Acyclovir Renal Dose Adjustment
For patients with renal impairment, acyclovir requires significant dose reduction based on creatinine clearance, with intravenous dosing adjusted to 2.5-5 mg/kg every 24 hours for CrCl <10 mL/min and oral dosing reduced to 200 mg every 12 hours for the same degree of impairment. 1
Intravenous Acyclovir Dosing by Renal Function
The Infectious Diseases Society of America provides clear dose adjustments based on creatinine clearance 1:
- CrCl 25-50 mL/min: 5-10 mg/kg IV every 12 hours 1
- CrCl 10-24 mL/min: 5-10 mg/kg IV every 24 hours 1
- CrCl <10 mL/min: 2.5-5 mg/kg IV every 24 hours 1
Hemodialysis Patients
For patients on hemodialysis, administer 2.5-5 mg/kg IV every 24 hours, with the dose given post-dialysis on dialysis days 1. This timing is critical because acyclovir is efficiently removed by hemodialysis, with a dialysis clearance of approximately 81-113 mL/min and an extraction ratio of 0.44-0.45 2, 3. The Centers for Disease Control and Prevention recommends supplemental dosing after each dialysis session 1.
The pharmacokinetic rationale is compelling: in anuric patients, acyclovir's terminal half-life extends from 2-3 hours (normal renal function) to approximately 19.5 hours, with total body clearance reduced to 28.6 mL/min/1.73m² 2. During a 6-hour hemodialysis session, plasma levels can be reduced by approximately 61.5% 3.
Oral Acyclovir Dosing by Renal Function
For patients with CrCl <10 mL/min, the Centers for Disease Control and Prevention recommends reducing oral acyclovir to 200 mg every 12 hours 1. For hemodialysis patients, the first daily dose should be administered after dialysis 1.
Critical Administration Considerations to Prevent Nephrotoxicity
Never administer acyclovir as a rapid IV bolus. The Clinical Infectious Diseases society mandates slow infusion over 1 hour to prevent acyclovir-induced nephrotoxicity 1. This is essential because acyclovir can crystallize in renal tubules, causing acute renal failure—a well-documented complication even in children receiving standard doses 4.
Additional protective measures include 1:
- Ensure adequate hydration with at least 1.5 liters of water daily
- Monitor renal function before and during therapy
- Avoid rapid bolus administration
Important Pharmacokinetic Considerations
The relationship between renal function and acyclovir clearance is direct and predictable 5. Renal excretion via active tubular secretion is the major elimination route, making dose adjustment essential as creatinine clearance declines 5.
While renal impairment dramatically increases systemic acyclovir concentrations, it does not alter the drug's propensity to distribute into cerebrospinal fluid—the CSF-to-plasma ratio remains constant regardless of renal function 6. However, the absolute CSF concentrations are proportionally higher due to elevated plasma levels, which may contribute to neuropsychiatric side effects seen more frequently in renal impairment 6.
Common Pitfalls to Avoid
- Failure to dose post-dialysis: Acyclovir is readily dialyzable; dosing before dialysis results in subtherapeutic levels 2, 3
- Rapid IV administration: This significantly increases nephrotoxicity risk, even with dose adjustment 1
- Inadequate hydration: Insufficient fluid intake promotes intratubular crystallization 1
- Ignoring creatinine clearance: Dose adjustments based solely on serum creatinine without calculating CrCl can lead to overdosing 5