Valtrex (Valacyclovir) for Cold Sores
For cold sores, take valacyclovir 2 grams twice daily for 1 day (two doses separated by 12 hours), starting at the very first sign of symptoms like tingling, itching, or burning. 1
Treatment Regimen
Episodic Treatment (First-Line)
- Valacyclovir 2g twice daily for 1 day is the FDA-approved regimen for cold sores 1
- Take the two doses exactly 12 hours apart 1
- This single-day, high-dose regimen reduces episode duration by approximately 1 day compared to placebo and is more convenient than traditional multi-day courses 2
Alternative Episodic Options
- Famciclovir 1500mg as a single dose is equally effective 3
- Acyclovir 400mg five times daily for 5 days (requires more frequent dosing but remains effective) 4, 3
Critical Timing Considerations
Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset for optimal efficacy 3, 5. Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 3. Patient-initiated therapy at first symptoms may even prevent lesion development in some cases 3.
Keep medication on hand so you can start treatment immediately when symptoms begin—waiting even a few hours significantly reduces effectiveness 3.
Suppressive Therapy for Frequent Recurrences
If you experience 6 or more cold sore outbreaks per year, consider daily suppressive therapy 3:
- Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences ≥10 per year) 4, 3
- Alternative: Famciclovir 250mg twice daily 3
- Alternative: Acyclovir 400mg twice daily 3
Suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent outbreaks 4, 3. Safety and efficacy have been documented for acyclovir up to 6 years and for valacyclovir/famciclovir up to 1 year of continuous use 4, 3. After 1 year of continuous suppressive therapy, discuss discontinuation with your provider to reassess recurrence frequency, as it often decreases over time 4, 3.
Important Clinical Considerations
Oral antivirals are vastly superior to topical treatments—topical antivirals provide only modest clinical benefit and cannot reach the site of viral reactivation in nerve ganglia 3. Do not rely on topical treatments when oral therapy is indicated 3.
Valacyclovir is generally well-tolerated with minimal adverse events; the most common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate 3, 5.
Resistance to valacyclovir remains extremely low (<0.5%) in immunocompetent patients 3. Despite increasing use of HSV-specific antiviral agents, clinically significant resistance is unlikely to develop with episodic use 3.
Special Populations
Immunocompromised patients may require higher doses or longer treatment durations, and have higher acyclovir resistance rates (7% versus <0.5% in immunocompetent patients) 3, 5. Episodes are typically longer and more severe in this population, potentially involving the oral cavity or extending across the face 3.
Renal impairment requires dose adjustments to prevent acute renal failure 3, 1.
Preventive Counseling
Identify and avoid personal triggers including ultraviolet light exposure, fever, psychological stress, and menstruation 3. Applying sunscreen or zinc oxide can decrease the probability of UV light-triggered recurrences 3.
Common Pitfalls to Avoid
- Starting treatment too late—efficacy decreases significantly when treatment is initiated after lesions have fully developed 3
- Relying solely on topical treatments when oral therapy is more effective 3
- Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 3
- Not discussing potential triggers that patients should avoid even while on suppressive therapy 3