Aciclovir Dosage Adjustment in Chronic Kidney Disease
Yes, CKD significantly affects aciclovir dosage and requires mandatory dose reduction based on creatinine clearance to prevent drug accumulation and nephrotoxicity. 1
Dosage Adjustment Algorithm
Aciclovir is almost entirely eliminated by the kidneys, with a terminal half-life of 2-3 hours in normal renal function that extends to approximately 19.5 hours in end-stage renal disease. 2 This dramatic prolongation necessitates careful dose modification. 3
Specific Dose Adjustments by Indication and Renal Function
For standard 200 mg every 4 hours (5 times daily) regimen: 1
- CrCl >10 mL/min: 200 mg every 4 hours, 5 times daily (no adjustment)
- CrCl 0-10 mL/min: 200 mg every 12 hours
For 400 mg every 12 hours regimen: 1
- CrCl >10 mL/min: 400 mg every 12 hours (no adjustment)
- CrCl 0-10 mL/min: 200 mg every 12 hours
For 800 mg every 4 hours (herpes zoster) regimen: 1
- CrCl >25 mL/min: 800 mg every 4 hours, 5 times daily (no adjustment)
- CrCl 10-25 mL/min: 800 mg every 8 hours
- CrCl 0-10 mL/min: 800 mg every 12 hours
Oral vs. Intravenous Considerations
The FDA-approved dosing adjustments apply to oral aciclovir, though the principles extend to IV formulations. 1 For IV aciclovir specifically, dose adjustments should be even more stringent given the higher risk of acute kidney injury, particularly in patients with pre-existing CKD. 4
Hemodialysis Patients
Aciclovir is readily dialyzable with a dialysis clearance of approximately 82 mL/min and an extraction coefficient of 0.45. 2 The terminal half-life during hemodialysis decreases to approximately 5.7 hours. 2
- Dosing schedule: Adjust to the lowest frequency based on CrCl 0-10 mL/min recommendations, then administer an additional dose after each dialysis session 1, 5
- Timing: The supplemental dose should be given post-dialysis on dialysis days 5
Peritoneal Dialysis
No supplemental dose appears necessary after adjusting the dosing interval according to the CrCl 0-10 mL/min recommendations. 1
Critical Safety Considerations
Risk factors for aciclovir-induced nephrotoxicity include: 4, 6
- Pre-existing chronic kidney disease (most significant independent risk factor)
- Higher total daily doses
- Rapid IV bolus administration (for parenteral formulations)
- Inadequate hydration or fluid restriction
- Advanced age
The incidence of acute kidney injury with parenteral aciclovir is approximately 13%, with half being KDIGO grade 2/3. 4 This risk is comparable to established nephrotoxic agents like aminoglycosides. 4
Monitoring Requirements
- Calculate creatinine clearance before initiating therapy using validated calculators 7
- Monitor serum creatinine during treatment, particularly in patients with CKD or receiving higher doses 6
- Ensure adequate hydration (avoid fluid restriction <30 mL/kg/day) 6
- Re-assess renal function if clinical deterioration occurs
Common Pitfall to Avoid
The "creatinine-blind range" can mask early renal impairment. 3 Do not rely solely on serum creatinine values; always calculate creatinine clearance or GFR, as approximately 20% of hospitalized patients have unrecognized renal impairment. 3 Failure to adjust aciclovir dosing in these patients leads to drug accumulation and increased nephrotoxicity risk. 7, 4