What is the treatment for oral herpes simplex?

Treatment of Oral Herpes Simplex (Cold Sores)

For oral herpes simplex (cold sores), initiate oral valacyclovir 2g twice daily for 1 day at the earliest sign of symptoms, which is the most effective first-line treatment. 1, 2, 3

First-Line Treatment Options

Episodic Treatment for Acute Outbreaks

Valacyclovir is the preferred agent due to its superior convenience and proven efficacy:

• Valacyclovir 2g twice daily for 1 day (single-day therapy) reduces median episode duration by 1.0 day compared to placebo and offers the most convenient dosing 1, 3
• Alternative: Valacyclovir 500mg twice daily for 5-7 days for mild to moderate infections 2

Famciclovir is an equally effective alternative:

• Famciclovir 1500mg as a single dose significantly reduces healing time with comparable efficacy to valacyclovir 1, 3
• Alternative: Famciclovir 250mg twice daily for 5-7 days 2

Acyclovir remains a viable option but requires more frequent dosing:

• Acyclovir 400mg orally three times daily for 5-7 days 2
• Acyclovir 400mg five times daily for 5 days (older regimen) 4, 5

Critical Timing Considerations

Treatment must be initiated during the prodromal phase or within 24 hours of symptom onset for maximum efficacy, as peak viral titers occur in the first 24 hours after lesion onset 1, 3. Patient-initiated episodic therapy at first symptoms may even prevent lesion development in some cases 1. Efficacy decreases significantly when treatment is initiated after lesions have fully developed 1.

Suppressive Therapy for Frequent Recurrences

Patients with ≥6 recurrences per year should receive daily suppressive therapy, which reduces recurrence frequency by ≥75% 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, 4

Duration and Monitoring of Suppressive Therapy

• Acyclovir has documented safety for up to 6 years of continuous use 1
• Valacyclovir and famciclovir have documented safety for 1 year of continuous use 1
• After 1 year of suppressive therapy, discontinue treatment to reassess recurrence rate, as frequency decreases over time in many patients 1

Additional Indications for Suppressive Therapy

Beyond frequency thresholds, consider suppressive therapy for:

• Particularly severe or complicated disease 1
• Significant psychological distress from recurrences 1

Topical Treatments: Limited Role

Topical antivirals provide only modest clinical benefit and are substantially less effective than oral therapy 1, 2, 3. Topical options include:

• Acyclovir 5% cream may reduce lesion duration if applied early 4, 6
• Topical ganciclovir 0.15% gel applied 3-5 times daily (less effective than oral therapy) 2
• Topical trifluridine 1% solution applied 5-8 times daily (not recommended for >2 weeks due to epithelial toxicity) 2

Topical antivirals are not effective for suppressive therapy as they cannot reach the site of viral reactivation in the nerve ganglia 1, 3.

Special Populations

Immunocompromised Patients

Episodes are typically longer and more severe, potentially involving the oral cavity or extending across the face 1:

• Initial treatment with IV acyclovir 5-10 mg/kg every 8 hours is recommended until clinical resolution 2
• Higher doses or longer treatment duration may be necessary 1, 2
• Continue treatment until complete healing of lesions 2
• Short-course therapy should not be used in HIV-infected patients 2
• Resistance rates are higher (acyclovir 7% vs <0.5% in immunocompetent patients) 7

Severe Infections Requiring Hospitalization

For severe oral HSV infections:

• IV acyclovir 5-10 mg/kg every 8 hours until clinical resolution 2
• Transition to oral therapy once lesions begin to regress to complete treatment 2
• Monitor renal function at initiation and once or twice weekly during IV therapy 2

Renal Impairment

Dose adjustment is necessary for patients with significant renal impairment 2, 3.

Management of Treatment Failure

If lesions do not begin to resolve within 7-10 days of therapy, suspect drug resistance 2:

• Obtain viral culture and perform susceptibility testing 2
• For confirmed acyclovir-resistant HSV, IV foscarnet (40mg/kg IV three times daily) is the treatment of choice 1, 2
• Resistance remains low (<0.5%) in immunocompetent hosts but may be higher in immunocompromised patients 1, 3

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, 8
• Serious neurologic adverse events (aggressive behavior, agitation, confusion, hallucinations, seizures) may occur, particularly in older adults or patients with renal impairment 8
• Monitor for renal toxicity, especially with IV acyclovir 2, 8

Common Pitfalls to Avoid

• Do not rely solely on topical treatments when oral therapy is significantly more effective 1, 3
• Do not use inadequate dosing—short-course, high-dose therapy is more effective than traditional longer courses 1, 3
• Do not start treatment too late—efficacy decreases significantly after lesions fully develop 1, 3
• Do not fail to consider suppressive therapy in patients with ≥6 recurrences per year who could significantly benefit 1
• Do not use topical corticosteroids, as they potentiate HSV epithelial infections 2

Preventive Counseling

Patients should identify and avoid personal triggers 1:

• Ultraviolet light exposure (use sunscreen SPF ≥15) 1, 4
• Fever 1
• Psychological stress 1
• Menstruation 1