What are the dosing recommendations for Valtrex (valacyclovir) for genital herpes, recurrent genital herpes, cold sores, and shingles in healthy adults, and how should the dose be adjusted in renal impairment?

Valtrex (Valacyclovir) Dosing Guide

Cold Sores (Herpes Labialis)

For cold sores, give valacyclovir 2 grams twice daily for 1 day (12 hours apart), starting at the earliest symptom such as tingling, itching, or burning. 1

• This high-dose, single-day regimen reduces median episode duration by approximately 1 day compared to placebo and offers superior convenience over traditional multi-day courses 2
• Treatment must be initiated during the prodromal phase or within 24 hours of lesion onset to achieve optimal benefit, as peak viral titers occur in the first 24 hours 2
• Starting treatment after the first 24 hours markedly diminishes clinical efficacy 2
• Alternative regimens include famciclovir 1500 mg as a single dose or acyclovir 400 mg five times daily for 5 days, though these require more frequent dosing 2

Suppressive Therapy for Frequent Cold Sores

• For patients with ≥6 recurrences per year, use valacyclovir 500 mg once daily 2
• For very frequent recurrences (≥10 episodes/year), increase to valacyclovir 1000 mg once daily 2
• Daily suppressive therapy reduces recurrence frequency by ≥75% 2
• After 1 year of continuous suppressive therapy, consider discontinuation to reassess recurrence frequency 2

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Genital Herpes

Initial Episode

For first-episode genital herpes, give valacyclovir 1 gram twice daily for 10 days, ideally started within 48 hours of symptom onset. 1

Recurrent Episodes

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

• Alternative episodic regimens include acyclovir 400 mg three times daily for 5 days, acyclovir 800 mg twice daily for 5 days, or famciclovir 125 mg twice daily for 5 days 3
• Episodic therapy is most effective when started during prodrome or within 1 day of lesion onset 3

Suppressive Therapy for Recurrent Genital Herpes

For chronic suppression in immunocompetent patients, give valacyclovir 1 gram once daily. 1

• For patients with a history of ≤9 recurrences per year, an alternative dose is valacyclovir 500 mg once daily 1
• In HIV-infected patients with CD4+ count ≥100 cells/mm³, use valacyclovir 500 mg twice daily 1
• Suppressive therapy reduces recurrence frequency by ≥75% and decreases asymptomatic viral shedding 3
• Safety and efficacy documented for acyclovir up to 6 years and valacyclovir up to 1 year of continuous use 3
• After 1 year of suppressive therapy, consider discontinuation to reassess recurrence frequency 3

Transmission Reduction

• For reduction of transmission in source partners with ≤9 recurrences per year, use valacyclovir 500 mg once daily 1

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Herpes Zoster (Shingles)

For shingles, give valacyclovir 1 gram three times daily for 7 days, starting within 48 hours of rash onset. 1

• Therapy should be initiated at the earliest sign or symptom of herpes zoster 1
• Valacyclovir is significantly more effective than acyclovir in reducing the duration of zoster-associated pain 4

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Renal Dose Adjustments

Renal function must be assessed before initiating valacyclovir, especially in elderly patients (≥80 years), to allow appropriate dose adjustment and avoid neurotoxicity. 2

While the FDA label 1 provides detailed renal dosing tables, key principles include:

• Dose adjustments required based on creatinine clearance 2
• Reducing frequency (not individual dose) is the typical adjustment strategy 2
• Failure to adjust doses in renal impairment risks drug accumulation and neurotoxicity 2

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Critical Clinical Considerations

Timing Is Everything

• Early initiation during prodrome or within 24 hours of symptoms is essential for all HSV infections 5, 2
• Delayed treatment after 24 hours significantly reduces efficacy 2

Resistance Patterns

• Acyclovir resistance remains rare (<0.5%) in immunocompetent patients 2
• Immunocompromised patients have substantially higher resistance rates (approximately 7%) 2
• For confirmed acyclovir-resistant HSV, use foscarnet 40 mg/kg IV three times daily 2

Common Pitfalls to Avoid

• Never use topical acyclovir—it is substantially less effective than oral therapy 5, 3
• Do not use valacyclovir 8 grams per day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 3
• Valacyclovir 500 mg once daily is less effective in patients with ≥10 recurrences per year; use 1 gram once daily instead 5

Transmission Counseling

• Suppressive therapy reduces but does not eliminate asymptomatic viral shedding 5, 2
• Patients remain contagious until all lesions are fully crusted 2
• Abstain from sexual activity when lesions or prodromal symptoms are present 5, 3
• Asymptomatic shedding can occur even on suppressive therapy, so transmission risk persists 2
• Use condoms during all sexual exposures with new or uninfected partners 3

Safety Profile

• Valacyclovir is generally well tolerated with minimal adverse events 2
• Most common side effects: headache (<10%), nausea (<4%), and diarrhea, typically mild to moderate 2
• Comparable safety profile to acyclovir and placebo 5

Trigger Avoidance

• Counsel patients to identify and avoid personal triggers: UV light exposure, fever, psychological stress, menstruation 2
• Applying sunscreen (SPF ≥15) or zinc oxide before sun exposure can prevent UV-triggered recurrences 2