What is the initial treatment for cold sores?

Initial Treatment for Cold Sores

For cold sores (herpes labialis), initiate oral valacyclovir 2 grams twice daily for 1 day at the first sign of symptoms or lesion appearance. 1

First-Line Oral Antiviral Options

The most effective treatment approach uses high-dose, short-duration oral antiviral therapy initiated during the prodromal phase or within 24 hours of symptom onset. 1

Recommended regimens in order of preference:

• Valacyclovir 2g twice daily for 1 day - This is the preferred first-line treatment, reducing median episode duration by 1.0 day compared to placebo, with high-quality evidence supporting its efficacy. 1, 2

• Famciclovir 1500mg as a single dose - An equally effective alternative offering convenient single-day dosing with significant reduction in healing time of primary lesions. 1

• Acyclovir 400mg five times daily for 5 days - Effective but requires more frequent dosing than valacyclovir or famciclovir, making adherence more challenging. 1

Critical Timing Considerations

Treatment must begin at the earliest symptoms (tingling, burning, itching) or within 24 hours of lesion onset for optimal efficacy. 1 Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication and preventing full lesion development. 1 Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases. 1

Why Oral Therapy Over Topical

Oral antivirals are substantially more effective than topical treatments. 1 Topical antivirals provide only modest clinical benefit and cannot reach the site of viral reactivation in nerve ganglia where the virus resides. 1 The superior bioavailability of oral valacyclovir (3-5 times greater than oral acyclovir) allows for less frequent dosing while achieving therapeutic concentrations. 2, 3

Special Populations Requiring Modified Treatment

Immunocompromised patients may require higher doses or longer treatment durations. 1 For these patients, consider:

• Acyclovir 400mg orally 3-5 times daily until clinical resolution 4
• Severe cases require IV acyclovir 5mg/kg every 8 hours 4
• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
• Acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 1, 4

Patients with renal impairment require dose adjustments based on creatinine clearance to prevent acute renal failure. 5, 4

When to Consider Suppressive Therapy

For patients experiencing 6 or more recurrences per year, daily suppressive therapy should be considered. 1 Options include:

• 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 recurrences. 1 After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency, as it decreases over time in many patients. 1

Treatment Failure and Resistance

If lesions do not begin to resolve within 7-10 days after initiating appropriate antiviral therapy, suspect acyclovir resistance. 4 For confirmed acyclovir-resistant HSV (rare at <0.5% in immunocompetent hosts but up to 7% in immunocompromised patients), IV foscarnet 40mg/kg every 8 hours until complete clinical resolution is the treatment of choice. 1, 4 All acyclovir-resistant strains are also resistant to valacyclovir and most are resistant to famciclovir. 4

Common Pitfalls to Avoid

• Starting treatment too late - Efficacy decreases significantly when treatment is initiated after lesions have fully developed. 1
• Using inadequate dosing - The genital herpes regimen (valacyclovir 500mg twice daily for 5-10 days) is different from the orolabial regimen (2g twice daily for 1 day). 4
• Relying solely on topical treatments - These are substantially less effective than oral therapy and cannot reach the site of viral reactivation. 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit. 1

Safety Profile

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 in intensity. 1 Despite increasing use, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts). 1

Preventive Counseling

Patients should identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation. 1 Even while on suppressive therapy, trigger avoidance remains important as suppressive therapy reduces but does not eliminate asymptomatic viral shedding. 1