What are the recommended valacyclovir (Valcyclovir) dosing regimens for adults and children with herpes infections (primary genital herpes, recurrent genital herpes, herpes labialis, herpes zoster, varicella, CMV prophylaxis) and how should the dose be adjusted in renal impairment?

Valacyclovir Dosing Recommendations

Primary Genital Herpes (First Episode)

For primary genital herpes, prescribe valacyclovir 1000 mg orally twice daily for 10 days, which is as effective as acyclovir 200 mg five times daily but requires less frequent dosing. 1

• Valacyclovir 500 mg twice daily for 10 days is an equally effective alternative regimen 2, 1
• Treatment reduces viral shedding duration, hastens lesion healing, and decreases lesion-associated pain 3

Recurrent Genital Herpes (Episodic Treatment)

For recurrent episodes, prescribe valacyclovir 500 mg twice daily for 5 days, initiated at the first sign of prodromal symptoms or lesions. 4, 1

• Valacyclovir 1000 mg twice daily for 5 days is equally effective but offers no additional benefit over the 500 mg dose 1
• Early patient-initiated therapy significantly increases the chance of preventing vesicular or ulcerative lesions 5

Suppressive Therapy for Recurrent Genital Herpes

Immunocompetent Adults

For immunocompetent patients with infrequent recurrences (<10 episodes/year), prescribe valacyclovir 500 mg once daily; for those with frequent recurrences (≥10 episodes/year), prescribe 1000 mg once daily. 4

• Valacyclovir 500 mg once daily is less effective in patients with ≥10 recurrences per year 4
• Acyclovir 400 mg twice daily is an alternative with documented safety for up to 6 years 4
• Suppressive therapy reduces recurrence frequency by ≥75% 4
• After 1 year of continuous therapy, discuss discontinuation to reassess recurrence frequency, as outbreak rates often decline over time 4

HIV-Infected Patients

For HIV-infected adults with CD4+ count ≥100 cells/mm³, prescribe valacyclovir 500 mg twice daily—once-daily dosing is inadequate in this population. 4

• Twice-daily dosing is mandatory; once-daily regimens do not provide sufficient viral suppression 4
• Daily suppressive therapy reduces HIV RNA concentrations in plasma and genital secretions 4

Herpes Labialis (Oral Herpes)

For recurrent herpes labialis, prescribe valacyclovir 2000 mg twice daily for 1 day (total 4 grams), initiated at the earliest sign of prodrome.

• Limited data exist for valacyclovir in oro-facial herpes; acyclovir 400 mg twice daily is an alternative for suppressive therapy 4

Herpes Zoster (Shingles)

Immunocompetent Adults

For herpes zoster in immunocompetent adults, prescribe valacyclovir 1000 mg orally three times daily for 7 days, initiating therapy within 72 hours of rash onset. 6

• Treatment is most effective when started within 48–72 hours but may still provide benefit if initiated later 6
• Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period 7
• Valacyclovir is superior to acyclovir in reducing the duration of zoster-associated pain and post-herpetic neuralgia 6, 3

Immunocompromised Adults

For immunocompromised patients with uncomplicated herpes zoster, use oral acyclovir 800 mg five times daily rather than valacyclovir, as high-dose valacyclovir (8 g/day) carries risk of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome. 6, 8

• For severe disease with complications (disseminated infection, pneumonitis, hepatitis, CNS involvement), use intravenous acyclovir 10 mg/kg every 8 hours for at least 7–10 days until all lesions have scabbed 6, 7
• Temporarily reduce or discontinue immunosuppressive medications when clinically feasible 7

Pediatric Patients

For adolescents ≥12 years able to tolerate adult dosing, prescribe valacyclovir 1000 mg three times daily for 7 days. 6

• For children <12 years, use acyclovir 20 mg/kg orally four times daily (maximum 800 mg per dose) 9, 6
• For severe VZV disease or acute retinal necrosis in children eligible for adult dosing, use intravenous acyclovir 10 mg/kg three times daily for 10–14 days, followed by oral valacyclovir 1000 mg three times daily for 4–6 weeks 9, 6

Varicella (Chickenpox)

Children with Mild to Moderate Immunosuppression

For children with chickenpox and mild to moderate immune suppression, prescribe acyclovir 20 mg/kg orally four times daily (maximum 800 mg/dose) for 7–10 days or until no new lesions appear for 48 hours. 9

Severe Immunosuppression

For children with severe immunosuppression, use intravenous acyclovir 10 mg/kg every 8 hours. 9

• Some experts base IV acyclovir dosing in children aged >1 year on body surface area (500 mg/m²/dose IV every 8 hours) instead of body weight 9

CMV Prophylaxis

For CMV prophylaxis in renal transplant recipients, valacyclovir 2000 mg four times daily for 90 days significantly reduces CMV disease incidence and delays onset. 8

• In CMV-seronegative recipients receiving kidneys from CMV-seropositive donors, valacyclovir reduced CMV disease incidence to 3% versus 45% with placebo 8
• Do not use valacyclovir 8 g/day in patients with advanced HIV disease due to increased mortality risk and thrombotic microangiopathy. 8

Renal Dose Adjustments

Valacyclovir dosing must be adjusted according to creatinine clearance in patients with reduced renal function. 6

Herpes Zoster Dosing Adjustments

• CrCl 30–49 mL/min: 1000 mg every 12 hours
• CrCl 10–29 mL/min: 1000 mg every 24 hours
• CrCl <10 mL/min: 500 mg every 24 hours

Genital Herpes Episodic Treatment Adjustments

• CrCl 10–29 mL/min: 500 mg every 24 hours
• CrCl <10 mL/min: 500 mg every 24 hours

Suppressive Therapy Adjustments

• CrCl <30 mL/min (immunocompetent): 500 mg every 24 hours (for patients requiring 1000 mg daily)
• CrCl <30 mL/min (HIV-infected): 500 mg every 24 hours

Critical Monitoring

Assess baseline renal function before initiating therapy and monitor at least once or twice weekly during intravenous acyclovir treatment. 7

• Maintain adequate hydration throughout therapy to minimize nephrotoxicity risk 4, 7
• Adjust dosing immediately if renal function deteriorates 7

Management of Treatment Failure and Resistance

If HSV or VZV lesions fail to begin resolving within 7–10 days of appropriate valacyclovir therapy, suspect antiviral resistance and obtain viral culture with susceptibility testing. 4, 7

• All acyclovir-resistant strains are also resistant to valacyclovir 4
• For confirmed acyclovir-resistant HSV or VZV, use intravenous foscarnet 40 mg/kg every 8 hours until clinical resolution 4, 7
• Resistance rates are <0.5% in immunocompetent patients but 5–7% in immunocompromised patients 4

Critical Pitfalls to Avoid

• Never use topical acyclovir as sole therapy—it is substantially less effective than systemic treatment 4, 7
• Do not use short-course regimens (1–3 days) designed for genital herpes to treat herpes zoster—they are inadequate for VZV infection 7
• Avoid valacyclovir doses of 8 g/day in immunocompromised patients due to risk of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome 6, 4
• Do not postpone antiviral therapy awaiting laboratory confirmation in herpes zoster—initiate treatment based on clinical presentation within 72 hours of rash onset 6