Acyclovir Dosing for Cold Sores (Herpes Labialis)
For cold sores, use acyclovir 800 mg orally twice daily for 5 days, initiated at the first sign of symptoms or within 2 days of lesion onset. 1, 2
Standard Treatment Regimens
The CDC provides three equally effective oral acyclovir regimens for episodic treatment of cold sores, all for 5 days duration: 1, 2
- Acyclovir 800 mg orally twice daily for 5 days (preferred for convenience and adherence) 1, 2
- Acyclovir 400 mg orally three times daily for 5 days 1, 2
- Acyclovir 200 mg orally five times daily for 5 days 1, 2
The 800 mg twice-daily regimen offers the best balance of efficacy and convenience, demonstrating shorter symptom duration (8.1 days vs 12.5 days with placebo, p=0.02) and reduced mean pain duration (2.5 days vs 3.9 days with placebo, p=0.02). 1
Critical Timing Considerations
Treatment must be initiated during the prodrome or within 2 days of lesion onset for maximum 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
Important Clinical Caveats
Effectiveness Limitations
- Most immunocompetent patients with recurrent cold sores experience only limited benefit from acyclovir therapy. 1, 2
- Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation. 1, 2
Route of Administration
- Oral acyclovir is significantly more effective than topical formulations and should always be preferred. 1, 2
- Topical acyclovir use is discouraged due to substantially inferior efficacy. 3
Special Populations
Immunocompromised Patients
For HIV-infected or otherwise immunocompromised patients who may have prolonged episodes with extensive disease: 2
- Acyclovir 400 mg orally three to five times daily until clinical resolution 2
- For severe cases: acyclovir 5-10 mg/kg IV every 8 hours 2
Frequent Recurrences (≥6 episodes per year)
For suppressive therapy that reduces recurrence frequency by at least 75%: 2
- Acyclovir 400 mg orally twice daily 2
- Alternative: 200 mg orally 3-5 times daily (to identify lowest effective dose) 2
Alternative Medications
If considering alternatives to acyclovir for improved convenience: 1
- Valacyclovir 2 g twice daily for 1 day provides comparable efficacy with superior convenience 1, 4
- Famciclovir 1500 mg single dose significantly reduces healing time (4.4 days vs 6.2 days with placebo, p<0.001) 1
Patient Counseling Points
- Patients should avoid close contact while active lesions are present to prevent transmission, though transmission can occur during asymptomatic periods. 1, 2
- Emphasize that acyclovir treats symptoms but does not cure the infection or prevent future recurrences. 1, 2
- Allergic reactions to acyclovir are infrequent. 2