Acyclovir Dosing in Warfarin Patients
No dose adjustment of acyclovir is required solely based on concurrent warfarin use, but the INR must be monitored more frequently during acyclovir therapy due to potential drug interaction.
Standard Acyclovir Dosing
The acyclovir dose itself does not need adjustment for warfarin co-administration. Standard dosing remains:
- For HSV encephalitis: 10 mg/kg IV every 8 hours for 14-21 days in adults with normal renal function 1
- For VZV encephalitis: 10-15 mg/kg IV three times daily, though most clinicians use 10 mg/kg 1
- Pediatric dosing (3 months-12 years): 500 mg/m² every 8 hours 1
- Pediatric dosing (>12 years): 10 mg/kg every 8 hours 1
Critical Renal Dose Adjustments
The dose of acyclovir must be reduced in patients with pre-existing renal impairment 1. This is essential because:
- Acyclovir is predominantly renally excreted and can cause crystalluria leading to obstructive nephropathy 1
- Adequate hydration and urine flow must be maintained at standard doses 2
- Mental status monitoring is required as acyclovir can cause neurotoxicity 2
For patients with CrCl 30-49 mL/min, reduce frequency to every 12 hours; for CrCl 10-29 mL/min, reduce to every 24 hours 3.
INR Monitoring Strategy
Increase INR monitoring frequency to every 3-4 days during the first 1-2 weeks of acyclovir therapy, then weekly if stable. While there is no direct guideline addressing acyclovir-warfarin interaction specifically, case reports demonstrate that antiviral agents can affect warfarin metabolism 4. The interaction likely occurs through:
- Competition for CYP2C9 and CYP3A4 isoenzymes 4
- Potential displacement of warfarin from protein binding sites
- Changes in vitamin K metabolism during acute illness
Common Pitfalls to Avoid
Do not assume the acyclovir-warfarin interaction is clinically insignificant. A case report documented a patient stable on warfarin 22.5 mg/week who developed supratherapeutic INR (3.9, then 4.3) after acyclovir initiation for shingles 4. The INR normalized only after discontinuation of concurrent medications.
Do not delay acyclovir initiation to "stabilize" the INR first. For HSV encephalitis, delays beyond 48 hours between hospital admission and acyclovir administration are independent predictors of poor outcome 1. Mortality decreases to 8% if therapy is initiated within 4 days of symptom onset 1.
Practical Management Algorithm
- Obtain baseline INR before starting acyclovir if time permits (do not delay treatment) 1
- Start standard-dose acyclovir immediately based on indication 1
- Check INR on day 3-4 of acyclovir therapy
- Adjust warfarin dose (not acyclovir dose) if INR is outside therapeutic range
- Recheck INR 2-3 days after any warfarin dose adjustment
- Continue weekly INR monitoring once stable during acyclovir course
- Increase INR monitoring again when acyclovir is discontinued, as warfarin requirements may change
Special Considerations
For patients requiring prolonged acyclovir therapy (14-21 days for HSV encephalitis), maintain heightened INR surveillance throughout the treatment course 1. Consider holding 1-2 warfarin doses if INR exceeds 4.0, and administer phytonadione 5 mg if INR exceeds 10 5.
Renal function monitoring is mandatory in all patients receiving IV acyclovir, particularly those on warfarin who may have multiple comorbidities 3. Check BMP if clinical deterioration occurs or new symptoms suggest renal dysfunction 3.