Acyclovir 5% Cream for Herpes Simplex Virus Infections
Acyclovir 5% cream should be applied 5 times daily for 5 days, but oral acyclovir is strongly preferred over topical formulations because topical therapy is substantially less effective and its use is discouraged for treating herpes simplex infections. 1
Why Topical Acyclovir 5% Cream is Not Recommended
- The CDC explicitly states that topical acyclovir therapy is substantially less effective than oral formulations and its use is discouraged for treating herpes simplex infections. 1
- The limited efficacy of topical acyclovir results from inadequate penetration of the drug into the basal epidermis, which is the target site of HSV infection 2
- While penciclovir 1% cream demonstrates better skin penetration than acyclovir 5% cream in reaching deeper epidermal layers, oral therapy remains superior for all HSV infections 3
Recommended Oral Alternatives (Preferred Over Topical)
For First Episode Genital Herpes:
- Acyclovir 400 mg orally 3 times daily for 7-10 days 4
- Alternative: Acyclovir 200 mg orally 5 times daily for 7-10 days 4, 1
- Treatment may be extended if healing is incomplete after 10 days 4
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 5, 1
- Alternative: Acyclovir 200 mg orally 5 times daily for 5 days 5, 1
For Oral Herpes (Cold Sores/Herpes Labialis):
- Acyclovir 800 mg orally twice daily for 5 days (most convenient regimen with equivalent efficacy) 5
- Alternative: Acyclovir 400 mg orally 3 times daily for 5 days 5
- Alternative: Acyclovir 200 mg orally 5 times daily for 5 days 5
Critical Timing for Treatment Initiation
- Treatment must be initiated during the prodrome or within 2 days of lesion onset for maximum benefit 5, 1
- Starting therapy after this window significantly reduces effectiveness 5, 1
- Mortality from HSV encephalitis decreased to 8% when acyclovir therapy was initiated within 4 days of symptom onset, compared to 28% overall mortality 4
Special Populations Requiring More Aggressive Therapy
Immunocompromised Patients:
- Require oral or intravenous therapy rather than topical treatment due to risk of severe and prolonged episodes 1
- Acyclovir 400 mg orally 3-5 times daily, or higher doses may be needed 1, 6
- May require IV acyclovir 5-10 mg/kg every 8 hours for extensive disease 1
Severe or Disseminated Disease:
- IV acyclovir 10 mg/kg every 8 hours for 14-21 days for HSV encephalitis 4
- For neonatal HSV encephalitis: 20 mg/kg IV every 8 hours for 21 days (reduces mortality to 5%) 4
- Hospitalized patients with disseminated infection, pneumonitis, hepatitis, or CNS complications require IV therapy 1
Moderate to Severe Gingivostomatitis in Children:
- Acyclovir 5-10 mg/kg IV 3 times daily initially, then switch to oral therapy once lesions begin to regress 4
- Continue until lesions completely heal 4
Important Clinical Caveats
- Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after discontinuation 5, 1, 7
- Most immunocompetent patients with recurrent disease experience limited benefit from therapy overall 5, 1
- Patients should abstain from activities that might spread the virus while lesions are present 5, 1
- Transmission can occur during asymptomatic periods, particularly in the first 12 months after infection 4
- Dosage adjustment is required in patients with renal failure due to renal excretion 7
Acyclovir-Resistant HSV
- For acyclovir-resistant HSV: Foscarnet 40 mg/kg IV 3 times daily or 60 mg/kg IV twice daily 4, 8
- Resistance typically develops in immunocompromised patients with frequent, severe reactivations 8
- If foscarnet fails, consider IV cidofovir or topical cidofovir 1-3% ointment 8
Enhanced Topical Formulation (If Topical Must Be Used)
- A combination cream containing acyclovir 5% plus hydrocortisone 1% has shown superior efficacy to acyclovir 5% cream alone by reducing the immune-mediated inflammatory response 9
- This combination significantly reduced ulcerative and nonulcerative HSL lesions and shortened healing time 9
- However, oral therapy remains the preferred approach per CDC guidelines 1