What are the recommended dosing regimens of Valtrex (valacyclovir) for primary genital herpes, recurrent genital outbreaks, suppressive therapy, oral herpes (cold sores), and herpes zoster in adults and children, and how should the doses be adjusted for impaired renal function?

Valtrex Dosing for Herpes

Genital Herpes (HSV-2)

First Episode

For primary genital herpes, prescribe valacyclovir 1 gram orally twice daily for 7–10 days, extending treatment if healing is incomplete after 10 days. 1

• Acyclovir 400 mg orally three times daily for 7–10 days is an effective alternative if valacyclovir is unavailable 1
• Treatment is most effective when initiated during the prodromal period or within 24 hours of lesion onset 1

Recurrent Episodes

For recurrent genital herpes outbreaks, use valacyclovir 500 mg orally twice daily for 5 days, initiated at the first sign of prodrome or within 24 hours of lesion appearance. 2, 1

• Alternative regimens include acyclovir 400 mg three times daily for 5 days or famciclovir 125 mg twice daily for 5 days 1
• Valacyclovir 1 gram once daily for 5 days is equally effective as 500 mg twice daily 3
• Provide patients with a prescription to self-initiate at the first sign of recurrence, as early treatment during prodrome significantly increases the chance of preventing vesicular or ulcerative lesions 1, 4

Suppressive Therapy

For immunocompetent patients with infrequent recurrences (<10 episodes/year), prescribe valacyclovir 500 mg once daily; for those with frequent recurrences (≥10 episodes/year), prescribe valacyclovir 1000 mg once daily. 2

• The 500 mg once-daily regimen is less effective in patients with ≥10 recurrences per year, who require the higher 1000 mg once-daily dose 2, 5
• Suppressive therapy reduces recurrence frequency by ≥75% in patients with frequent episodes 2
• Acyclovir 400 mg twice daily is an alternative with documented safety for up to 6 years of continuous use 2
• After 1 year of continuous suppressive therapy, discuss discontinuation to reassess recurrence frequency, as outbreak rates often decline over time 2

For HIV-infected patients with CD4+ count ≥100 cells/mm³, prescribe valacyclovir 500 mg twice daily—once-daily dosing is inadequate in this population. 2

• Twice-daily dosing is mandatory for HIV-infected patients; once-daily regimens do not provide sufficient viral suppression 2
• No laboratory monitoring is needed unless substantial renal impairment exists 2

Oral Herpes (HSV-1 Cold Sores)

Recurrent Episodes

For recurrent oral herpes, prescribe valacyclovir 500 mg orally twice daily for 5 days, initiated during prodrome or within 24 hours of lesion onset. 1

• Alternative regimens include acyclovir 400 mg three times daily for 5 days or famciclovir 125 mg twice daily for 5 days 1
• Peak viral replication occurs in the first 24 hours, making early initiation critical for efficacy 1

Suppressive Therapy for Frequent Recurrences

For patients with ≥6 oral herpes recurrences per year, prescribe valacyclovir 500 mg once daily for suppression, achieving at least a 75% reduction in recurrence frequency. 1

• Acyclovir 400 mg twice daily is an alternative with documented safety for up to 6 years 1
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 1

Herpes Zoster (Shingles)

Immunocompetent Adults

For uncomplicated herpes zoster in immunocompetent adults, prescribe valacyclovir 1000 mg orally three times daily for 7 days, continuing until all lesions have completely scabbed. 6, 7

• Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia 6
• Acyclovir 800 mg five times daily for 7–10 days is an alternative but requires more frequent dosing 6
• Do not discontinue at exactly 7 days if lesions are still forming or have not completely scabbed—continue treatment until all lesions have crusted 6
• Valacyclovir is superior to acyclovir in speeding the resolution of zoster-associated pain and postherpetic neuralgia 7, 4

Immunocompromised Patients

For immunocompromised patients with herpes zoster (including those on chemotherapy, HIV-infected, organ transplant recipients, or receiving chronic immunosuppression), initiate intravenous acyclovir 10 mg/kg every 8 hours, continuing for at least 7–10 days until all lesions have completely scabbed. 6

• Oral valacyclovir is inadequate for severely immunocompromised hosts; IV acyclovir is mandatory 6
• Consider temporary reduction or discontinuation of immunosuppressive medications in cases of disseminated or invasive herpes zoster if clinically feasible 6
• Monitor renal function at initiation and at least once or twice weekly during IV acyclovir therapy, adjusting doses for renal impairment 6

Disseminated or Complicated Herpes Zoster

For disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions), CNS complications, or complicated ocular/facial disease, switch to intravenous acyclovir 10 mg/kg every 8 hours regardless of immune status. 6

• Disseminated disease is defined by skin lesions in more than three dermatomes, visceral organ involvement (hepatitis, pneumonia, encephalitis), or hemorrhagic lesions 6
• If lesions fail to begin resolving within 7–10 days on appropriate therapy, suspect acyclovir resistance and obtain viral culture with susceptibility testing 6

Renal Dose Adjustments

For patients with creatinine clearance 30–49 mL/min receiving suppressive therapy, no dose reduction is needed; however, for treatment regimens and lower creatinine clearance, dose adjustments are mandatory to prevent acute renal failure. 2, 6

• Specific dose adjustments vary by indication and creatinine clearance; consult renal dosing guidelines for precise adjustments 6
• Advise adequate hydration to minimize nephrotoxicity risk in all patients taking valacyclovir 2

Acyclovir-Resistant HSV or VZV

If lesions persist despite appropriate valacyclovir treatment for 7–10 days, suspect antiviral resistance and switch to intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution. 2, 6

• All acyclovir-resistant strains are also resistant to valacyclovir 2, 6
• Resistance is rare (<0.5%) in immunocompetent patients but occurs in approximately 5–7% of immunocompromised patients 2, 6

Critical Pitfalls to Avoid

• Never use topical acyclovir alone—it is substantially less effective than systemic therapy and should not be used as sole treatment 2, 1
• Do not use once-daily valacyclovir dosing in HIV-infected patients—they require twice-daily dosing (500 mg BID) for adequate viral suppression 2
• Avoid high-dose valacyclovir (8 g/day) in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 2
• Do not delay treatment beyond 72 hours for herpes zoster—efficacy in preventing postherpetic neuralgia diminishes significantly after this window 6