What is the recommended dilution and administration protocol for Acyclovir (antiviral medication) infusion in a patient with severe viral infections and potential Impaired renal function?

Acyclovir Dilution and Administration for Intravenous Infusion

Acyclovir must be diluted before intravenous administration and infused over at least 1 hour to prevent renal tubular damage and acute renal failure. 1

Dilution Requirements

• Acyclovir should never be administered by bolus injection, intramuscularly, subcutaneously, or orally when intravenous therapy is indicated 1
• The maximum solubility of free acyclovir is 2.5 mg/mL at 37°C in water; exceeding this concentration or administering by bolus can cause precipitation of acyclovir crystals in renal tubules, leading to acute renal failure 1
• Standard dilution involves reconstituting the powder and further diluting to achieve appropriate concentrations for infusion 1

Infusion Time and Hydration

• Intravenous infusions must be administered over a minimum of 1 hour to reduce the risk of renal tubular damage 1
• Adequate hydration must accompany acyclovir administration to prevent crystalluria and nephrotoxicity 1
• Approximately 1% of patients receiving intravenous acyclovir develop encephalopathic changes (lethargy, confusion, seizures), particularly those with underlying neurologic abnormalities or renal impairment 1

Dosing Based on Indication and Renal Function

For Severe Viral Encephalitis (HSV):

• Adults with normal renal function: 10 mg/kg IV every 8 hours for 14-21 days 2, 3
• Neonates: 20 mg/kg IV every 8 hours for 21 days 2, 3
• Children 3 months-12 years: 500 mg/m² IV every 8 hours (minimum 21 days recommended) 2
• Children >12 years: 10 mg/kg IV every 8 hours 2

For Severe Mucocutaneous HSV or Disseminated Disease:

• 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution 2

For VZV Pneumonia or Severe Varicella-Zoster:

• 10 mg/kg IV every 8 hours for 7-14 days 4, 5
• Higher doses of 15 mg/kg every 8 hours may be considered if renal function is normal, though most clinicians use 10 mg/kg due to safety concerns 4

Critical Dose Adjustments for Renal Impairment

Dose reduction is mandatory in patients with impaired renal function, as acyclovir is primarily renally excreted (62-91% unchanged drug) 1

• Creatinine clearance >80 mL/min/1.73 m²: Standard dosing (half-life 2.5 hours) 1
• Creatinine clearance 50-80 mL/min/1.73 m²: Reduce dose or extend interval (half-life 3 hours) 1
• Creatinine clearance 15-50 mL/min/1.73 m²: Further dose reduction required (half-life 3.5 hours) 1
• Creatinine clearance <50 mL/min: Reduce dose by 50% 3
• Hemodialysis patients: 200 mg every 12 hours 3
• Anuric patients: Half-life extends to 19.5 hours; significant dose reduction required 1

Monitoring Requirements

• Monitor renal function frequently during therapy, especially at higher doses, as reversible nephropathy can occur in up to 20% of patients, typically after 4 days of IV therapy 2, 1
• Monitor for signs of encephalopathy (confusion, hallucinations, seizures), particularly in patients with renal impairment, neurologic abnormalities, or electrolyte disturbances 1
• Ensure adequate urine flow and hydration throughout treatment 5

Common Pitfalls to Avoid

• Never use fixed doses for serious herpes infections; always calculate based on actual body weight 3
• Do not administer acyclovir too rapidly—infusion times less than 1 hour significantly increase nephrotoxicity risk 1
• Avoid concomitant nephrotoxic drugs, as this substantially increases the risk of renal impairment 1
• Do not assume acyclovir is effective for all viral pneumonias—it has no activity against influenza, RSV, parainfluenza, adenovirus, or CMV 4
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has resulted in death in immunocompromised patients receiving acyclovir 1

Duration of Therapy Considerations

• For proven HSV encephalitis, continue treatment for 14-21 days and perform repeat lumbar puncture to confirm CSF is negative for HSV by PCR 2, 3
• If CSF remains PCR-positive at 14-21 days, continue acyclovir with weekly PCR testing until negative 2
• Children aged 3 months-12 years have higher relapse rates (up to 29%) and should receive a minimum of 21 days of IV acyclovir 2
• Early initiation of treatment (within 4 days of symptom onset) reduces mortality from 28% to 8% in HSV encephalitis 2, 3