What is the recommended dose of valacyclovir (Valtrex) for treating Herpes Simplex Virus (HSV) or Varicella-Zoster Virus (VZV) infections in pediatric patients and cardiac patients with impaired renal function?

Valacyclovir Dosing in Pediatric and Cardiac Patients

Pediatric Dosing Recommendations

For pediatric patients, valacyclovir dosing is weight-based at 20 mg/kg three times daily (maximum 1 gram per dose) for chickenpox in children aged 2 to <18 years, while children ≥12 years can receive adult dosing of 2 grams twice daily for cold sores. 1

Chickenpox (Varicella-Zoster Virus)

• The FDA-approved dosing for immunocompetent children aged 2 to <18 years is 20 mg/kg administered three times daily for 5 days, with a maximum single dose not exceeding 1 gram 1
• Therapy should be initiated at the earliest sign or symptom of chickenpox 1
• This weight-based approach produces favorable acyclovir blood concentrations and is well tolerated in children 3 months through 11 years of age 2

Cold Sores (Herpes Labialis)

• For adolescents aged ≥12 years, the CDC recommends 2 grams twice daily for 1 day, taken 12 hours apart 1
• Treatment should begin at the earliest symptom (tingling, itching, or burning) 1

Herpes Zoster and Severe VZV Infections

• For acute retinal necrosis or severe VZV disease, the CDC recommends initial IV acyclovir 10 mg/kg three times daily for 10-14 days, followed by valacyclovir 1 gram three times daily for 4-6 weeks for children old enough to receive adult dosing 3, 4
• For adolescents with zoster who can tolerate adult dosing, 1 gram three times daily for 7 days is recommended 4

Critical Age-Related Considerations

• Valacyclovir is NOT recommended for infants <3 months of age due to decreased clearance and significantly higher drug exposure (approximately 60% higher AUC) in this age group 2
• For children <12 years who cannot receive valacyclovir, acyclovir remains the preferred alternative at 20 mg/kg orally four times daily (maximum 800 mg/dose) 3, 5
• An extemporaneous oral suspension (25 mg/mL or 50 mg/mL) can be compounded from 500-mg valacyclovir tablets for pediatric patients unable to swallow solid dosage forms 1

Cardiac Patients with Renal Impairment

Valacyclovir requires mandatory dose adjustment in cardiac patients with impaired renal function, as acyclovir is primarily renally cleared and accumulation can lead to serious adverse effects. 4, 1

Renal Clearance and Pharmacokinetics

• Approximately 42% of total acyclovir clearance occurs via renal mechanisms (mean renal clearance 255 ± 86 mL/min in healthy subjects) 1
• In patients with end-stage renal disease (ESRD), the acyclovir half-life extends from 2.5-3.3 hours to approximately 14 hours 1
• During hemodialysis, approximately one-third of acyclovir is removed in a 4-hour session, with the half-life reduced to approximately 4 hours 1

Dose Adjustment Requirements

• The National Kidney Foundation mandates dose adjustment based on creatinine clearance (CrCl) for all patients with impaired renal function 4
• Dose reduction is required in geriatric cardiac patients, as renal function typically declines with age 1
• For patients on hemodialysis, dosing should be administered after dialysis sessions to account for drug removal 1

Monitoring Considerations

• Cardiac patients often have concurrent renal dysfunction; calculate estimated glomerular filtration rate (eGFR) before initiating therapy 6
• Ensure adequate hydration throughout treatment to prevent acyclovir crystalluria, particularly important in patients with compromised cardiac output 5, 7
• Monitor for signs of thrombotic microangiopathy (TMA) in immunocompromised patients receiving high-dose valacyclovir (≥8 g/day), as this potentially fatal syndrome has been reported 8

Common Pitfalls to Avoid

• Never use standard adult dosing in patients with renal impairment without adjustment—this can lead to neurotoxicity and other serious adverse effects 4, 1
• Cardiac patients on diuretics may have fluctuating renal function; reassess CrCl if clinical status changes 1
• Coadministration with probenecid increases acyclovir exposure by 49%, requiring additional dose reduction 1
• Cimetidine plus probenecid increases acyclovir AUC by 78%, primarily through reduced renal clearance 1

Alternative Considerations

• For cardiac patients with severe renal impairment who cannot tolerate adjusted oral dosing, IV acyclovir with appropriate dose reduction may be necessary 3
• Patients with hepatic impairment (cirrhosis) do not require dose modification, as the rate but not extent of conversion to acyclovir is affected 1