What is the maximum dose for intravenous (IV) acyclovir?

Maximum Dose for Intravenous Acyclovir

The maximum dose of IV acyclovir is 10 mg/kg every 8 hours for most severe HSV infections in children and adults, though specific conditions may require higher dosing up to 20 mg/kg every 8 hours for neonatal HSV CNS disease. 1

Standard Maximum Dosing by Indication

For CNS and Disseminated HSV Disease (Non-Neonatal)

• 10 mg/kg IV every 8 hours (three times daily) for 21 days is the recommended maximum dose for children with CNS or disseminated HSV disease outside the neonatal period 1
• Some experts use body surface area dosing of 500 mg/m² IV every 8 hours as an alternative approach in children over 1 year of age 1

For Neonatal HSV Infections

• Higher doses of 20 mg/kg IV every 8 hours are typically used for neonates with HSV CNS disease, representing the highest recommended dose 2
• Standard neonatal dosing for disseminated disease is 20 mg/kg/dose IV every 8 hours 3, 4

For Moderate to Severe Mucocutaneous Disease

• 5-10 mg/kg IV every 8 hours until lesions begin to regress, then transition to oral therapy 1
• This represents the lower end of the dosing spectrum but is appropriate for less severe presentations

For Severe HSV in Immunocompromised Patients

• 5 mg/kg IV every 8 hours may be required for severe cases in HIV-infected or other immunocompromised patients 1
• This is notably lower than pediatric dosing but reflects adult guideline recommendations

Critical Dosing Considerations

Renal Function Adjustments

• The standard maximum doses assume normal renal function (eGFR ≤250 mL/min/1.73 m²) 5
• Dose reduction is mandatory in renal impairment to prevent nephrotoxicity and neurotoxicity 6
• Monitor creatinine levels, as elevated creatinine occurs in approximately 2% of treated infants 4

Augmented Renal Clearance

• Children with augmented renal clearance (eGFR >250 mL/min/1.73 m²) may require higher doses of 15-20 mg/kg every 6 hours to maintain therapeutic concentrations 5
• This represents a clinical scenario where exceeding standard maximum doses may be necessary

Body Weight Considerations

• Use actual body weight for normal weight patients 6
• Use adjusted body weight for obese patients to avoid both subtherapeutic dosing and toxicity 6
• Maximum single dose typically capped at the adult equivalent when using weight-based dosing

Safety Profile at Maximum Doses

Common Adverse Events

• Thrombocytopenia occurs in 25% of infants on high-dose therapy (60 mg/kg/day total) 4
• Hypotension and seizures each occur in approximately 9% of treated infants 4
• Overall, 45% of infants experience at least one adverse event, though most are not severe 4

Serious Toxicities

• Nephrotoxicity prevalence ranges from 13-21% with standard dosing 6
• Neurotoxicity can occur but prevalence is not well-defined 6
• Renal failure requiring dialysis is rare with appropriate dosing and hydration 4

Key Clinical Pitfalls

Inadequate Hydration

• Ensure adequate hydration throughout treatment to minimize nephrotoxicity risk 2, 7
• This is particularly critical at maximum doses

Premature Discontinuation in CNS Disease

• For neonatal CNS disease, do not stop acyclovir until repeat CSF HSV DNA PCR is negative at days 19-21 of therapy 1
• This may require extending treatment beyond the standard 21-day course

Therapeutic Drug Monitoring

• Consider therapeutic drug monitoring to maintain trough concentrations above 0.56 mg/L for HSV (or 1.125 mg/L for VZV) while keeping peak concentrations below 25 mg/L 5
• Target serum concentrations of at least 3 mg/L to ensure adequate CSF penetration (≥1 mg/L) 3