What is the recommended intravenous acyclovir dose, dilution, infusion rate, and renal monitoring for an adult with severe herpes simplex virus encephalitis, disseminated varicella‑zoster virus, or herpes‑related keratitis?

How to Administer IV Acyclovir

Administer IV acyclovir by diluting the reconstituted solution to ≤7 mg/mL and infusing over 1 hour at a constant rate, never as a bolus, with mandatory hydration >2 L/day and renal function monitoring before and during therapy. 1

Dosing by Indication

HSV Encephalitis (Adults)

• 10 mg/kg IV every 8 hours for 10 days infused over 1 hour 1
• Maximum dose should not exceed 20 mg/kg every 8 hours for any patient 1

HSV Encephalitis (Pediatric 3 months to 12 years)

• 20 mg/kg IV every 8 hours for 10 days infused over 1 hour 1
• Treatment duration should be 14-21 days in confirmed cases to reduce relapse risk 2

Disseminated VZV in Immunocompromised Patients

• Adults/adolescents ≥12 years: 10 mg/kg IV every 8 hours for 7 days 1
• Children <12 years: 20 mg/kg IV every 8 hours for 7 days 1

Mucocutaneous HSV in Immunocompromised Patients

• Adults/adolescents ≥12 years: 5 mg/kg IV every 8 hours for 7 days 1
• Children <12 years: 10 mg/kg IV every 8 hours for 7 days 1

Preparation and Dilution

Reconstitution

• Dissolve 500 mg vial in 10 mL Sterile Water for Injection (yields 50 mg/mL) 1
• Dissolve 1,000 mg vial in 20 mL Sterile Water for Injection (yields 50 mg/mL) 1
• Never use Bacteriostatic Water containing benzyl alcohol or parabens 1
• Use reconstituted solution within 12 hours 1

Final Dilution for Infusion

• Dilute to ≤7 mg/mL in any standard IV solution (normal saline, D5W, lactated Ringer's) 1
• Higher concentrations (e.g., 10 mg/mL) increase phlebitis risk upon extravasation 1
• Typical adult receives 60-150 mL fluid per dose 1
• Use diluted solution within 24 hours 1

Critical Administration Requirements

Infusion Rate

• Infuse over exactly 1 hour at a constant rate 1
• Never give as rapid IV push or bolus—this dramatically increases nephrotoxicity risk 1, 3
• Never give intramuscularly or subcutaneously 1

Hydration Protocol

• Maintain hydration volume >2 L/day throughout treatment 4
• Patients receiving <2 L/day hydration showed elevated creatinine (1.70 mg/dL) and BUN (22.14 mg/dL) after 3 days 4
• Patients without adequate hydration had creatinine rise to 2.22 mg/dL and eGFR drop to 53 mL/min 4
• Adequate hydration reduces nephropathy risk from 20% to substantially lower rates 2

Renal Function Monitoring

Baseline Assessment

• Measure serum creatinine and calculate creatinine clearance before initiating therapy 1
• Obtain baseline BUN and eGFR 4

During Therapy

• Monitor renal function every 48 hours during treatment 5
• Most renal dysfunction occurs within 48 hours of acyclovir initiation 5
• Nephrotoxicity affects up to 35% of pediatric patients, with 22% showing "risk" level dysfunction and 3.8% progressing to "failure" 5
• Reversible nephropathy typically manifests after 4 days of IV therapy in up to 20% of patients 2

Dose Adjustment for Renal Impairment

Mandatory dose adjustments based on creatinine clearance: 1

• CrCl >50 mL/min: 100% dose every 8 hours
• CrCl 25-50 mL/min: 100% dose every 12 hours
• CrCl 10-25 mL/min: 100% dose every 24 hours
• CrCl 0-10 mL/min: 50% dose every 24 hours

Hemodialysis Patients

• Administer additional dose after each dialysis session 1
• Hemodialysis reduces plasma acyclovir by 60% over 6 hours 1

Special Populations

Obese Patients

• Dose using Ideal Body Weight, not actual body weight 1

Pediatric Considerations

• Avoid doses >15 mg/kg outside the neonatal period to minimize nephrotoxicity 5
• Doses >15 mg/kg increase nephrotoxicity risk 3.8-fold (OR 3.81,95% CI 1.55-9.37) 5
• Children >8 years have 21.5-fold increased risk of renal failure 5

Augmented Renal Clearance (ARC)

• Children with eGFR >250 mL/min/1.73 m² may require 15-20 mg/kg every 6 hours to maintain therapeutic levels 6

Critical Pitfalls to Avoid

Drug Interactions

• Avoid coadministration with ceftriaxone—increases renal failure risk 19.3-fold 5
• Monitor closely if other nephrotoxic drugs are necessary 3

Fluid Restriction Scenarios

• Patients with HSV encephalitis often require fluid restriction for cerebral edema management 3
• This creates competing priorities: balance adequate hydration against ICP management 3
• Consider more frequent renal monitoring in these cases 3

Mechanism of Nephrotoxicity

• Acyclovir crystallizes in renal tubules and collecting ducts when given as bolus or with inadequate hydration 3
• Crystals resolve after treatment cessation, making dysfunction typically reversible 3
• Slow infusion over 1 hour allows time for renal excretion and prevents crystal formation 3

Monitoring for Treatment Failure

HSV Encephalitis Specific

• Consider repeat CSF HSV PCR at days 19-21 of therapy 2
• Do not stop acyclovir until CSF HSV DNA PCR is negative 2
• If CSF remains PCR-positive, continue weekly testing until negative 2

Acyclovir-Resistant HSV

• If clinical failure occurs despite adequate dosing and levels, consider resistance 2
• Switch to foscarnet 40 mg/kg IV every 8 hours for resistant strains 2