetent patients is rare (<0.5%). 1, 4

Patient Counseling Points

• Valacyclovir is not a cure for cold sores - it reduces episode duration and severity 2
• Maintain adequate hydration during treatment 2
• Identify and avoid personal triggers (UV light exposure, stress, fever, menstruation) 1, 4
• Use sunscreen or zinc oxide to decrease probability of recurrent outbreaks 4
• Avoid contact with lesions to prevent transmission to others 4