Valacyclovir

Valacyclovir

  • Pregnancy Category B

Formulations

  • Oral

Dosing

  • Herpes simplex virus (HSV) infections:
    • 1st episode: 1 g twice daily for 10 days (genital)
    • Recurrent: 500 mg twice daily for 3 days or 1 g daily for 5 days (genital)/ 2 g twice a day for 1 day (orolabial)
    • Immunocompromised 1g twice daily until lesion resolution
    • Suppression in immunocompetent host: 500 mg – 1 g daily depending on number of HSV outbreaks (10 per year is an initial cut-off); however, can increased based on response
    • Suppression in immunocompromised host: 500 mg twice daily
  • Varicella Zoster infections:
    • Primary varicella: 20 mg/kg (1 g max) 3x/day for 5 days
    • Herpes zoster “shingles”: 1 g 3x/day for 7 days to start within 72 hours of symptom onset
    • Immunocompromised see IV dosing for acyclovir

  • Prodrug of acyclovir (same mechanism of action of acyclovir): – – 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: 55% (3-5x more available than acyclovir)

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)

  • Headaches
  • Skin hypersensitivity
  • Thrombotic thrombocytopenic purpura (in HIV)
  • Rare gastrointestinal

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

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

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)