Treatment for Cold Sores (Herpes Labialis)
For acute cold sore episodes, initiate oral valacyclovir 2g twice daily for 1 day at the first sign of symptoms (prodrome or erythema stage), which reduces episode duration by approximately 1 day compared to placebo. 1, 2, 3
First-Line Oral Antiviral Therapy
Valacyclovir is the preferred first-line treatment due to its superior convenience with single-day dosing and proven efficacy:
- Valacyclovir 2g twice daily for 1 day (FDA-approved for ages ≥12 years) 1, 2, 3
- Reduces median episode duration by 1.0 day (p=0.001) 2, 4
- Shortens time to lesion healing and pain resolution 1, 4
Alternative oral regimens with comparable efficacy:
- Famciclovir 1500mg as a single dose - reduces healing time by 1.3 days compared to placebo (p=0.006) 1, 2, 5
- Acyclovir 400mg five times daily for 5 days - effective but requires more frequent dosing 1, 6
The short-course, high-dose regimens (valacyclovir and famciclovir) offer greater convenience, lower cost, and improved adherence compared to traditional 5-day acyclovir courses. 1, 2
Critical Timing for Treatment Initiation
Treatment must begin during the prodromal phase or within 24 hours of symptom onset for maximum efficacy:
- Peak viral titers occur within the first 24 hours after lesion onset 1, 6
- Efficacy decreases significantly once lesions progress beyond erythema to vesicles or ulcers 1, 6
- Patient-initiated therapy at first symptoms may prevent lesion development in some cases 1, 6
- The FDA label specifically notes that efficacy after clinical signs develop (papule, vesicle, ulcer) has not been established 3
Suppressive Therapy for Frequent Recurrences
Indications for daily suppressive therapy:
- Patients with ≥6 recurrences per year 1
- Severe, frequent, or complicated disease 1
- Significant psychological distress from recurrences 1
Suppressive therapy regimens:
- 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
Efficacy and duration:
- Reduces recurrence frequency by ≥75% 1, 6
- Acyclovir has documented safety for up to 6 years of continuous use 1, 6
- Valacyclovir and famciclovir have documented safety for 1 year 1
- After 1 year of continuous therapy, consider discontinuation to reassess recurrence frequency, as episodes often decrease over time 1, 6
Topical Treatments
Topical antivirals are NOT recommended as primary therapy because they provide only modest clinical benefit and are significantly less effective than oral therapy:
- Topical agents cannot reach the site of viral reactivation in the basal epidermis 1, 2
- They are ineffective for prophylaxis or suppression 1, 2
- Penciclovir cream reduces healing time by only 0.7 days compared to placebo 7
Special Populations
Immunocompromised patients:
- May require higher doses or longer treatment durations 1, 2
- Have higher acyclovir resistance rates (7% vs. <0.5% in immunocompetent patients) 1
- Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1
Renal impairment:
Acyclovir-resistant HSV:
- IV foscarnet 40mg/kg three times daily is the treatment of choice 1
- Resistance remains rare (<0.5%) in immunocompetent hosts 1, 2
Common Pitfalls to Avoid
- Starting treatment too late after lesions have progressed beyond erythema significantly reduces efficacy 1, 6
- Relying solely on topical treatments when oral antivirals are substantially more effective 1, 2
- Using inadequate dosing - not prescribing short-course, high-dose therapy which is more effective than traditional longer courses 1, 2
- Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
- Not counseling patients on trigger avoidance (UV light exposure, stress, fever, menstruation) to enable earlier self-initiated treatment 1, 6