What is the recommended treatment for a typical fever blister (herpes labialis), including first‑line topical and oral antiviral options, dosing, and indications for suppressive therapy?

Treatment of Fever Blisters (Herpes Labialis)

For episodic treatment of fever blisters, oral valacyclovir 2g twice daily for 1 day is the first-line therapy, initiated at the earliest sign of prodromal symptoms or within 24 hours of lesion onset. 1

First-Line Oral Antiviral Options

Oral antivirals are superior to topical therapies and should be the standard of care for patients seeking treatment 1, 2:

• Valacyclovir 2g twice daily for 1 day – Most convenient single-day regimen, reduces median episode duration by 1.0 day compared to placebo 1
• Famciclovir 1500mg as a single dose – Equally effective alternative with single-dose convenience, significantly reduces healing time of primary lesions 1, 3
• Acyclovir 400mg five times daily for 5 days – Effective but requires more frequent dosing and lower compliance 1, 2

The short-course, high-dose regimens (valacyclovir and famciclovir) offer greater convenience, cost-effectiveness, and improved adherence compared to traditional 5-7 day therapy 4, 3.

Critical Timing for Treatment Initiation

Treatment must be started during the prodromal phase (tingling, burning, itching) or within 24 hours of lesion onset to achieve optimal benefit 5, 1. Peak viral titers occur in the first 24 hours after lesion onset, making early intervention essential for blocking viral replication 5. Efficacy decreases significantly when treatment is initiated after lesions have fully developed 1.

Provide patients with a prescription to keep on hand so treatment can be initiated immediately at first symptoms 1.

Topical Antiviral Therapy (Second-Line)

Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy 1, 2:

• 5% acyclovir cream – May reduce lesion duration if applied early and frequently (every 2 hours during waking hours), but inferior to oral therapy 6, 7
• 1% penciclovir cream – Superior to topical acyclovir but still less effective than oral antivirals 7
• Docosanol 10% – Over-the-counter option with limited evidence 4

Topical therapies are not effective for suppressive therapy as they cannot reach the site of viral reactivation in sensory ganglia 1.

Indications for Suppressive Therapy

Consider daily suppressive therapy for patients with 1, 2:

• Six or more recurrences per year (primary indication)
• Particularly severe, frequent, or complicated disease
• Significant psychological distress from recurrences

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

Daily suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent outbreaks 1. Safety and efficacy have been documented for acyclovir for up to 6 years, and for valacyclovir and famciclovir for 1 year of continuous use 1. After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence rate, as frequency decreases over time in many patients 1.

Preventive Measures

Counsel patients to identify and avoid personal triggers 5, 1:

• UV light exposure – Apply sunscreen (SPF 15 or above) or zinc oxide to lips before sun exposure 5, 6
• Fever, psychological stress, menstruation 5

Sunscreen alone can effectively prevent UV-triggered recurrences 6.

Special Populations

Immunocompromised Patients

Episodes are typically longer and more severe in immunocompromised patients, potentially involving the oral cavity or extending across the face 5, 1. These patients may require higher doses or longer treatment durations 1. Acyclovir resistance rates are higher in immunocompromised patients (7% vs <0.5% in immunocompetent hosts) 5, 1.

For confirmed acyclovir-resistant HSV, foscarnet 40mg/kg IV three times daily is the treatment of choice 1.

Severe Intraoral HSV or Gingivostomatitis

• Mild cases: Acyclovir 20mg/kg (maximum 400mg/dose) orally three times daily for 5-10 days 1
• Moderate to severe cases requiring hospitalization: Acyclovir 5-10mg/kg IV three times daily until lesions begin to regress, then switch to oral therapy until complete healing 1

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is more effective 1
• Starting treatment too late – efficacy decreases significantly after the first 24 hours 5, 1
• Failing to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
• Not discussing trigger avoidance (UV light, stress, fever) even while on suppressive therapy 1

Safety Profile

All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1. Common side effects include headache (<10%), nausea (<4%), and diarrhea, which are typically mild to moderate 1. Despite increasing use, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts) 5, 1.

Contagiousness and Transmission Prevention

Patients remain contagious until all lesions are fully crusted 1. Even with optimal antiviral therapy, viral shedding persists for approximately 6.4 days with valacyclovir (compared to 8.1 days with placebo) 1. Advise patients to avoid direct contact (kissing, sharing utensils, towels, lip balm) until all lesions have completely crusted 1.