What is the best prescription medication for treating cold sores?

Best Prescription for Cold Sores

Valacyclovir 2g twice daily for 1 day is the best prescription medication for treating cold sores, offering the most convenient dosing with proven efficacy in reducing episode duration. 1, 2, 3

First-Line Treatment Recommendation

Valacyclovir 2g twice daily for 1 day is the optimal choice because: 1, 2

• Reduces median episode duration by 1.0 day compared to placebo with high-strength evidence 1
• Offers superior convenience with single-day dosing, improving patient adherence 1, 2
• FDA-approved specifically for cold sores in patients ≥12 years 3
• Achieves 3-5 times higher bioavailability than oral acyclovir, delivering therapeutic concentrations with less frequent dosing 4, 5

Alternative Prescription Options

If valacyclovir is not tolerated or available: 1, 2

• Famciclovir 1500mg as a single dose - equally effective alternative with convenient one-time dosing 1
• Acyclovir 400mg five times daily for 5 days - requires more frequent dosing but remains effective 1, 2

Critical Timing for Maximum Efficacy

Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (tingling, itching, burning). 1, 2

• Peak viral titers occur in the first 24 hours after lesion onset 6
• Efficacy decreases significantly when treatment starts after lesions fully develop 1, 6
• Patient-initiated therapy at first symptoms may prevent lesion development entirely in some cases 1
• The FDA label specifically notes that efficacy after clinical signs develop (papule, vesicle, ulcer) has not been established 3

When to Consider Suppressive Therapy

For patients with ≥6 recurrences per year, switch to daily suppressive therapy: 1

• Valacyclovir 500mg once daily (increase to 1000mg for very frequent recurrences) 1
• Famciclovir 250mg twice daily 1
• Acyclovir 400mg twice daily 1
• Suppressive therapy reduces recurrence frequency by ≥75% 1
• Consider discontinuation after 1 year to reassess recurrence rate 1

Common Pitfalls to Avoid

• Never rely solely on topical antivirals - they provide only modest benefit compared to oral therapy and cannot reach viral reactivation sites for suppression 1
• Don't delay treatment - waiting until lesions fully develop significantly reduces efficacy 1, 6
• Don't use inadequate dosing - short-course, high-dose therapy (valacyclovir 2g twice daily for 1 day) is more effective than traditional longer courses with lower doses 1, 2
• Don't miss suppressive therapy candidates - patients with ≥6 recurrences annually could benefit substantially 1

Safety Profile

All oral antivirals are generally well-tolerated with minimal adverse events: 1, 6

• Common side effects: headache (<10%), nausea (<4%), diarrhea (mild-moderate) 1
• Resistance development is unlikely (<0.5%) in immunocompetent patients with episodic use 1, 6
• Safe for use in pregnancy (Category B) and lactation with appropriate counseling 3