What is the recommended dose of valacyclovir (Valtrex) for a patient with End-Stage Renal Disease (ESRD) and impaired renal function?

Valacyclovir Dosing in ESRD: Clarification

Yes, 500 mg once daily is the correct dose of valacyclovir for patients with ESRD (CrCl <10 mL/min), regardless of the indication. 1, 2

Definitive Dosing Recommendations

For ESRD Patients (CrCl <10 mL/min)

• The FDA-approved dosing for all indications in ESRD is 500 mg every 24 hours 2
• This applies uniformly whether treating:
  • Cold sores (herpes labialis) 2
  • Genital herpes (recurrent episodes) 2
  • Genital herpes (suppressive therapy in immunocompetent patients) 2
  • Genital herpes (suppressive therapy in HIV-infected patients) 2
  • Herpes zoster 2

Critical Dosing Details by Renal Function

The dose reduction follows a clear stepwise pattern based on creatinine clearance 1, 2:

• CrCl 30-49 mL/min: 500 mg to 1 g every 12 hours (depending on indication) 1
• CrCl 10-29 mL/min: 500 mg to 1 g every 24 hours 1
• CrCl <10 mL/min (ESRD): 500 mg every 24 hours for ALL indications 1, 2

Hemodialysis Considerations

• Patients on hemodialysis should receive 500 mg every 24 hours, administered AFTER dialysis sessions 2
• During a 4-hour hemodialysis session, approximately one-third of acyclovir is removed from the body 2
• The half-life of acyclovir during hemodialysis is approximately 4 hours, compared to 14 hours in ESRD patients not receiving dialysis 2

Peritoneal Dialysis Patients

• No supplemental dosing is required after CAPD or CAVHD 2
• The removal of acyclovir with peritoneal dialysis is less pronounced than hemodialysis, with dialysance of only 5.27 ml/min 3
• Less than 1% of an administered dose is recovered in 24-hour dialysate 3
• The pharmacokinetic parameters in peritoneal dialysis patients closely resemble ESRD patients not on dialysis 2

Critical Safety Warnings

Neurotoxicity Risk

• Valacyclovir neurotoxicity (VAN) is a common and preventable adverse effect when dosing is not adjusted for renal function 4
• In ESRD, the half-life extends to approximately 14 hours (compared to 2.5-3.3 hours in normal renal function), leading to drug accumulation 2, 5
• Failure to dose-adjust can result in severe neurological manifestations including confusion, hallucinations, and seizures requiring emergent hemodialysis 4

Pharmacokinetic Rationale

• Renal impairment increases systemic exposure to acyclovir and its metabolites (CMMG and 8-OH-ACV) proportionally in both plasma and CSF 5
• The apparent plasma clearance in dialysis patients is 86.3 ± 21.3 mL/min/1.73 m² compared to 679.16 ± 162.76 mL/min/1.73 m² in healthy subjects 2
• While CSF penetration ratios remain unchanged, the absolute concentrations in CSF are proportionally higher due to elevated plasma levels 5

Common Pitfall to Avoid

• Never use the standard dose of 1 gram three times daily (for herpes zoster) or 500 mg twice daily (for genital herpes) in ESRD patients 4
• Case reports document severe neurotoxicity when patients received six times the recommended dose due to failure to adjust for renal function 4
• Even with appropriate dosing at 500 mg every 2 days, treatment can be effective and well-tolerated in CAPD patients 3