What is the recommended dosage of Acyclovir (Antiviral medication) for a patient with Chronic Kidney Disease (CKD) and impaired renal function?

Acyclovir Dosing in Chronic Kidney Disease

Acyclovir requires mandatory dose reduction in patients with CKD based on creatinine clearance, with both the dose and dosing interval adjusted to prevent neurotoxicity and acute kidney injury. 1, 2

Oral Acyclovir Dosing Adjustments

Standard Dosing (Normal Renal Function)

• 200-800 mg orally 3-5 times daily depending on indication (herpes simplex vs. zoster) 1

CKD Dosing by Creatinine Clearance

For CrCl 25-50 mL/min:

• Oral: 200-800 mg 3-5 times daily (no change from normal dosing) 1
• IV: 5-10 mg/kg every 12 hours (extended from every 8 hours) 1

For CrCl 10-24 mL/min:

• Oral: 200-800 mg every 8 hours 1
• IV: 5-10 mg/kg every 24 hours 1

For CrCl <10 mL/min:

• Oral: 200-800 mg every 12 hours 1, 2
• IV: 2.5-5 mg/kg every 24 hours (note the dose reduction by 50%) 1

For patients on hemodialysis:

• IV: 2.5-5 mg/kg every 24 hours, with dosing administered post-dialysis on dialysis days 1
• An additional dose after each dialysis session is required due to 60% drug removal during 6-hour dialysis 2

Intravenous Acyclovir Dosing Adjustments

The FDA label provides specific guidance for high-dose regimens (800 mg every 4 hours equivalent): 2

For CrCl >25 mL/min:

• 800 mg every 4 hours, 5 times daily 2

For CrCl 10-25 mL/min:

• 800 mg every 8 hours 2

For CrCl 0-10 mL/min:

• 800 mg every 12 hours 2

Critical Safety Considerations

Neurotoxicity Risk

• Acyclovir causes dose-dependent neurotoxicity manifesting as confusion, ataxia, altered mental status, and encephalopathy, particularly in renal impairment 3
• The metabolite CMMG (9-[(carboxymethoxy)methyl]guanine) accumulates in renal failure and contributes to neuropsychiatric symptoms 4
• Neurotoxicity is reversible with dose reduction, dialysis, or drug discontinuation 3

Nephrotoxicity Risk

• High-dose acyclovir has known nephrotoxic potential and should be administered under close supervision in CKD patients 1
• Risk factors for acyclovir-induced acute kidney injury include: bolus IV administration, inadequate hydration, pre-existing renal impairment, and excessive dosing 5
• Acyclovir crystallizes in renal tubules when given as rapid bolus or with water restriction 5

Monitoring Requirements

• Calculate creatinine clearance using validated calculators before initiating therapy 6
• Monitor serum creatinine every 2-3 days during treatment, especially in elderly patients whose renal function may fluctuate 6
• Assess for neurological symptoms (confusion, tremor, hallucinations, ataxia) at each clinical encounter 3

Common Prescribing Errors to Avoid

Failure to adjust for renal function is the most common error: 3

• A case report documented severe neurotoxicity in a hemodialysis patient prescribed standard dosing without renal adjustment 3
• Even patients with "normal" serum creatinine may have significantly reduced creatinine clearance, particularly elderly patients with decreased muscle mass 6

Inadequate hydration during IV administration: 5

• Water restriction (≤30 mL/kg/day) combined with IV acyclovir significantly increases nephrotoxicity risk 5
• Ensure adequate hydration (at least 80 mL/kg/day) during IV therapy 5

Practical Algorithm for Dosing

1. Calculate creatinine clearance using Cockcroft-Gault or eGFR 6
2. Select dose reduction tier based on CrCl ranges above 1, 2
3. For hemodialysis patients: Use CrCl <10 mL/min dosing and administer supplemental dose post-dialysis 1, 2
4. For peritoneal dialysis: Adjust dosing interval per CrCl <10 mL/min; no supplemental dose needed 2
5. Reassess renal function every 2-3 days and adjust dosing if creatinine changes 6