Management of Fever Blisters (Herpes Simplex Labialis)
For episodic treatment of fever blisters, initiate oral valacyclovir 2g twice daily for 1 day at the first sign of symptoms (tingling, itching, burning), as this is the most effective and convenient first-line therapy. 1, 2, 3
Episodic Treatment Algorithm
First-Line Therapy
- Valacyclovir 2g twice daily for 1 day is the preferred treatment due to high bioavailability, convenient single-day dosing, and FDA approval for herpes labialis 1, 2, 3
- Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (tingling, itching, burning, pain) before lesions fully develop 1, 2
- Efficacy decreases significantly if treatment starts after lesions have fully formed 1
Alternative Oral Options
- Famciclovir 1500mg as a single dose is equally effective and FDA-approved, offering the most convenient dosing schedule 1, 4, 5
- Acyclovir 400mg five times daily for 5 days is effective but requires more frequent dosing and longer treatment duration 1, 2
- All three agents reduce outbreak duration and pain by approximately 1 day compared to placebo 2, 6
Critical Timing Considerations
- Patient-initiated therapy at first symptoms may prevent lesion development entirely in some cases 1
- The window for maximum effectiveness is narrow—treatment initiated after 24 hours shows diminished benefit 2, 3
- Patients should be counseled to keep medication on hand and start immediately when prodromal symptoms begin 1
Suppressive Therapy for Frequent Recurrences
Indications
- Six or more recurrences per year warrant consideration of daily suppressive therapy 1, 7
- Patients with severe outbreaks, complicated disease, or significant psychological distress from recurrences should also be offered suppression 1
Suppressive Regimens
- Valacyclovir 500mg once daily (can increase to 1000mg once daily for very frequent recurrences) 1
- Famciclovir 250mg twice daily 1, 4
- Acyclovir 400mg twice daily 1
- Daily suppressive therapy reduces recurrence frequency by ≥75% 1
Duration and Monitoring
- Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1, 4, 3
- Acyclovir safety is documented for up to 6 years 1
- After 1 year of suppressive therapy, discontinue treatment temporarily to reassess recurrence frequency, as many patients experience decreased recurrence rates over time 1
What NOT to Do: Common Pitfalls
Ineffective Approaches
- Do not rely on topical antivirals for suppressive therapy—they cannot reach the site of viral reactivation in nerve ganglia and provide only modest clinical benefit for episodic treatment 1, 8
- Do not use topical aciclovir, penciclovir, or foscarnet as primary therapy when oral agents are available—oral therapy is significantly more effective 1, 2, 8
- Do not delay treatment—starting therapy after lesions have fully developed substantially reduces efficacy 1, 2
Missed Opportunities
- Failing to offer suppressive therapy to patients with ≥6 recurrences per year who could significantly benefit 1, 7
- Not discussing trigger avoidance (UV light exposure, stress, fever, trauma) even while on suppressive therapy 1
Safety Profile
- Oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1
- Common side effects include headache, nausea, and diarrhea, typically mild to moderate in intensity 1
- Resistance to oral antivirals in immunocompetent patients remains extremely low (<0.5%) even with episodic use 1
- No increased risk of adverse events compared to placebo in clinical trials 1, 8
Special Considerations
Pediatric Patients
- Valacyclovir is FDA-approved for cold sores in patients ≥12 years of age 3
- Acyclovir and famciclovir dosing should be adjusted for pediatric use 4, 9
Renal Impairment
- Dose adjustments are required for all oral antivirals in patients with reduced creatinine clearance 4, 3
Pregnancy
- Further research is needed to clarify safety in pregnant women, though these agents have been used extensively 6