What is the recommended treatment for cold sores (herpes simplex labialis)?

Cold Sore Treatment

For episodic treatment of cold sores, initiate valacyclovir 2g twice daily for 1 day (two doses 12 hours apart) at the first sign of prodromal symptoms (tingling, itching, or burning), as this provides the most convenient and effective oral antiviral regimen. 1, 2, 3

First-Line Episodic Treatment Options

Oral antivirals are significantly more effective than topical therapies and should be the standard of care. 4, 1

Preferred Regimens (in order of convenience):

• Valacyclovir 2g twice daily for 1 day (two doses 12 hours apart) - reduces episode duration by 1.0 day compared to placebo 1, 3
• Famciclovir 1500mg as a single dose - significantly reduces healing time of primary lesions 4, 1
• Acyclovir 400mg five times daily for 5 days - effective but requires more frequent dosing and is less convenient 4

The short-course, high-dose regimens (valacyclovir and famciclovir) offer superior convenience, improved adherence, and cost-effectiveness compared to traditional longer courses. 4, 1

Critical Timing Considerations

Treatment must be initiated during the prodromal phase (tingling, itching, burning) or within 24 hours of lesion onset for optimal efficacy. 4, 1

• Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 1
• Efficacy of treatment initiated after visible lesions develop (papule, vesicle, ulcer) has not been established 2
• The natural healing process begins within 24 hours, so delayed treatment provides minimal benefit 4

Patients should be counseled to keep medication on hand and self-initiate treatment immediately at first symptoms. 1, 2

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year, initiate daily suppressive therapy rather than relying solely on episodic treatment. 1

Suppressive Regimen 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

Key Points About Suppressive Therapy:

• Reduces recurrence frequency by ≥75% in patients with frequent outbreaks 1
• Safety documented for acyclovir up to 6 years; valacyclovir and famciclovir for 1 year 1
• After 1 year of continuous therapy, consider discontinuation to reassess recurrence rate, as frequency naturally decreases over time in many patients 1
• Topical antivirals are completely ineffective for suppression as they cannot reach the site of viral reactivation in the sensory ganglia 4, 1

Why Topical Therapies Are Inferior

Topical antivirals (including acyclovir cream) provide only modest clinical benefit and should not be first-line therapy. 4, 1

• Topical agents reduce healing time by only 0.5 days compared to oral therapies that reduce it by 1+ days 4
• Poor skin penetration limits efficacy 5, 6
• Require frequent application (5-6 times daily) with lower adherence 4
• Do not impact the host immune response or inflammatory cascade 4

Special Populations

Immunocompromised Patients:

• Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 4, 1
• Higher doses or longer treatment durations may be required 1
• Resistance rates to acyclovir are higher (7% vs <0.5% in immunocompetent hosts) 1

Pediatric Patients:

• Valacyclovir is FDA-approved for cold sores in patients ≥12 years old 2
• Initiate treatment at earliest symptoms, not after visible lesions develop 2

Preventive Counseling

Patients should identify and avoid personal triggers to reduce recurrence frequency: 4, 1

• Ultraviolet light exposure (use sunscreen or zinc oxide on lips)
• Fever
• Psychological stress
• Menstruation

Common Pitfalls to Avoid

• Relying on topical treatments when oral therapy is more effective - topical agents are substantially inferior 4, 1
• Starting treatment too late - efficacy decreases dramatically after lesions fully develop 4, 1
• Not prescribing suppressive therapy for patients with ≥6 recurrences per year who could significantly benefit 1
• Using inadequate dosing - short-course, high-dose therapy is more effective than traditional longer courses 4, 1
• Failing to educate patients about keeping medication on hand for immediate self-initiation at first symptoms 1, 2

Safety Profile

All 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 1
• Development of resistance with episodic use in immunocompetent patients is rare (<0.5%) 1
• Patients should maintain adequate hydration during treatment 2

Patient Education Points

• Valacyclovir is not a cure for cold sores - it reduces symptom duration and accelerates healing 2
• Treatment for cold sores should not exceed 1 day (2 doses taken 12 hours apart) for the valacyclovir regimen 2
• Cold sores are contagious - avoid contact with lesions and sharing items that touch the mouth 2
• If a dose is missed, take it as soon as remembered, but do not double the next dose 2