What is the first line medication for herpes simplex?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: July 24, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

First-Line Medication for Herpes Simplex

Acyclovir is the first-line medication for herpes simplex virus infections, with specific dosing regimens depending on whether it is a first clinical episode or recurrent infection. 1

Treatment Regimens

First Clinical Episode

  • Recommended regimens 2, 1:
    • Acyclovir 400 mg orally three times a day for 7-10 days, OR
    • Acyclovir 200 mg orally five times a day for 7-10 days, OR
    • Famciclovir 250 mg orally three times a day for 7-10 days, OR
    • Valacyclovir 1 g orally twice a day for 7-10 days

Recurrent Episodes

  • Recommended regimens 2, 1:
    • Acyclovir 200 mg orally 5 times a day for 5 days, OR
    • Acyclovir 400 mg orally 3 times a day for 5 days, OR
    • Acyclovir 800 mg orally 2 times a day for 5 days

Treatment Approach Based on Frequency of Recurrence

Episodic Therapy

  • For patients with fewer than 6 outbreaks per year 1
  • Start treatment at first sign of prodrome or within 1 day of lesion onset
  • Use standard dosing regimens for recurrent episodes

Suppressive Therapy

  • For patients with 6 or more recurrences per year 2, 1
  • Reduces recurrence frequency by ≥75%
  • After 1 year of continuous suppressive therapy, consider discontinuing to reassess recurrence frequency

Special Considerations

Immunocompromised Patients

  • May require more aggressive therapy and longer treatment courses 1
  • Higher risk of treatment failure and development of acyclovir-resistant strains 3
  • For acyclovir-resistant HSV, foscarnet 40 mg/kg IV three times daily or 60 mg/kg IV twice daily is recommended 3

Renal Impairment

Dosage adjustment is necessary based on creatinine clearance 1, 4:

  • Creatinine clearance >10 mL/min/1.73m²:
    • 200 mg regimen: 200 mg every 4 hours
    • 400 mg regimen: 400 mg every 12 hours
    • 800 mg regimen: 800 mg every 4 hours
  • Creatinine clearance 0-10 mL/min/1.73m²:
    • 200 mg regimen: 200 mg every 12 hours
    • 400 mg regimen: 200 mg every 12 hours
    • 800 mg regimen: 800 mg every 12 hours

Severe Cases

  • Hospitalization and IV acyclovir (5-10 mg/kg every 8 hours) may be necessary for severe cases 1
  • Treatment may be extended if healing is incomplete after 10 days of therapy 2

Important Clinical Pearls

  1. Early treatment initiation: Maximum therapeutic benefit is achieved when treatment is started within the first 3 days of symptom onset 5, 6

  2. Topical therapy limitations: Topical acyclovir is substantially less effective than oral therapy and is not recommended 2, 1

  3. Persistence of latent virus: Acyclovir neither eradicates latent virus nor affects subsequent risk, frequency, or severity of recurrences after the drug is discontinued 2

  4. Patient counseling: Advise patients to abstain from sexual activity while lesions are present to prevent transmission 1

  5. Monitoring: For patients on high doses or with renal impairment, monitor for neurological symptoms (confusion, agitation, hallucinations) which may indicate acyclovir neurotoxicity 1

  6. Hydration: Adequate fluid intake during treatment is essential to minimize the risk of nephrotoxicity 1

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.