Topical Acyclovir Cream for Herpes Simplex Virus Infections
Topical acyclovir cream is substantially less effective than oral therapy and its use is discouraged for treating herpes simplex virus infections. 1
Why Topical Therapy Is Not Recommended
The CDC explicitly states that topical therapy with acyclovir is substantially less effective than oral formulations based on randomized controlled trials. 1 This recommendation applies to all forms of HSV infection, including:
Limited Role for Topical Agents
Topical formulations have only a narrow indication:
- Acyclovir-resistant HSV in immunocompromised patients: Topical trifluridine, cidofovir, or imiquimod may be used for lesions on external surfaces, but require prolonged application for 21-28 days or longer 1
- 5% acyclovir cream: May reduce lesion duration if applied very early in recurrent herpes labialis, though benefit is modest 3
What to Use Instead
For oral/labial herpes (cold sores), the recommended oral regimens are: 2
- Acyclovir 200 mg orally 5 times daily for 5 days, OR
- Acyclovir 400 mg orally 3 times daily for 5 days, OR
- Acyclovir 800 mg orally 2 times daily for 5 days
For first episode genital herpes: 1
- Acyclovir 200 mg orally 5 times daily for 7-10 days until clinical resolution
For severe disease or immunocompromised patients: 1
- IV acyclovir is preferred over any topical or oral therapy
Critical Timing Consideration
Treatment should be initiated during the prodrome or within 2 days of lesion onset for maximum benefit. 2 Most immunocompetent patients with recurrent disease experience limited benefit from therapy regardless of formulation. 1, 2
Common Pitfall
Do not prescribe topical acyclovir cream thinking it will avoid systemic side effects—the trade-off in efficacy is not worth it, and oral acyclovir has an excellent safety profile with only occasional nausea or headache. 1