What is the recommended dose of valacyclovir (Valtrex) for the treatment of Herpes Simplex Virus 1 (HSV-1)?

Valacyclovir Dosing for HSV-1

For HSV-1 infections, valacyclovir dosing depends on the clinical presentation: for orolabial herpes (cold sores), use 2 grams twice daily for 1 day taken 12 hours apart; for first-episode genital HSV-1, use 1 gram twice daily for 7-10 days; for recurrent genital HSV-1, use 500 mg twice daily for 3 days; and for suppressive therapy, use 500-1000 mg once daily depending on recurrence frequency. 1

Clinical Presentation-Specific Dosing

Orolabial Herpes (Cold Sores)

• Valacyclovir 2 grams twice daily for 1 day (12 hours apart) is the FDA-approved regimen for cold sores in patients ≥12 years of age 1
• Therapy should be initiated at the earliest symptom (tingling, itching, or burning) for maximum efficacy 1

First-Episode Genital HSV-1

• Valacyclovir 1 gram twice daily for 7-10 days is recommended for initial genital herpes episodes 2, 1
• Treatment is most effective when started within 48 hours of symptom onset 1
• Treatment may be extended if healing is incomplete after 10 days 2
• Note that 5-30% of first-episode genital herpes cases are caused by HSV-1, though clinical recurrences are much less frequent for HSV-1 than HSV-2 2

Recurrent Genital HSV-1

• Valacyclovir 500 mg twice daily for 3 days is the standard episodic treatment regimen 1
• Initiate treatment at the first sign or symptom of an episode 1
• This twice-daily regimen is equivalent in efficacy to acyclovir 200 mg five times daily but offers superior convenience 3

Suppressive Therapy for Recurrent Genital HSV-1

• For patients with ≤9 recurrences per year: valacyclovir 500 mg once daily 4, 1
• For patients with ≥10 recurrences per year: valacyclovir 1000 mg once daily 4, 1
• Daily suppressive therapy reduces recurrences by ≥75% among patients with frequent episodes 4
• Safety and efficacy have been documented for up to 1 year with valacyclovir 4
• After 1 year of continuous suppressive therapy, consider discussing discontinuation to reassess recurrence frequency 4

Severe HSV-1 Infections (Proctitis, Stomatitis, Pharyngitis)

• Higher dosages may be required for severe mucosal HSV-1 infections, though clinical experience with valacyclovir for these indications is limited 2
• For severe disease requiring hospitalization (disseminated infection, encephalitis, meningitis), IV acyclovir 5-10 mg/kg every 8 hours for 5-7 days should be used instead of oral valacyclovir 2

Special Populations

HIV-Infected Patients

• For suppressive therapy in HIV-infected patients with CD4+ count ≥100 cells/mm³: valacyclovir 500 mg twice daily 4, 1
• Higher dosing is recommended for immunocompromised patients due to potentially more severe and frequent recurrences 4
• Avoid valacyclovir doses of 8 grams per day in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 2, 4, 5

Renal Impairment

• For patients with creatinine clearance 30-49 mL/min, no dose reduction is needed 4
• For more severe renal impairment, dose adjustment is necessary 6
• No laboratory monitoring is needed for patients on suppressive therapy unless they have substantial renal impairment 4

Pregnancy

• The safety of valacyclovir in pregnant women has not been fully established 2, 4
• Current registry findings do not indicate an increased risk for major birth defects compared to the general population 4

Treatment Failure and Resistance

• If lesions persist despite appropriate valacyclovir treatment, consider HSV resistance 4
• All acyclovir-resistant HSV strains are also resistant to valacyclovir 2, 4
• For acyclovir-resistant HSV: IV foscarnet 40 mg/kg every 8 hours until clinical resolution is the treatment of choice 2, 4

Important Clinical Considerations

• Valacyclovir provides significantly better oral bioavailability than acyclovir, allowing for less frequent dosing 5, 7
• Valacyclovir may be given without regard to meals 1
• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 4
• HSV-1 genital infections have much less frequent clinical recurrences than HSV-2, which has important prognostic and counseling implications 2