Acyclovir Ointment for Herpes Simplex Infections
Acyclovir ointment should NOT be used for treating herpes simplex virus infections—oral acyclovir is strongly preferred because topical therapy is substantially less effective and its use is explicitly discouraged by the CDC. 1
Why Topical Acyclovir Fails
The CDC has consistently stated across multiple guideline iterations that topical acyclovir therapy is substantially less effective than oral formulations. 2, 1 This is not a minor difference in efficacy—the clinical benefit is so limited that guidelines explicitly discourage its use. 1
While some research suggests that 5% acyclovir cream may reduce lesion duration if applied very early, 3 this modest benefit does not justify its use when superior oral alternatives are readily available. The cream formulation requires application 5 times daily for 5 days, 1 which is burdensome and still produces inferior outcomes compared to oral therapy.
Recommended Oral Alternatives Instead
For first episode genital herpes:
- Acyclovir 200 mg orally 5 times daily for 7-10 days until clinical resolution 2, 1
- Alternative: Acyclovir 400 mg orally 3 times daily for 7-10 days 2
For recurrent genital herpes:
- Acyclovir 800 mg orally twice daily for 5 days 1
- Alternative: Acyclovir 400 mg orally 3 times daily for 5 days 1
- Alternative: Acyclovir 200 mg orally 5 times daily for 5 days 1
For recurrent herpes labialis (cold sores):
- Acyclovir 400 mg orally 3 times daily for 3-5 days 3
- A 2-day regimen of 800 mg orally 3 times daily has also proven effective 4
Critical Timing Considerations
Treatment must be initiated during the prodrome or within 2 days of lesion onset for maximum benefit. 1 Starting therapy after this window significantly reduces effectiveness. 1 For oral herpes labialis, when treatment started within 1 hour of first symptoms in the prodrome or erythema stage, oral acyclovir reduced pain duration by 36% and healing time by 27%. 5
This timing requirement is one reason why topical therapy often fails in real-world practice—by the time patients apply cream, the critical window has often passed.
When IV Therapy Is Required
Immunocompromised patients require more aggressive therapy with acyclovir 400 mg orally 3-5 times daily or IV administration at 5-10 mg/kg every 8 hours. 1
Hospitalized patients with disseminated infection, pneumonitis, hepatitis, or CNS complications require IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days. 1
Severe mucocutaneous HSV lesions warrant immediate IV acyclovir 10 mg/kg every 8 hours, even if diagnostic confirmation is pending. 6
Important Limitations to Discuss with Patients
Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation. 2, 1 This applies to all formulations—oral, topical, and IV. 7
Most immunocompetent patients with recurrent disease experience limited benefit from therapy overall, 1 which is why suppressive therapy (acyclovir 400 mg orally 2-3 times daily) may be more appropriate for patients with frequent recurrences (≥6 per year). 2
Common Pitfalls to Avoid
- Never prescribe topical acyclovir as primary therapy when oral formulations are available and appropriate 1, 8
- Do not delay treatment waiting for viral culture confirmation—start oral therapy immediately when HSV is clinically suspected 1
- Do not underdose immunocompromised patients—they require higher doses or IV therapy, not topical formulations 1
- Do not use topical therapy for herpes zoster—it is completely ineffective for this indication 8