Acyclovir Dose Adjustment in Renal Impairment
Acyclovir requires mandatory dose reduction based on creatinine clearance in patients with renal impairment, with both the dose and dosing interval adjusted according to specific thresholds to prevent nephrotoxicity while maintaining therapeutic efficacy.
Oral Acyclovir Dosing Adjustments
The FDA-approved dosing adjustments for oral acyclovir vary by indication and severity of renal impairment 1:
For 200 mg every 4 hours regimen:
- CrCl >10 mL/min: 200 mg every 4 hours (5 times daily) - no adjustment needed 1
- CrCl 0-10 mL/min: 200 mg every 12 hours 1
For 400 mg every 12 hours regimen:
- CrCl >10 mL/min: 400 mg every 12 hours - no adjustment needed 1
- CrCl 0-10 mL/min: 200 mg every 12 hours 1
For 800 mg every 4 hours regimen (herpes zoster):
- CrCl >25 mL/min: 800 mg every 4 hours (5 times daily) - no adjustment needed 1
- CrCl 10-25 mL/min: 800 mg every 8 hours 1
- CrCl 0-10 mL/min: 800 mg every 12 hours 1
For patients with CrCl <10 mL/min not on dialysis, the CDC recommends 200 mg every 12 hours as a simplified approach 2.
Intravenous Acyclovir Dosing Adjustments
The Infectious Diseases Society of America provides clear guidance for IV acyclovir dose modifications 2, 3:
- CrCl 25-50 mL/min: 5-10 mg/kg IV every 12 hours 2, 3
- CrCl 10-24 mL/min: 5-10 mg/kg IV every 24 hours 2, 3
- CrCl <10 mL/min: 2.5-5 mg/kg IV every 24 hours 2, 3
The rationale for these adjustments is that acyclovir is almost entirely eliminated by the kidneys, with terminal half-life increasing from 2-3 hours in normal renal function to approximately 19.5 hours in anuric patients 4, 5.
Hemodialysis Considerations
Acyclovir is readily dialyzable with a dialysis clearance of approximately 82 mL/min and an extraction coefficient of 0.45, resulting in a 60% decrease in plasma concentrations during a 6-hour dialysis session 1, 4.
Dosing strategy for hemodialysis patients:
- Oral: Administer an additional 200 mg dose after each dialysis session 2, 1
- IV: 2.5-5 mg/kg every 24 hours, administered post-dialysis on dialysis days 2, 3
- The terminal half-life during hemodialysis decreases to approximately 5.7 hours 4
Peritoneal dialysis:
- No supplemental dosing is required after adjusting the dosing interval 1
Critical Safety Measures to Prevent Nephrotoxicity
Never administer IV acyclovir as a rapid bolus - this is a common and dangerous pitfall 2, 3. The following precautions are essential:
- Infuse IV acyclovir slowly over at least 1 hour to prevent crystallization in renal tubules 2, 3
- Ensure adequate hydration with at least 1.5 liters of water daily 2, 3
- Avoid concomitant nephrotoxic drugs when possible 3
- Monitor renal function before and during therapy, as acyclovir itself can worsen renal function 3, 6
Pharmacokinetic Rationale
Renal impairment significantly affects acyclovir disposition 7, 5:
- Total body clearance is markedly reduced in anuric patients, being directly dependent on creatinine clearance 5
- Higher systemic concentrations in renal impairment lead to proportionally higher CSF concentrations, though CSF penetration ratios remain constant at approximately 50% of plasma levels 7, 5
- Active tubular secretion is a major component of acyclovir elimination, which is compromised in renal dysfunction 5
Common Pitfalls to Avoid
- Failure to calculate creatinine clearance: Serum creatinine alone is insufficient; use the Cockcroft-Gault equation to estimate CrCl 6
- Dosing errors are extremely common: Studies show that 51-58% of prescriptions requiring dose adjustment in renal impairment are inappropriate 8
- Forgetting post-dialysis supplementation: This leads to subtherapeutic levels and treatment failure 1, 4
- Rapid IV administration: This is the most critical error leading to acute nephrotoxicity 2, 3