What is the recommended treatment for a patient with fever blisters (cold sores) on the lips?

Treatment of Fever Blisters (Cold Sores) on the Lips

For cold sores on the lips, initiate oral valacyclovir 2g twice daily for 1 day at the first sign of symptoms (prodrome or within 24 hours of lesion onset) as first-line therapy. 1, 2

First-Line Oral Antiviral Options

The most effective treatment approach uses short-course, high-dose oral antiviral therapy initiated as early as possible:

• Valacyclovir 2g twice daily for 1 day is the preferred first-line treatment, reducing episode duration by 1.0 day compared to placebo and offering the most convenient single-day dosing regimen 1, 2, 3

• Famciclovir 1500mg as a single dose is an equally effective alternative with single-day dosing, significantly reducing healing time of primary lesions 1, 2

• Acyclovir 400mg five times daily for 5 days is another option but requires more frequent dosing and is less convenient than valacyclovir or famciclovir 1

Critical Timing Considerations

Treatment must be initiated during the prodromal phase (tingling, burning sensation) or within 24 hours of lesion onset to achieve optimal benefit, as peak viral titers occur in the first 24 hours after lesion development 1, 2. Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases 1.

Topical Treatment Options (Less Effective)

While available, topical treatments are significantly less effective than oral therapy:

• Docosanol 10% cream (over-the-counter) can be applied 5 times daily at the first sign of cold sore, but provides only modest clinical benefit compared to oral antivirals 4

• Topical antivirals are not effective for suppressive therapy as they cannot reach the site of viral reactivation in sensory nerve ganglia 1, 2

Suppressive Therapy for Frequent Recurrences

For patients experiencing 6 or more recurrences per year, initiate daily suppressive therapy with one of the following options 1:

• 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 recurrences 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 the patient's recurrence rate, as frequency decreases over time in many patients 1, 5.

Special Populations and Considerations

Immunocompromised patients typically experience more prolonged and severe episodes that may involve the oral cavity or spread across the face 1. These patients may require:

• Higher doses or longer treatment durations 1, 2
• Awareness that acyclovir resistance rates are higher (7% versus <0.5% in immunocompetent patients) 1, 6

For acyclovir-resistant HSV (confirmed by susceptibility testing), IV foscarnet 40mg/kg three times daily is the treatment of choice 1, 6.

Renal impairment requires dose adjustments based on creatinine clearance for acyclovir and valacyclovir 1.

Safety Profile

All oral antivirals (acyclovir, valacyclovir, famciclovir) are generally well-tolerated with minimal adverse events 1, 7:

• Headache occurs in <10% of patients 7
• Nausea occurs in <4% of patients 7
• Diarrhea and mild gastrointestinal disturbances are typically mild to moderate in intensity 1, 7

Despite increasing use of HSV-specific antiviral agents, the incidence of resistant HSV-1 strains remains low (<0.5% in immunocompetent hosts) 1, 2.

Preventive Counseling

Counsel patients to identify and avoid personal triggers 1:

• UV light exposure: Apply sunscreen or zinc oxide to decrease UV light-triggered recurrences 1
• Fever, psychological stress, and menstruation 1

Common Pitfalls to Avoid

• Relying solely on topical treatments when oral therapy is significantly more effective 1, 2
• Starting treatment too late: Efficacy decreases significantly when treatment is initiated after lesions have fully developed 1
• Inadequate dosing: Not using short-course, high-dose therapy, which is more effective than traditional longer courses 1, 2
• Failing to consider suppressive therapy in patients with frequent recurrences (≥6 per year) who could significantly benefit 1