What are the recommended acyclovir dosing regimens for typical adult and pediatric patients with normal renal function, and how should the dose be adjusted for renal impairment?

Acyclovir Dosing Guidelines

Standard Adult Dosing (Normal Renal Function)

For serious herpes simplex virus (HSV) infections including encephalitis, adults with normal renal function should receive acyclovir 10 mg/kg IV every 8 hours for 14-21 days. 1, 2, 3

• HSV encephalitis: 10 mg/kg IV every 8 hours for 14-21 days 1, 2, 3
• HSV meningitis: 10 mg/kg IV every 8 hours for 14-21 days 2
• Mucocutaneous HSV in immunocompromised patients: 5 mg/kg IV every 8 hours for 7-14 days 3
• Initial genital herpes (severe cases): 5 mg/kg IV every 8 hours for 5 days 3
• Varicella-zoster virus (VZV) encephalitis: 10-15 mg/kg IV every 8 hours for 10-14 days 4

Oral Dosing for Less Severe Infections

• HSV prophylaxis: 200 mg orally three times daily or 400 mg every 12 hours 4
• Chickenpox (mild cases): 20 mg/kg orally (max 800 mg/dose) four times daily for 7-10 days 4

Pediatric Dosing (Normal Renal Function)

Neonates with HSV encephalitis require higher doses of 20 mg/kg IV every 8 hours for 21 days to achieve adequate CNS penetration and reduce mortality. 1, 2

• Neonates (birth to 3 months) with HSV CNS disease: 20 mg/kg IV every 8 hours for 21 days 4, 1, 2
• Children 3 months to 12 years with HSV encephalitis: 500 mg/m² IV every 8 hours (or 20 mg/kg IV every 8 hours) for minimum 21 days 4, 2, 3
• Adolescents >12 years: 10 mg/kg IV every 8 hours for 14-21 days 2
• Chickenpox (children with normal immunity): 20 mg/kg orally (max 800 mg/dose) four times daily for 7-10 days 4

Critical Pediatric Considerations

• Children 3 months to 12 years require a minimum 21-day course before considering treatment cessation, as shorter courses are associated with relapse rates of 26-29% 2, 5
• Dosing based on body surface area (500 mg/m²) achieves similar plasma concentrations to weight-based dosing (20 mg/kg) in children 3, 5

Renal Dose Adjustments

Acyclovir dosing must be reduced in renal impairment because 62-91% of the drug is renally excreted, and failure to adjust can lead to nephrotoxicity and neurotoxicity. 4, 3

IV Acyclovir Dose Adjustments

Creatinine Clearance	Standard Dose Adjustment
>50 mL/min	No adjustment: 5-10 mg/kg IV every 8 hours [4]
25-50 mL/min	5-10 mg/kg IV every 12 hours [4]
10-24 mL/min	5-10 mg/kg IV every 24 hours [4]
<10 mL/min	2.5-5 mg/kg IV every 24 hours [4]
Hemodialysis	2.5-5 mg/kg IV every 24 hours; administer dose after dialysis [4]

Oral Acyclovir Dose Adjustments

Creatinine Clearance	Oral Dose Adjustment
>50 mL/min	No adjustment: 200-800 mg orally 3-5 times daily [4]
<10 mL/min	200 mg every 12 hours [4]
Hemodialysis	200 mg every 12 hours; give first daily dose after dialysis [4]

Critical Administration Guidelines

Infusion Requirements

• Administer IV acyclovir as a constant-rate infusion over at least 1 hour to prevent crystalluria and obstructive nephropathy 3
• Never give as IV bolus—bolus administration significantly increases risk of nephrotoxicity 6
• Maintain adequate hydration throughout treatment (crystalluria occurs in up to 20% of patients after 4 days of IV therapy) 2, 3

Monitoring Requirements

• Monitor renal function (serum creatinine) throughout treatment, especially after 4 days when nephrotoxicity typically manifests 2, 3
• For CNS infections, consider repeat CSF PCR at 14-21 days in patients without appropriate clinical response 1, 2
• If CSF PCR remains positive at end of treatment, continue antiviral therapy 1, 2

Common Pitfalls to Avoid

Never Use Oral Acyclovir for Acute CNS Infections

Oral acyclovir does not achieve adequate CSF concentrations for meningitis or encephalitis—IV therapy is mandatory for all CNS herpes infections. 2

• CSF concentrations are approximately 50% of plasma values with IV administration 3
• Oral bioavailability is only 12-20%, insufficient for CNS disease 3, 7, 8

Do Not Use Fixed Doses

Calculate acyclovir doses based on actual body weight (mg/kg), not fixed doses, to ensure adequate drug exposure while minimizing toxicity. 1

• Steady-state peak concentrations with 5 mg/kg every 8 hours: 9.8 mcg/mL (range 5.5-13.8) 3
• Steady-state peak concentrations with 10 mg/kg every 8 hours: 22.9 mcg/mL (range 14.1-44.1) 3

Do Not Stop Treatment Prematurely

• Original 10-day regimens for HSV encephalitis led to relapse rates of 26-29% in children 2
• Current guidelines mandate 14-21 days for adults and minimum 21 days for children <12 years 1, 2
• Early treatment initiation (within 4 days of symptom onset) reduces mortality from 28% to 8% 1, 2

Special Populations

Immunocompromised Patients

• May require prolonged courses beyond 21 days if CSF PCR remains positive 2
• For HIV-infected patients with severe HSV disease: 5 mg/kg IV every 8 hours 2
• If acyclovir resistance suspected (persistent lesions despite therapy), switch to foscarnet 40 mg/kg IV every 8 hours 2

Geriatric Patients

• Acyclovir plasma concentrations are higher in elderly patients due to age-related decline in renal function 3
• Dose reduction required based on creatinine clearance, not age alone 3
• More vigilant monitoring for nephrotoxicity and neurotoxicity needed 3

Neonates

• Clearance in neonates is approximately one-third of adult values 3, 7
• Elimination half-life decreases sharply during first month of life from 10-15 hours to 2.5 hours 8
• Higher doses (20 mg/kg vs 10 mg/kg) required due to immature renal function and worse outcomes 1, 2

Adverse Effects

Nephrotoxicity (Most Common)

• Occurs in up to 20% of patients after approximately 4 days of IV therapy 2, 3
• Manifests as crystalluria, elevated serum creatinine, or obstructive nephropathy 4, 2, 6
• Prevention: Maintain adequate hydration, slow infusion over ≥1 hour, monitor renal function 2, 3
• Reversible with dose adjustment or discontinuation 2

Rare but Serious

• Neurotoxicity (encephalopathy, confusion, tremors)—more common with renal impairment 3, 9
• Hepatitis, bone marrow suppression—rare but require monitoring 2
• Infusion site inflammation with IV administration 6