What is the recommended treatment for cold sores?

Treatment for Cold Sores (Herpes Labialis)

For acute cold sore episodes, initiate valacyclovir 2g twice daily for 1 day (12 hours apart) at the earliest symptom of tingling, itching, or burning—this is the FDA-approved first-line treatment that reduces episode duration by 1.0 day compared to placebo. 1, 2

Critical Timing Considerations

• Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal phase (tingling, burning, itching) before visible lesions appear 3, 4, 1
• Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 3, 4
• Efficacy decreases significantly when treatment is initiated after lesions have fully developed (papule, vesicle, or ulcer stage) 3, 1
• Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases 3

First-Line Oral Antiviral Options

Valacyclovir (preferred):

• 2g twice daily for 1 day (doses taken 12 hours apart) 1, 2
• Reduces median episode duration by 1.0 day versus placebo 3, 2
• Offers superior convenience with single-day dosing 3, 2

Famciclovir (effective alternative):

• 1500mg as a single dose 3, 5
• Significantly reduces time to healing of primary lesions 3, 5
• Provides single-day dosing convenience 3

Acyclovir (requires more frequent dosing):

• 400mg five times daily for 5 days 3, 4
• Less convenient than valacyclovir or famciclovir due to dosing frequency 6, 3

Topical Treatments (Limited Role)

• Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy 3, 4
• Topical acyclovir 5% combined with hydrocortisone 1% (ME-609) applied 5 times daily for 5 days can prevent progression to ulcerative lesions in 42% of cases versus 26% with placebo 7
• White soft paraffin ointment applied every 2 hours can provide symptomatic relief 4
• Topical anesthetics (benzydamine hydrochloride) help manage pain 4
• Antiseptic oral rinses (1.5% hydrogen peroxide or 0.2% chlorhexidine) reduce bacterial colonization 4

Suppressive Therapy for Frequent Recurrences

Indications for suppressive therapy:

• Six or more recurrences per year 3, 4
• Particularly severe, frequent, or complicated disease 3
• Significant psychological distress from recurrences 3

Suppressive therapy regimens:

• Valacyclovir 500mg once daily (increase to 1000mg once daily for very frequent recurrences) 3, 4
• Famciclovir 250mg twice daily 3
• Acyclovir 400mg twice daily 3, 4

Efficacy and duration:

• Daily suppressive therapy reduces recurrence frequency by ≥75% 3, 4
• Safety documented for acyclovir up to 6 years; valacyclovir and famciclovir for 1 year 3
• After 1 year of continuous therapy, consider discontinuation to reassess recurrence rate, as frequency decreases over time in many patients 3

Special Populations

Immunocompromised patients:

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 3, 4
• Higher doses or longer treatment durations may be required 3, 4
• Acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 3
• For confirmed acyclovir-resistant HSV, use IV foscarnet 40mg/kg three times daily 3

Pediatric patients (≥12 years):

• Valacyclovir 2g twice daily for 1 day is FDA-approved and recommended 8, 1
• Oral antivirals are generally well-tolerated with minimal adverse events 8

Renal impairment:

• For creatinine clearance 30-49 mL/min: 1g every 12 hours (do not exceed 1 day of treatment) 1
• For creatinine clearance 10-29 mL/min: 500mg every 24 hours 1
• For creatinine clearance <10 mL/min: 500mg every 24 hours 1

Safety Profile

• Oral antivirals are generally well-tolerated with minimal adverse events 3, 4, 8
• Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate 3
• Development of resistance to oral antivirals when used episodically in immunocompetent patients is rare (<0.5%) 3, 4, 8

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is significantly more effective 3, 4, 8
• Starting treatment too late—efficacy decreases dramatically after lesions fully develop 3, 4, 8
• Using topical antivirals for suppressive therapy, which is ineffective since they cannot reach the site of viral reactivation in sensory ganglia 3, 4, 8
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could benefit from 75% reduction in frequency 3, 4
• Not counseling patients to identify and avoid personal triggers (UV light exposure, stress, fever, menstruation) 3, 4, 8
• Inadequate dosing—not using short-course, high-dose therapy which is more effective than traditional longer courses 3

Preventive Counseling

• Identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 3, 4, 8
• Use sunscreen or zinc oxide to decrease the probability of recurrent outbreaks 4
• Maintain adequate hydration during treatment 1
• Avoid contact with lesions and practice safer sex to prevent transmission 1