Treatment of Recurrent HSV-1 Cold Sores
For an otherwise healthy adult with typical recurrent HSV-1 cold sores, initiate oral antiviral therapy immediately at the first sign of prodrome or within 1 hour of symptom onset with either famciclovir 1500 mg as a single dose or valacyclovir 2 grams twice daily for 1 day. 1, 2, 3
First-Line Treatment Options
Single-Day Regimens (Preferred for Convenience)
- Famciclovir 1500 mg as a single dose reduces median healing time by 1.3 days compared to placebo (4.4 days vs 6.2 days) when initiated within 1 hour of symptom onset 2
- Valacyclovir 2 grams twice daily for 1 day shortens cold sore episode duration by approximately 1 day compared to placebo 3
- The 2-day valacyclovir regimen (2 grams twice daily on Day 1, then 1 gram twice daily on Day 2) offers no additional benefit over the 1-day regimen 3
Alternative Multi-Day Regimens
- Valacyclovir 500 mg twice daily for 5 days is effective for recurrent episodes when single-day therapy is not feasible 1
- Acyclovir 400 mg three times daily for 5 days or acyclovir 800 mg twice daily for 5 days are acceptable alternatives with less convenient dosing 1
- Famciclovir 125 mg twice daily for 5 days provides comparable efficacy to acyclovir regimens 1
Critical Timing Considerations
Treatment must be initiated during the prodrome or within 24 hours of lesion onset for maximum benefit, as peak viral replication occurs in the first 24 hours 1. The famciclovir single-dose regimen demonstrated efficacy when started within 1 hour of symptom onset 2. Delaying treatment beyond 72 hours significantly reduces effectiveness 1.
Suppressive Therapy for Frequent Recurrences
For patients experiencing ≥6 recurrences per year, consider daily suppressive therapy which reduces recurrence frequency by ≥75% 1:
- Valacyclovir 500 mg once daily (may be less effective with ≥10 episodes/year) 1
- Valacyclovir 250 mg twice daily 1
- Acyclovir 400 mg twice daily 1
- Famciclovir 250 mg twice daily 1
Suppressive therapy is safe for up to 6 years with acyclovir and 1 year with valacyclovir 4. After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 4.
What NOT to Do
- Never use topical acyclovir alone - it is substantially less effective than systemic treatment 5, 6, 4, 1
- Avoid delaying treatment beyond the first 24 hours of symptom onset, as efficacy diminishes rapidly 1
- Do not prescribe acyclovir 200 mg five times daily - this older regimen requires inconvenient dosing and is less effective than newer agents 1
Patient Counseling
- HSV-1 is a chronic, incurable infection with potential for lifelong recurrence 1
- Asymptomatic viral shedding can occur, though less frequently with HSV-1 than HSV-2 1
- Patients should abstain from close contact when lesions or prodromal symptoms are present 1
- Prophylactic measures like sunscreen or zinc oxide application may help reduce UV-triggered recurrences 1
- Provide a prescription for antiviral medication to self-initiate at the first sign of recurrence 1
Special Populations
For immunocompromised patients with recurrent HSV-1, higher oral doses or extended treatment duration may be required, and intravenous acyclovir should be considered for severe or disseminated disease 5, 7. Monitor for acyclovir resistance if lesions fail to respond within 7-10 days; foscarnet 40 mg/kg IV every 8 hours is the treatment for proven resistance 4.