Acyclovir Prescription for Cold Sores (Oral Herpes Labialis)
For an otherwise healthy adult with recurrent cold sores, prescribe acyclovir 400 mg orally three times daily for 5 days, initiated at the first sign of prodrome or within 2 days of lesion onset. 1
Treatment Regimens for Episodic Recurrences
The CDC provides three equally effective oral acyclovir regimens for recurrent oral herpes, all for 5-day duration 1, 2:
- Acyclovir 400 mg orally 3 times daily for 5 days (preferred for balance of efficacy and convenience) 1
- Acyclovir 800 mg orally 2 times daily for 5 days 3, 1
- Acyclovir 200 mg orally 5 times daily for 5 days 3, 1
Alternative agents with superior convenience include valacyclovir 500-1000 mg twice daily for 5 days or famciclovir 1500 mg as a single dose 1.
Critical Timing for Maximum Benefit
Treatment must be initiated during the prodrome or within 2 days of lesion onset to achieve meaningful clinical benefit. 1, 2 Starting therapy after this window significantly reduces effectiveness, and most immunocompetent patients with recurrent disease experience limited benefit from delayed therapy 1, 2. Provide the patient with a prescription they can fill in advance and keep on hand to start immediately when symptoms begin 3.
Suppressive Therapy for Frequent Recurrences
For patients experiencing ≥6 recurrences per year, daily suppressive therapy reduces recurrence frequency by ≥75% 3, 1:
- Acyclovir 400 mg orally twice daily (continuous suppressive therapy) 3, 1
- Alternative: Valacyclovir 500 mg once daily 1
Research demonstrates that suppressive acyclovir (400 mg twice daily) extends median time to first recurrence from 46 days (placebo) to 118 days, representing a 53% reduction in clinical recurrences 4. Safety and efficacy have been documented for patients receiving daily acyclovir for up to 6 years 3. After 1 year of continuous suppressive therapy, reassess the patient to determine if continuation is needed, as recurrence frequency decreases over time in many patients 3.
Severe or Complicated Disease
For moderate to severe symptomatic gingivostomatitis or extensive mucocutaneous involvement requiring hospitalization 1, 5:
- Acyclovir 5-10 mg/kg IV every 8 hours 3, 1, 5
- Continue for 5-7 days or until clinical resolution 3, 1
- Switch to oral therapy (acyclovir 400 mg three times daily) once lesions begin to regress 1, 5
- Continue oral treatment until lesions completely heal 1
Essential Patient Counseling
Patients must understand that acyclovir neither eradicates latent virus nor affects subsequent recurrence risk, frequency, or severity after discontinuation. 1, 2 The virus remains dormant in nerve ganglia and will continue to reactivate periodically regardless of treatment 1.
Patients should abstain from activities that spread virus (kissing, sharing utensils, oral-genital contact) while lesions are present, though transmission can occur during asymptomatic periods 1, 2.
Common Pitfalls and Caveats
Topical acyclovir is significantly less effective than oral formulations and should not be relied upon as primary therapy. 1, 2 Oral antiviral medications are substantially more effective than topical formulations 2.
Renal dosing adjustments are required for patients with creatinine clearance <40 mL/min to prevent acute renal failure. 1 Ensure adequate hydration, as acyclovir is primarily renally excreted 5.
For immunocompromised patients, use higher doses (acyclovir 400 mg orally 3-5 times daily) and extend treatment duration to 7-14 days or until complete resolution 1, 5. Suspect acyclovir resistance if lesions fail to improve within 7-10 days of therapy, particularly in immunocompromised patients 1. Foscarnet 40 mg/kg IV every 8 hours is first-line treatment for confirmed resistance 1, 5.