Acyclovir Dosing in Hepatic Dysfunction
No dose adjustment of acyclovir is required for patients with hepatic dysfunction alone, as acyclovir is primarily eliminated renally rather than hepatically. 1
Primary Elimination Pathway
- Acyclovir undergoes minimal hepatic metabolism, with the only known urinary metabolite being 9-[(carboxymethoxy)methyl]guanine 1
- The drug is predominantly eliminated unchanged through renal excretion, making hepatic function largely irrelevant to its clearance 1
- Liver dysfunction does not significantly alter acyclovir pharmacokinetics because the drug does not undergo substantial first-pass metabolism 2
Dosing in Isolated Hepatic Dysfunction
Standard acyclovir dosing can be maintained in patients with liver disease without renal impairment. 1
- No specific dose reductions are recommended in FDA labeling for hepatic impairment 1
- The drug's pharmacokinetic profile remains unchanged in cirrhotic patients with preserved renal function 2
Critical Consideration: Concurrent Renal Impairment
The primary concern in hepatic dysfunction is the frequent coexistence of renal impairment (hepatorenal syndrome), which absolutely requires dose adjustment. 3, 1, 4
Oral Acyclovir Adjustments for Renal Impairment:
- CrCl <10 mL/min: Reduce to 200 mg every 12 hours 3
- Hemodialysis patients: Administer first daily dose after dialysis 3
Intravenous Acyclovir Adjustments for Renal Impairment:
- CrCl 25-50 mL/min: 5-10 mg/kg IV every 12 hours 3
- CrCl 10-24 mL/min: 5-10 mg/kg IV every 24 hours 3
- CrCl <10 mL/min: 2.5-5 mg/kg IV every 24 hours 3
- Hemodialysis: 2.5-5 mg/kg IV every 24 hours, administered post-dialysis on dialysis days 3
Essential Safety Measures
Adequate hydration is critical to prevent nephrotoxicity, particularly in cirrhotic patients who may have compromised renal perfusion. 3, 1
- Maintain at least 1.5 liters of water daily 3
- Administer IV acyclovir as a slow infusion over 1 hour, never as a rapid bolus 3, 5
- Rapid IV bolus administration has been associated with transient renal impairment even in patients without pre-existing renal disease 5
Common Pitfall to Avoid
Do not assume hepatic dysfunction requires dose reduction—always assess renal function first. 1, 4
- The half-life and total body clearance of acyclovir are dependent on renal function, not hepatic function 1
- Patients with decompensated cirrhosis frequently develop hepatorenal syndrome, making renal function assessment mandatory before dosing 4
- Geriatric patients with cirrhosis may have age-related renal impairment requiring dose reduction even if hepatic dysfunction is the primary diagnosis 1