What is the oral high dose treatment of valacyclovir (Valtrex) for a patient with shingles and no comorbidities, and what are the dose adjustments for impaired renal function at various estimated Glomerular Filtration Rate (eGFR) levels?

Valacyclovir Dosing for Shingles (Herpes Zoster)

Standard High-Dose Treatment

For an immunocompetent man with shingles and no comorbidities, the standard oral high-dose treatment is valacyclovir 1000 mg (1 gram) three times daily for 7 days. 1

• This regimen has been extensively validated and is the FDA-approved dosing for herpes zoster in immunocompetent adults 1
• Treatment should ideally be initiated within 72 hours of rash onset, though later initiation may still provide benefit 2
• A 14-day regimen showed no significant advantage over the 7-day regimen 2
• This dosing is superior to acyclovir in reducing the duration of zoster-associated pain and postherpetic neuralgia 2, 3

Renal Dose Adjustments by eGFR

The following dose adjustments are required based on creatinine clearance (which approximates eGFR): 1

eGFR ≥50 mL/min (Normal Renal Function)

• Dose: 1 gram every 8 hours (three times daily)
• No dose adjustment needed 1

eGFR 30-49 mL/min (Mild-Moderate Renal Impairment)

• Dose: 1 gram every 12 hours (twice daily)
• This represents a 33% reduction in daily dose 4, 1

eGFR 10-29 mL/min (Severe Renal Impairment)

• Dose: 1 gram every 24 hours (once daily)
• This represents a 67% reduction in daily dose 4, 1

eGFR <10 mL/min (End-Stage Renal Disease)

• Dose: 500 mg every 24 hours (once daily)
• This represents an 83% reduction from the standard dose 4, 1

Hemodialysis Patients

• Dose: 500 mg every 24 hours, administered after hemodialysis sessions 1
• During hemodialysis, approximately one-third of acyclovir is removed during a 4-hour session 1
• The half-life of acyclovir is approximately 14 hours in ESRD patients not on dialysis, but shortens to 4 hours during hemodialysis 1

Peritoneal Dialysis Patients

• Dose: 500 mg every 24 hours 1
• No supplemental doses are required after CAPD or CAVHD, as acyclovir removal is less pronounced than with hemodialysis 1

Important Clinical Considerations

Hydration is critical to minimize nephrotoxicity risk, particularly in patients with any degree of renal impairment. 5

• The acyclovir half-life increases from 2.5-3.3 hours in normal renal function to approximately 14 hours in ESRD 1
• Renal clearance of acyclovir represents 42% of total plasma clearance in patients with normal renal function 1
• No dosage modification is needed for patients with hepatic impairment (cirrhosis), as the rate but not extent of conversion to acyclovir is affected 1

Common Pitfalls to Avoid

• Do not use the lower doses recommended for genital herpes suppression (500 mg daily) to treat acute shingles - this is inadequate for herpes zoster 1
• Do not forget to adjust for renal function - failure to reduce the dose in renal impairment can lead to acyclovir accumulation and potential neurotoxicity 4, 1
• Do not use high-dose valacyclovir (8 grams/day) in any patient - this has been associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, particularly in immunocompromised patients 5, 6
• Ensure adequate hydration throughout the treatment course to protect renal function 5