What is the recommended prescription therapy for a patient presenting with cold sores (herpes simplex labialis)?

Prescription Therapy for Cold Sores

For cold sores (herpes labialis), prescribe valacyclovir 2 grams twice daily for 1 day (12 hours apart), initiated at the earliest symptom such as tingling, itching, or burning. 1

First-Line Treatment Options

Valacyclovir is the preferred first-line agent due to its superior convenience and proven efficacy:

• Valacyclovir 2g twice daily for 1 day (doses taken 12 hours apart) reduces median episode duration by 1.0 day compared to placebo (p=0.001) and is FDA-approved for this indication 2, 1, 3
• This single-day regimen offers the most convenient dosing schedule, which improves patient adherence 2, 4
• Valacyclovir has 3-5 times better bioavailability than acyclovir, allowing for less frequent dosing 3, 5

Alternative oral antivirals if valacyclovir is unavailable:

• Famciclovir 1500mg as a single dose significantly reduces healing time of primary lesions 2, 4
• Acyclovir 400mg five times daily for 5 days remains effective but requires more frequent dosing 2, 4

Critical Timing Considerations

Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset for optimal therapeutic benefit, as peak viral titers occur in the first 24 hours after lesion onset 2, 4. Efficacy decreases significantly when treatment begins after lesions have fully developed 2, 1.

Provide patients with a prescription to keep on hand so they can initiate therapy immediately at first symptoms (tingling, itching, burning) without delay 2.

Suppressive Therapy for Frequent Recurrences

For patients with 6 or more recurrences per year, consider daily suppressive therapy 2:

• Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences) 2
• Famciclovir 250mg twice daily 2
• Acyclovir 400mg twice daily 2

Suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent outbreaks 2. Safety and efficacy are documented for acyclovir up to 6 years and for valacyclovir/famciclovir up to 1 year of continuous use 2. After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients 2.

Important Clinical Pitfalls to Avoid

• Do not rely on topical antivirals as primary therapy - they provide only modest clinical benefit and are substantially less effective than oral therapy 2, 4
• Topical antivirals cannot be used for suppression as they cannot reach the site of viral reactivation 2
• Do not delay treatment - starting therapy after lesions have fully developed significantly reduces efficacy 2
• Do not use inadequate dosing - short-course, high-dose therapy (valacyclovir 2g twice daily for 1 day) is more effective than traditional longer courses with lower doses 2, 4

Special Populations

Immunocompromised patients may require higher doses or longer treatment durations, with acyclovir resistance rates of 7% versus <0.5% in immunocompetent patients 2. Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 2.

For acyclovir-resistant HSV infection (confirmed by viral culture with susceptibility testing), foscarnet 40mg/kg IV three times daily is the treatment of choice 2.

Renal impairment requires dose adjustments based on creatinine clearance for all oral antivirals 2.

Safety Profile

All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 2. Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate in intensity 2. Despite increasing use, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts) 2.

Preventive Counseling

Counsel patients to identify and avoid personal triggers including ultraviolet light exposure (recommend sunscreen or zinc oxide), fever, psychological stress, and menstruation 2, 4.