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

Treatment for Cold Sores (Herpes Labialis)

For episodic treatment of cold sores, initiate oral valacyclovir 2g twice daily for 1 day at the first sign of symptoms (prodrome), which reduces episode duration by approximately 1 day compared to placebo. 1, 2, 3

First-Line Episodic Treatment Options

Oral antiviral therapy is superior to topical treatments and should be the standard approach. 4, 1, 2

Preferred Regimen

• Valacyclovir 2g twice daily for 1 day is the most convenient and effective first-line option, FDA-approved for cold sores in adults and children ≥12 years 5, 3
• This high-dose, short-duration regimen reduces median episode duration by 1.0 day (p=0.001) and mean duration by 1.1 days compared to placebo 3
• Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal phase (tingling, burning, itching) before visible lesions appear 4, 2

Alternative Oral Regimens

• Famciclovir 1500mg as a single dose is equally effective, significantly reducing healing time and offering maximum convenience 1, 2, 6
• Acyclovir 400mg five times daily for 5 days is effective but requires more frequent dosing, making adherence more challenging 1, 2

Topical Treatments: Limited Role

Topical antivirals provide only modest clinical benefit and are significantly less effective than oral therapy. 7, 1

• Topical penciclovir cream is FDA-approved but offers minimal advantage over placebo 8
• Topical aciclovir 5% cream has limited efficacy for episodic treatment 9, 10
• The combination of aciclovir + hydrocortisone cream shows no significant benefit over aciclovir alone and adds unnecessary corticosteroid exposure 9

Suppressive Therapy for Frequent Recurrences

Patients with ≥6 recurrences per year should be offered daily suppressive therapy, which reduces recurrence frequency by ≥75%. 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

Duration and Monitoring

• Safety and efficacy documented for acyclovir up to 6 years of continuous use 1
• Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1
• After 1 year of suppressive therapy, consider a trial off medication to reassess recurrence frequency, as it naturally decreases over time in many patients 1

Critical Timing Considerations

The window for effective treatment is narrow—therapy must begin within the first 24 hours of symptom onset. 4, 2

• Peak viral titers occur in the first 24 hours after lesion onset, when most lesions are vesicular 4
• Natural healing begins within 24 hours, making early intervention essential 4
• Efficacy of valacyclovir initiated after visible lesion development (papule, vesicle, ulcer) has not been established 5
• Patient-initiated therapy at first prodromal symptoms may prevent lesion development entirely in some cases 1

Safety Profile

All oral antivirals (acyclovir, valacyclovir, famciclovir) are well-tolerated with minimal adverse events. 1

• Common side effects include headache (<10%), nausea (<4%), and diarrhea, typically mild to moderate in severity 1
• Resistance to oral antivirals remains rare (<0.5%) in immunocompetent patients, even with episodic use 1
• In immunocompromised patients, resistance rates increase to approximately 7% 1

Adjunctive Measures

• Sunscreen or zinc oxide application may help prevent UV-triggered recurrences 4
• Patients should be counseled on avoiding known triggers (UV light, fever, stress, menstruation) 4

Common Pitfalls to Avoid

• Do not rely on topical treatments when oral therapy is indicated—oral antivirals are significantly more effective 1, 2
• Do not delay treatment initiation—efficacy decreases dramatically when treatment starts after lesions fully develop 4, 2
• Do not use inadequate dosing—short-course, high-dose therapy (valacyclovir 2g BID x1 day) is more effective than traditional longer courses with lower doses 1, 2, 3
• Do not overlook candidates for suppressive therapy—patients with ≥6 recurrences per year experience significant quality of life improvement with daily suppression 1
• Do not prescribe topical antivirals for suppression—they cannot reach the site of viral reactivation in sensory ganglia 1

Special Populations

• For immunocompromised patients, episodes are typically longer and more severe, potentially requiring higher doses or longer treatment duration 4
• For acyclovir-resistant HSV infection (rare in immunocompetent hosts), foscarnet 40mg/kg IV three times daily is recommended 1
• Valacyclovir is FDA-approved for cold sores in pediatric patients ≥12 years of age 5