What is the treatment for a cold sore?

Treatment for Cold Sores (Herpes Labialis)

Oral valacyclovir 2g twice daily for 1 day is the first-line treatment for cold sores, initiated at the earliest sign of symptoms (tingling, itching, or burning), which reduces episode duration by approximately 1 day compared to placebo. 1, 2, 3

First-Line Oral Antiviral Therapy

Treatment must be initiated within 24 hours of symptom onset—ideally during the prodromal stage—because peak viral titers occur in the first 24 hours after lesion onset. 1, 2 Starting treatment after lesions fully develop significantly reduces efficacy. 1

Recommended Oral Regimens (in order of preference):

• Valacyclovir 2g twice daily for 1 day - Most convenient dosing with high bioavailability 1, 2, 4, 3
• Famciclovir 1500mg as a single dose - Effective alternative with single-day dosing 1, 2, 5
• Acyclovir 400mg five times daily for 5 days - Requires more frequent dosing but effective 1, 2, 4

Short-course, high-dose regimens (valacyclovir and famciclovir) offer superior convenience and may improve adherence compared to traditional longer courses. 1, 4

Topical Treatments (Limited Role)

Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy. 1, 2 They cannot reach the site of viral reactivation in sensory ganglia and should not be relied upon as primary treatment. 1

Supportive topical measures include:

• White soft paraffin ointment applied every 2 hours for symptom relief 2
• Topical anesthetics (benzydamine hydrochloride) for pain management 2
• Antiseptic oral rinses (1.5% hydrogen peroxide or 0.2% chlorhexidine) to reduce bacterial colonization 2

Penciclovir cream 1% applied every 2 hours while awake for 4 days is FDA-approved but offers minimal benefit over oral therapy. 6

Suppressive Therapy for Frequent Recurrences

Patients experiencing 6 or more recurrences per year should be offered daily suppressive therapy, which reduces recurrence frequency by ≥75%. 1, 2

Suppressive Regimen Options:

• Valacyclovir 500mg once daily (can increase to 1000mg daily for very frequent recurrences) 1
• Famciclovir 250mg twice daily 1
• Acyclovir 400mg twice daily 1

After 1 year of continuous suppressive therapy, consider a trial off medication to reassess recurrence frequency, as it naturally decreases over time in many patients. 1 Safety has been documented for acyclovir up to 6 years and for valacyclovir/famciclovir for 1 year of continuous use. 1

Special Populations

Immunocompromised patients may require higher doses or longer treatment durations, as episodes are typically more severe and prolonged. 1, 2 Acyclovir resistance rates are higher in this population (7% vs. <0.5% in immunocompetent patients). 1 For confirmed acyclovir-resistant HSV, IV foscarnet 40mg/kg three times daily is the treatment of choice. 1

Valacyclovir is FDA-approved for cold sores in patients ≥12 years of age. 7 For pregnant or breastfeeding women, acyclovir (the active metabolite of valacyclovir) is present in breast milk at levels providing approximately 0.6 mg/kg/day to the infant. 7

Common Pitfalls to Avoid

• Starting treatment too late - Efficacy drops dramatically after the first 24 hours 1, 2
• Relying solely on topical treatments when oral therapy is far more effective 1, 2
• Using topical antivirals for suppression - They cannot reach viral reservoirs in ganglia 1, 2
• Failing to offer suppressive therapy to patients with ≥6 recurrences annually who could benefit substantially 1, 2
• Inadequate dosing - Not using short-course, high-dose regimens that improve adherence 1, 4

Preventive Counseling

Patients should identify and avoid personal triggers including:

• Ultraviolet light exposure (use sunscreen or zinc oxide) 1, 2
• Fever and psychological stress 1, 2
• Menstruation 1

Safety Profile

Oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events. 1, 2 Common side effects include headache (<10%), nausea (<4%), and mild diarrhea, which are typically mild to moderate in intensity. 1 Resistance development with episodic use in immunocompetent patients remains rare (<0.5%). 1, 2