Valacyclovir Dosing for Genital Herpes
For genital herpes in immunocompetent adults, use valacyclovir 1 gram twice daily for 10 days for initial episodes, 500 mg twice daily for 3 days for recurrent episodes, and 500 mg to 1 gram once daily for suppressive therapy depending on recurrence frequency. 1
Initial Episode Treatment
For the first episode of genital herpes, the FDA-approved dosing is 1 gram twice daily for 10 days 1. Therapy is most effective when initiated within 48 hours of symptom onset 1. This regimen has been shown to be as effective as acyclovir 200 mg five times daily in comparative trials 2.
Recurrent Episode Treatment
For recurrent outbreaks, 500 mg twice daily for 3 days is the recommended regimen 1. Treatment should be initiated at the first sign or symptom of an episode 1. Alternative dosing of 1000 mg once daily for 5 days has been shown to be equally effective as 500 mg twice daily 3, though the FDA label prioritizes the 3-day regimen 1.
Suppressive Therapy
The dosing for chronic suppression depends on recurrence frequency:
- For patients with 9 or fewer recurrences per year: 500 mg once daily 1, 4
- For patients with 10 or more recurrences per year: 1 gram once daily 1, 4, 5
The 500 mg once daily dose is less effective in patients with frequent recurrences (≥10 episodes per year), making the higher dose necessary for adequate suppression 6, 4. Suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent episodes 4, 6.
Additional Suppressive Therapy Benefits
- Reduces HSV-2 transmission to susceptible heterosexual partners by 50% when using 500 mg once daily 6
- Decreases asymptomatic viral shedding, though does not eliminate it entirely 4
- Safety and efficacy documented for up to 1 year of continuous use 4
Special Populations
HIV-Infected Patients
For HIV-infected patients with CD4+ count ≥100 cells/mm³:
- Suppressive therapy: 500 mg twice daily 1, 6, 4
- Acute treatment: 5-14 days of therapy (not the 1-3 day short-course regimens) 6
Important caveat: HIV-infected patients should never use abbreviated 1-3 day treatment regimens, as they require longer treatment durations of 5-14 days 6.
Renal Impairment
For patients with creatinine clearance 30-49 mL/min, no dose reduction is needed 4. However, patients with substantial renal impairment require dose adjustments and monitoring 4.
Monitoring and Safety
- No laboratory monitoring is required for patients on episodic or suppressive therapy unless substantial renal impairment exists 6
- Common adverse effects include headache and nausea, which are generally mild 6
- Valacyclovir may be given without regard to meals 1
Critical Safety Warning
Avoid high-dose valacyclovir (8 g/day) in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) 4. However, this complication has not been reported at standard doses used for HSV suppression 6.
Treatment Failure and Resistance
If lesions do not begin to resolve within 7-10 days of initiating therapy, suspect acyclovir resistance 6. All acyclovir-resistant strains are also resistant to valacyclovir 6, 4. For confirmed acyclovir-resistant HSV, IV foscarnet is the treatment of choice 6, 4.
Reassessment of Suppressive Therapy
After 1 year of continuous suppressive therapy, consider discussing discontinuation to assess recurrence frequency, as recurrences may decrease over time 4. This allows for reassessment of whether ongoing suppression remains necessary.