What is the recommended topical treatment for herpes simplex virus (HSV) infections on the lips?

Topical Treatment for Herpes Simplex Labialis (Cold Sores)

For herpes simplex labialis (cold sores on the lips), topical penciclovir 1% cream applied every 2 hours while awake for 4 days is the most effective topical antiviral option, reducing healing time by approximately 0.7 days and pain duration by 0.6 days compared to placebo. 1, 2

First-Line Topical Options

Penciclovir 1% cream (Denavir) is the preferred topical agent based on the strongest clinical evidence:

• Apply every 2 hours during waking hours for 4 consecutive days 1, 2
• Reduces median healing time from 5.5 days to 4.8 days (hazard ratio 1.33, P<.001) 2
• Decreases pain duration from 4.1 days to 3.5 days (P<.001) 2
• Effective when initiated at any stage—prodrome, erythema, papule, or vesicle stage 2
• Should be applied to lips and face only; avoid mucous membranes and eyes 1
• Well-tolerated with minimal adverse effects comparable to placebo 2

Docosanol 10% cream (Abreva) is an over-the-counter alternative:

• Apply 5 times daily at first sign of cold sore until healed 3
• Less robust evidence than penciclovir but available without prescription 3

Critical Timing Considerations

Treatment must be initiated within 1 hour of first symptoms for optimal efficacy 2:

• Start at earliest sign: tingling, redness, itching, or bump 1
• Efficacy demonstrated even when started at papule or vesicle stage, though earlier is better 2
• Treatment initiated beyond 48 hours shows diminished benefit 4

Important Limitations of Topical Therapy

Topical antivirals have significant limitations compared to oral therapy:

• Provide only modest clinical benefit (approximately 1 day reduction in symptoms) 5
• Not effective for prophylaxis as they cannot reach the site of viral reactivation in neurons 5, 6
• Less effective than oral antiviral agents (acyclovir, valacyclovir, famciclovir) 5, 4
• Require frequent application (every 2 hours for penciclovir), which may reduce adherence 5

When to Consider Oral Therapy Instead

Oral antivirals are superior and should be considered for:

• Patients with severe or frequent recurrences (≥6 episodes per year requiring chronic suppression) 4
• Patients desiring more convenient dosing regimens 5
• Initial primary herpetic gingivostomatitis (oral acyclovir 20 mg/kg up to 400 mg three times daily for 5-10 days) 6
• Immunocompromised patients 1

Supportive Care Measures

Adjunctive treatments to manage symptoms:

• Apply white soft paraffin ointment to lips every 2 hours for moisture and protection 5
• Use topical anesthetics (viscous lidocaine 2%) for pain control if needed 5
• Consider topical antiseptics to reduce bacterial colonization 5
• Sunscreen or zinc oxide may help prevent recurrences triggered by sun exposure 5

Common Pitfalls to Avoid

Do not use topical corticosteroids alone for HSV labialis:

• Corticosteroids potentiate HSV epithelial infections and should be avoided unless combined with antiviral therapy 5
• The combination of acyclovir/hydrocortisone cream (Xerese) has shown benefit but requires 5-6 times daily application 5

Avoid prolonged use of trifluridine:

• Causes inevitable epithelial toxicity if used for more than 2 weeks 5
• Not recommended for labial herpes (primarily used for ocular HSV) 5

Monitor for treatment failure:

• Lesions not improving or worsening should be evaluated for secondary bacterial infection 1
• Consider acyclovir-resistant HSV in immunocompromised patients with poor response 6