Valacyclovir Renal Dosing
For patients with renal impairment, valacyclovir requires dose reduction based on creatinine clearance, with specific adjustments varying by indication: for CrCl 30-49 mL/min, most indications require no reduction except herpes zoster (1 gram every 12 hours); for CrCl 10-29 mL/min, reduce to 1 gram every 24 hours for herpes zoster and 500 mg every 24 hours for genital herpes; for CrCl <10 mL/min, reduce to 500 mg every 24 hours for herpes zoster and genital herpes. 1
Renal Dosing by Indication
Herpes Zoster
- CrCl ≥50 mL/min: 1 gram every 8 hours (standard dose) 1
- CrCl 30-49 mL/min: 1 gram every 12 hours 2, 1
- CrCl 10-29 mL/min: 1 gram every 24 hours 2, 1
- CrCl <10 mL/min: 500 mg every 24 hours 1
Genital Herpes (Recurrent Episodes)
- CrCl ≥50 mL/min: 500 mg every 12 hours for 5 days 1
- CrCl 30-49 mL/min: No dose reduction needed 1
- CrCl 10-29 mL/min: 500 mg every 24 hours 1
- CrCl <10 mL/min: 500 mg every 24 hours 1
Genital Herpes (Suppressive Therapy)
- CrCl ≥50 mL/min: 1 gram every 24 hours (or 500 mg every 24 hours for ≤9 recurrences/year) 1
- CrCl 30-49 mL/min: No dose reduction needed 3, 1
- CrCl 10-29 mL/min: 500 mg every 24 hours 1
- CrCl <10 mL/min: 500 mg every 24 hours (or 500 mg every 48 hours for patients with ≤9 recurrences/year) 1
Cold Sores (Herpes Labialis)
- CrCl ≥50 mL/min: 2 grams every 12 hours for 1 day (2 doses total) 1
- CrCl 30-49 mL/min: No dose reduction needed 1
- CrCl 10-29 mL/min: 1 gram every 24 hours 1
- CrCl <10 mL/min: 500 mg every 24 hours 1
Hemodialysis Patients
Administer the recommended dose after hemodialysis sessions. 1 During a 4-hour hemodialysis session, approximately one-third of acyclovir is removed, with a half-life of approximately 4 hours. 1
Peritoneal Dialysis Patients
Supplemental doses are not required following continuous ambulatory peritoneal dialysis (CAPD) or continuous arteriovenous hemofiltration/dialysis (CAVHD). 1 The removal of acyclovir is less pronounced than with hemodialysis, and pharmacokinetic parameters resemble those in end-stage renal disease patients not receiving hemodialysis. 1 However, case reports demonstrate that even adjusted doses can cause neurotoxicity in CAPD patients, with one case requiring 500 mg every 2 days for safe and effective treatment. 4
Critical Safety Considerations
Neurotoxicity Risk
- Avoid high-dose regimens (8 grams per day) in patients with renal impairment due to risk of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). 2, 3
- Renal impairment leads to proportionally higher concentrations of acyclovir and its metabolites (CMMG and 8-OH-ACV) in both systemic circulation and cerebrospinal fluid, increasing neurotoxicity risk. 5
- Neurotoxicity can occur even with preserved renal function in elderly patients, as demonstrated in an 88-year-old receiving 3,000 mg daily who developed impaired consciousness with acyclovir levels of 35.45 μg/mL in blood and 36.45 μg/mL in CSF. 6
Monitoring Requirements
- No routine laboratory monitoring is required for patients with normal renal function. 2
- Renal function monitoring is mandatory in patients with substantial renal impairment. 2
- Check BMP if clinical deterioration occurs or new symptoms suggest renal dysfunction. 2
- Patients with pre-existing renal impairment, hypertension, diabetes, concurrent nephrotoxic medications, or dehydration require baseline renal function documentation. 2
Practical Management Pearls
- Ensure adequate hydration to minimize nephrotoxicity risk, particularly in patients with pre-existing renal impairment. 3
- The bioavailability of acyclovir after valacyclovir administration is similar across diverse patient populations, including elderly patients, those with advanced HIV disease, and patients with impaired liver or renal function. 7
- Dosage reductions are only necessary when renal function is severely impaired. 7
- The elimination half-time in end-stage renal disease patients is approximately 15 hours compared to normal renal function. 4