Acyclovir

Acyclovir 

  • Pregnancy Category B

Formulations

  • Topical, oral, intravenous (IV)

Dosing 

  • Immunocompetent
    • Herpes simplex virus infections (HSV)
      – 1st episode genital HSV: 200 mg 5x/day or 400 mg 3x/day for 10 days
      Recurrent
      • Orolabial HSV: 400 mg 3x/day for 7-10 days 
      • Genital HSV: 400 mg 3x/day or 800 mg 2x/day for 5 days 
      • Both 5% cream or ointment 5x/day for 5 day
    • Suppression: 400 mg twice daily
  • Varicella Zoster virus (VZV) infections:
    • Primary varicella: 20 mg/kg 4x/day (pediatrics) for 5-7 days [max = 800 mg 4x/day]
    • Herpes Zoster “shingles”: 800 mg 5x/day for 10 days to start within first 72 hours of symptom onset

Immunocompromised

  • Herpes simplex virus infections (HSV)
    – 400 mg 5x/day until lesions healed (or intravenous, see below
    • Recurrent genital in context of HIV: 400 mg 3x/day until lesions healed
      – Suppression in context of HIV: 400–800 mg 2-3x/day
  • Varicella Zoster virus (VZV) infections:
    • Primary varicella: 10 mg/kg q8h IV × 7–10 days 
    • Herpes Zoster: 10 mg/kg q8h IV × 7–10 days or until crusted and no new lesions

Indications for intravenous (IV) Acyclovir

  1. Failed oral treatment, cannot tolerate or non-compliant to oral therapy
  2. Complicated primary infection
  3. Disseminated herpes simplex or herpes zoster
  4. Neonatal HSV
  5. Extensive eczema herpeticum
  6. Acute severe herpes zoster affecting ophthalmic branch of trigeminal nerve “V1”
  7. Varicella zoster in adults with internal organ involvement
  8. Encephalitis or impaired mental capacity
  9. Immunocompromised host (HSV or VZV infections)

IV dosages

  • HSV
    • Neonatal HSV (14-21 days): 20 mg/kg q8h
    • Eczema herpeticum, especially if severe or in immunocompromised host (10-14 days or until all lesions healed): 5-10 mg/kg q8h
    • HSV in immunocompromised (until lesions healed): 5-10 mg/kg q8h
  • VZV
    • Primary varicella (in immunocompromised patients, including on chronic systemic corticosteroids): 10 mg/kg q8h for 7–10 days
    • Herpes Zoster in immunocompromised patient or disseminated VZV: 10 mg/kg q8h for 7–10 days or until crusted and no new lesions

  • Guanosine analogue, viral thymidine kinase dependent must be tri- phosphorylated to be pharmacologically active. Phosphorylated by herpes thymidine kinase (very portent in herpes simplex virus) then bi- and tri- phosphorylated by host enzymes leading to viral DNA polymerase inhibition. Incorporates tri-phosphorylated acyclovir instead of guanosine, terminating viral sequence
  • Bioavailability: 15-30%

FDA

  • Herpes simplex virus (HSV) infections: primary, recurrent, suppressive therapy
  • Varicella and herpes zoster
  • Includes immunocompromised patients

Off-label

  • Recurrent erythema multiforme and other HSV infections (e.g., neonatal HSV, eczema herpeticum)

  • Nausea, vomiting, and diarrhea
  • Headache
  • Skin hypersensitivity (with topical)
  • Intravenous: phlebitis, infusion site inflammation, reversible renal crystalline nephropathy

  • If combined with Foscarnet: risk of increased renal toxicity
  • Interferon and intrathecal methotrexate may increase acyclovir neurotoxicity
  • Interacts with mycophenolate: increases levels producing toxicity

  • Studies show suppressive treatment of herpes simplex virus in patients with HIV reduced risk of HIV progression and slows the drop of CD4+ level to below 350
  • Considerations for suppressive therapy with antivirals 
    1. 6 or more episodes per year
    2. Lack of prodromal symptoms 
    3. Severe outbreaks
    4. Seronegative partner
    5. Recurrent erythema multiforme
    6. Pregnant women before 36 weeks of gestation to reduce risk of perinatal transmission (who have genital HSV lesion anytime during pregnancy – whether with a primary, non-primary first-episode, or recurrent infection)