What is more effective for treating cold sores in adults and adolescents with a normal immune system, antiviral cream or antiviral ointment?

Cold Sores: Oral Therapy Over Topical Formulations

For cold sores in adults and adolescents with normal immune function, oral antiviral therapy is definitively superior to topical formulations (whether cream or ointment), and the choice between topical cream versus ointment is clinically irrelevant since neither should be first-line treatment. 1, 2

Why Oral Therapy is Superior

The evidence strongly favors oral antivirals over any topical formulation:

• Oral antivirals reduce episode duration by approximately 1 day, while topical antivirals provide only "small clinical benefit" with modest reductions in symptom duration 1
• Topical formulations fail to adequately penetrate to the basal epidermis where HSV replicates, limiting their effectiveness 3
• Oral therapy is more convenient (1-2 day treatment course vs. applying topical agents 5-6 times daily for 4-5 days) and improves patient adherence 1

First-Line Oral Treatment Options

When treating cold sores, prioritize these oral regimens:

• Valacyclovir 2g twice daily for 1 day - this is the preferred first-line treatment, reducing median episode duration by 1.0 day compared to placebo 2, 4
• Famciclovir 1500mg as a single dose - equally effective alternative with convenient single-day dosing 2, 5
• Acyclovir 400mg five times daily for 5 days - effective but requires more frequent dosing 2, 5

Treatment must be initiated within 24 hours of symptom onset, ideally during the prodromal stage (itching, burning sensation before visible lesions) to achieve maximum benefit 2, 5

When Topical Agents Have Any Role

Topical products have extremely limited utility:

• White soft paraffin ointment (not antiviral) applied every 2 hours can provide symptomatic relief and prevent cracking 2
• Topical anesthetics like benzydamine hydrochloride can help manage pain 2
• Topical penciclovir 1% cream is FDA-approved for cold sores 6 and showed modest benefit (0.7 day faster healing) when applied every 2 hours while awake for 4 days 7, but this is still inferior to oral therapy
• The combination of acyclovir 5% with hydrocortisone 1% cream showed some benefit in preventing ulcerative lesions 1, 8, but requires 5-6 times daily application making it less practical than oral therapy 1

Critical Pitfalls to Avoid

• Do not rely solely on topical antivirals when oral therapy is indicated - this is the most common error in cold sore management 2, 5
• Do not use topical antivirals for suppressive therapy in patients with frequent recurrences (≥6 episodes/year) - they cannot reach the site of viral reactivation in sensory ganglia and are completely ineffective for prevention 1, 5
• Do not delay treatment - efficacy decreases dramatically when treatment starts after lesions fully develop, as peak viral titers occur in the first 24 hours 2, 5

Suppressive Therapy for Frequent Recurrences

For patients experiencing 6 or more cold sore episodes per year:

• Valacyclovir 500mg once daily (can increase to 1000mg daily for very frequent recurrences) is first-line suppressive therapy 2, 5
• Daily suppressive therapy reduces recurrence frequency by ≥75% 2, 5
• Famciclovir 250mg twice daily or acyclovir 400mg twice daily are alternatives 5
• Only oral antivirals work for suppression - topical formulations are ineffective 1, 5

Safety Considerations

• Oral antivirals are generally well-tolerated with minimal adverse events 2, 5
• Common side effects include headache (<10%), nausea (<4%), and mild gastrointestinal disturbances 5
• Resistance development with episodic use in immunocompetent patients is rare (<0.5%) 2, 5