Antivirals for Cold Sore Outbreaks
For acute cold sore outbreaks, valacyclovir 2g twice daily for 1 day is the first-line treatment, initiated at the earliest sign of symptoms (ideally during the prodromal stage of tingling or burning). 1, 2, 3
Treatment Options for Acute Episodes
First-Line Therapy
- Valacyclovir 2g twice daily for 1 day is the preferred regimen due to its high bioavailability (3-5 times greater than acyclovir), convenient single-day dosing, and FDA approval for cold sores 1, 2, 4, 3
- This regimen reduces median episode duration by 1.0 day compared to placebo and accelerates healing time 1, 3
Alternative Oral Regimens
- Famciclovir 1500mg as a single dose is FDA-approved and highly effective, significantly reducing healing time of primary lesions 1, 4
- Acyclovir 400mg five times daily for 5 days is another option but requires more frequent dosing and is less convenient 1, 2
Critical Timing Considerations
- Treatment must be initiated within 24 hours of symptom onset for maximum effectiveness, ideally during the prodromal phase (tingling, itching, burning sensation) 1, 2
- Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 1, 5
- Efficacy decreases significantly when treatment is initiated after lesions have fully developed 1, 5
Suppressive Therapy for Frequent Recurrences
Indications
- Patients experiencing six or more recurrences per year should be offered suppressive therapy 1, 5
- Patients with particularly severe, frequent, or complicated disease warrant suppressive therapy 1
- Patients with significant psychological distress from recurrences are candidates for suppression 1
Suppressive Regimens
- Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences) 1, 5
- Famciclovir 250mg twice daily 1
- Acyclovir 400mg twice daily 1, 5
Efficacy and Duration
- Daily suppressive therapy reduces the frequency of herpes recurrences by ≥75% among patients with frequent recurrences 1, 5
- Safety and efficacy have been documented for acyclovir for up to 6 years 1
- Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1
- After 1 year of continuous suppressive therapy, consider discontinuation to assess the patient's rate of recurrent episodes, as frequency decreases over time in many patients 1
Important Clinical Considerations
What NOT to Do
- Do not rely on topical antivirals - they provide only modest clinical benefit and are substantially less effective than oral therapy 6, 1, 2
- Topical antivirals are not effective for suppressive therapy as they cannot reach the site of viral reactivation in sensory ganglia 1, 5
- Do not start treatment too late - efficacy is maximized when initiated during prodrome or within the first 24 hours 1, 5, 2
Special Populations
- Immunocompromised patients (including HIV-infected patients) may require higher doses or longer treatment durations 6, 1
- Episodes are typically longer and more severe in immunocompromised patients, potentially involving the oral cavity or extending across the face 1
- Resistance rates to acyclovir are higher in immunocompromised patients (7% vs <0.5% in immunocompetent patients) 1
- For confirmed acyclovir-resistant HSV, IV foscarnet (40mg/kg IV three times daily) is the treatment of choice 1
Safety Profile
- All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1, 5
- Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate in intensity 1
- The development of resistance to oral antiviral agents when used episodically in immunocompetent patients is unlikely (<0.5%) 1, 5