Acyclovir Renal Dose Modification
Acyclovir requires dose reduction in renal impairment based on creatinine clearance, with specific adjustments for oral and intravenous formulations to prevent drug accumulation and nephrotoxicity. 1
Oral Acyclovir Dosing by Renal Function
Standard Dose: 200 mg every 4 hours (5 times daily)
- CrCl >10 mL/min: 200 mg every 4 hours, 5 times daily (no adjustment) 1
- CrCl <10 mL/min: 200 mg every 12 hours 2, 1
- Hemodialysis: 200 mg every 12 hours; administer first daily dose after dialysis 2, 1
Standard Dose: 400 mg every 12 hours
- CrCl >10 mL/min: 400 mg every 12 hours (no adjustment) 1
- CrCl <10 mL/min: 200 mg every 12 hours 1
- Hemodialysis: 200 mg every 12 hours 1
High Dose: 800 mg every 4 hours (for herpes zoster)
- CrCl >25 mL/min: 800 mg every 4 hours, 5 times daily (no adjustment) 1
- CrCl 10-25 mL/min: 800 mg every 8 hours 2, 1
- CrCl <10 mL/min: 800 mg every 12 hours 2, 1
- Hemodialysis: 800 mg every 12 hours 1
Intravenous Acyclovir Dosing by Renal Function
Standard Dose: 5-10 mg/kg IV every 8 hours
- CrCl 25-50 mL/min: 5-10 mg/kg IV every 12 hours 2
- CrCl 10-24 mL/min: 5-10 mg/kg IV every 24 hours 2
- CrCl <10 mL/min: 2.5-5 mg/kg IV every 24 hours 2
- Hemodialysis: 2.5-5 mg/kg IV every 24 hours; administer dose post-dialysis on dialysis days 2
Critical Administration Considerations
Nephrotoxicity Prevention
- Avoid rapid IV bolus administration: Slow infusion over 1 hour is essential to prevent crystal-induced acute renal failure 2, 3
- Ensure adequate hydration: Minimum 1.5 liters of water daily prevents intratubular crystal precipitation 2, 4, 3
- Monitor renal function closely: Check creatinine at baseline and during therapy, especially with high doses 5, 3
Hemodialysis-Specific Guidance
The terminal half-life of acyclovir during hemodialysis is approximately 5 hours, with a 60% decrease in plasma concentrations following 6-hour dialysis 1, 6. The dialysis clearance is 81.8 ± 12.6 mL/min with an extraction coefficient of 0.45 6. Therefore, supplemental dosing after each dialysis session is mandatory 2, 1.
Peritoneal Dialysis
No supplemental dose is required after adjusting the dosing interval 1.
Pharmacokinetic Rationale
Acyclovir is almost entirely eliminated by the kidneys via glomerular filtration and tubular secretion 4. In end-stage renal disease, the terminal plasma half-life increases from 2-3 hours to approximately 19.5 hours 6. Without dose adjustment, drug accumulation occurs, increasing the risk of both nephrotoxicity and neuropsychiatric adverse effects 7.
Common Pitfalls to Avoid
- Water restriction with IV acyclovir: This dramatically increases the risk of crystal-induced renal failure, particularly with high doses 5, 3
- Failure to adjust for pre-existing renal impairment: Even mild renal dysfunction requires dose modification 5, 3
- Bolus IV administration: Always infuse over at least 1 hour to minimize crystalluria risk 2, 3
- Missing post-dialysis supplementation: Hemodialysis removes significant drug, requiring replacement dosing 1, 6