What is the recommended treatment for oral herpes simplex in adults?

Management of Oral Herpes Simplex

For oral herpes simplex (herpes labialis/cold sores) in adults, initiate oral acyclovir 400 mg three times daily for 5 days, starting at the first sign of prodrome or within 2 days of lesion onset for maximum benefit. 1

First-Line Treatment Options

The CDC recommends three equally effective oral acyclovir regimens for recurrent oral herpes, all for 5-day duration: 1, 2

• Acyclovir 400 mg orally 3 times daily (preferred for balance of efficacy and convenience) 3, 1
• Acyclovir 800 mg orally 2 times daily 3, 1, 2
• Acyclovir 200 mg orally 5 times daily 3, 1

Alternative agents with superior convenience:

• Valacyclovir 500-1000 mg twice daily for 5 days 3, 4
• Famciclovir 1500 mg as a single dose (most convenient option, reduces healing time by ~2 days) 1, 5
• Famciclovir 500 mg twice daily for 5-7 days 5, 4

Critical Timing Considerations

Treatment must be initiated during the prodrome (tingling, itching, burning) or within 2 days of lesion onset to achieve meaningful clinical benefit. 1 Starting therapy after this window significantly reduces effectiveness, and most immunocompetent patients with recurrent disease experience limited benefit from delayed therapy. 1

Severe or Complicated Disease

For moderate to severe symptomatic gingivostomatitis or extensive mucocutaneous involvement requiring hospitalization: 3

• Acyclovir 5-10 mg/kg IV every 8 hours 3, 2
• Switch to oral therapy once lesions begin to regress 3
• Continue treatment until lesions completely heal 3

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 recurrences per year or frequent sun/stress-triggered episodes: 4

• Acyclovir 400 mg orally twice daily (reduces recurrence frequency by ≥75%) 2
• Valacyclovir 500 mg once daily 3
• Consider sunscreen alone (SPF ≥15) as non-pharmacologic prevention 4

Acyclovir-Resistant Disease

Suspect resistance if lesions fail to improve within 7-10 days of therapy, particularly in immunocompromised patients: 3

• Foscarnet 40 mg/kg IV every 8 hours (first-line for confirmed resistance) 3, 2
• Topical trifluridine, cidofovir, or imiquimod for external lesions (requires 21-28 days application) 3, 6
• Obtain viral culture with susceptibility testing to confirm resistance 3, 6

Important Clinical Caveats

Patient counseling is essential: 1

• Acyclovir neither eradicates latent virus nor affects subsequent recurrence risk, frequency, or severity after discontinuation 1
• Patients should abstain from activities that spread virus while lesions are present, though transmission can occur during asymptomatic periods 1
• Most immunocompetent patients with recurrent disease experience limited benefit from episodic therapy 1, 7

Topical antivirals (acyclovir cream, penciclovir, docosanol) are significantly less effective than oral formulations and should not be relied upon as primary therapy. 1 Oral antivirals are the standard of care. 1

Renal dosing adjustments are required for patients with creatinine clearance <40 mL/min to prevent acute renal failure. 2, 5 Monitor renal function when using high-dose IV acyclovir. 3

For immunocompromised patients (HIV, transplant, chemotherapy): 3, 2

• Use higher doses: acyclovir 400 mg orally 3-5 times daily 2
• Extend treatment duration to 7-14 days or until complete resolution 3, 2
• Maintain high suspicion for acyclovir resistance if lesions persist despite therapy 3, 2