Valacyclovir (Valtrex) Dosing for Herpes Simplex Virus Infections

Cold Sores (Herpes Labialis)

For cold sores, take valacyclovir 2 grams twice daily for 1 day (12 hours apart), initiated at the very first prodromal symptom. 1

This single-day, high-dose regimen reduces median episode duration to approximately 5.0 days versus 6.2 days with placebo, and shortens time to return to normal skin to 2.9 days versus 4.5 days 2
Critical timing requirement: Treatment must begin within the first 24 hours of symptoms (tingling, itching, burning)—any delay substantially reduces efficacy 2, 1
Patients should keep medication readily accessible for immediate self-initiation at first symptom 2
For pediatric patients ≥12 years, use the same adult dosing: 2 grams twice daily for 1 day 1

When to Consider Suppressive Therapy for Cold Sores

If ≥6 recurrences per year occur, discuss daily suppressive therapy with valacyclovir 500 mg once daily 2
Suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent outbreaks 2

Genital Herpes

First Clinical Episode

For initial genital herpes, prescribe valacyclovir 1 gram twice daily for 10 days, ideally started within 48 hours of symptom onset. 1, 3

Treatment may be extended beyond 10 days if healing is incomplete 3
This regimen is equivalent to acyclovir 200 mg five times daily for 7-10 days 4, 5
Note that 5-30% of first-episode genital herpes is caused by HSV-1, which has important prognostic implications (much less frequent recurrences than HSV-2) 3

Recurrent Episodes

For recurrent genital herpes, use valacyclovir 500 mg twice daily for 3 days, initiated at the first sign or symptom of an episode. 1

Alternative regimens with equivalent efficacy include:
- 1 gram once daily for 5 days 6
- 500 mg twice daily for 5 days 7, 8
The 3-day course is as effective as the 5-day course for all key efficacy markers (median time to healing: 4.4 vs 4.7 days) 8
Treatment is most beneficial when started during prodrome or within 2 days of lesion onset 4

Suppressive Therapy (Chronic Daily Prevention)

For patients with infrequent recurrences (≤9 episodes/year), prescribe valacyclovir 500 mg once daily; for frequent recurrences (≥10 episodes/year), use 1 gram once daily. 7, 1

The 500 mg once daily dose is significantly less effective in patients with ≥10 recurrences per year, who require the higher 1 gram daily dose 7
Suppressive therapy reduces recurrence frequency by ≥75% among patients with frequent episodes 7
Safety and efficacy documented for up to 1 year with valacyclovir and up to 6 years with acyclovir 7
After 1 year of continuous suppressive therapy, consider discontinuing to reassess recurrence frequency, as recurrences may decrease over time 7
No laboratory monitoring needed unless substantial renal impairment exists 7

Transmission Reduction

For immunocompetent source partners seeking to reduce transmission risk to uninfected partners, use valacyclovir 500 mg once daily. 1

This indication applies specifically to patients with ≤9 recurrences per year 1
Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 7, 3

Special Populations

HIV-Infected Patients

For HIV-infected patients with CD4+ count ≥100 cells/mm³, use valacyclovir 500 mg twice daily for suppressive therapy. 7, 3

Higher dosing is recommended for immunocompromised patients due to potentially more severe and frequent recurrences 7, 3
Critical safety warning: Avoid valacyclovir doses of 8 grams per day in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) 7, 3, 9
The TTP/HUS risk appears highest in patients with advanced HIV disease receiving prolonged high-dose therapy 9

Renal Impairment

No dose reduction needed for creatinine clearance ≥30 mL/min 7, 2
For significant renal impairment (CrCl <30 mL/min), dose adjustment is necessary 7
Advise adequate hydration to minimize nephrotoxicity risk 7

Pediatric Patients

For cold sores in children ≥12 years: 2 grams twice daily for 1 day 1
For chickenpox in children 2 to <18 years: 20 mg/kg three times daily for 5 days (maximum 1 gram three times daily) 1

Severe Disease Requiring Hospitalization

For severe HSV disease with complications (disseminated infection, encephalitis, pneumonitis, hepatitis), use IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days instead of oral valacyclovir. 4, 3

Oral valacyclovir is not appropriate for severe mucosal HSV infections requiring hospitalization 3

Treatment Failure and Resistance

If lesions persist after 7-10 days of appropriate valacyclovir therapy, suspect HSV resistance. 7, 3

All acyclovir-resistant HSV strains are also resistant to valacyclovir 7, 3
For acyclovir-resistant HSV, switch to IV foscarnet 40 mg/kg every 8 hours until clinical resolution 7, 3
Acyclovir-resistant strains have been isolated from patients on suppressive therapy but have not been associated with treatment failure in immunocompetent patients 4

Administration Considerations

Valacyclovir may be given without regard to meals 1
For pediatric patients unable to swallow tablets, an oral suspension (25 mg/mL or 50 mg/mL) can be prepared extemporaneously from 500-mg tablets 1
The prepared suspension must be stored refrigerated at 2-8°C and discarded after 28 days 1

Key Clinical Counseling Points

Patients should abstain from sexual activity while lesions are present 4
Sexual transmission can occur during asymptomatic periods without visible lesions 4
Condom use should be encouraged during all sexual exposures 4
Women of childbearing age with genital herpes should inform prenatal care providers about their HSV infection due to neonatal infection risk 4
The safety of valacyclovir in pregnancy has not been fully established, though current registry findings do not indicate increased risk for major birth defects compared to the general population 7

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