What is the recommended dosing and dilution of Acyclovir (antiviral medication) injection?

Acyclovir Injection Dosing and Dilution

Standard Dosing Regimens

Acyclovir IV dosing varies by indication and age, with 10 mg/kg every 8 hours being the most common dose for serious HSV infections in adults and children >12 years, while younger children typically receive 500 mg/m² every 8 hours. 1, 2

By Indication and Age Group

HSV Encephalitis/CNS Disease:

• Children 3 months to 12 years: 500 mg/m² IV every 8 hours for 14-21 days 1
• Adolescents >12 years and adults: 10 mg/kg IV every 8 hours for 14-21 days 1, 3, 2
• Neonates (CNS disease): 20 mg/kg IV every 8 hours for 21 days 1

Disseminated HSV or Life-Threatening Infections (including hepatitis):

• Children outside neonatal period: 10 mg/kg IV every 8 hours for 21 days 1
• Adults: 5-10 mg/kg IV every 8 hours until clinical resolution 4, 2
• The higher end of dosing (10 mg/kg) is appropriate for CNS or disseminated disease 4

Mucocutaneous HSV (moderate to severe):

• Children: 5-10 mg/kg IV every 8 hours until lesions regress, then switch to oral 1
• Immunocompromised patients: 5 mg/kg IV every 8 hours for 7-14 days 5

Varicella (severe/immunocompromised):

• Children >1 year: Some experts use 500 mg/m² IV every 8 hours instead of weight-based dosing 1
• Standard weight-based: 10 mg/kg IV every 8 hours 1

Special Populations

Neonates (<3 months):

• Clearance is approximately one-third of adult values 6
• Dosing: 10-20 mg/kg IV every 8 hours depending on indication 1, 2
• For CNS disease specifically: 20 mg/kg every 8 hours for 21 days 1

Augmented Renal Clearance (eGFR >250 mL/min/1.73 m²):

• May require 15-20 mg/kg every 6 hours to maintain therapeutic levels 7
• Standard dosing often inadequate in this population 7

Renal Impairment:

• CrCl 50-80 mL/min: Reduce frequency or dose 2
• CrCl 15-50 mL/min: Significant dose reduction required 2
• CrCl 0 (anuric): Half-life increases from 2.5 hours to 19.5 hours; clearance drops to 29 mL/min/1.73 m² 2
• Dose adjustments mandatory based on creatinine clearance 1, 2

Dilution and Administration

Acyclovir must be diluted before infusion and administered over at least 1 hour to prevent nephrotoxicity. 2

Reconstitution:

• 500 mg vial: Add 10 mL Sterile Water for Injection → final concentration 50 mg/mL 2
• 1000 mg vial: Add 20 mL Sterile Water for Injection → final concentration 50 mg/mL 2
• Reconstituted solution pH is approximately 11 2

Further Dilution (Mandatory):

• Must be further diluted in appropriate IV solution before infusion 2
• Do not administer as bolus or undiluted 2
• Standard practice: dilute to concentration ≤7 mg/mL for peripheral administration 2

Infusion Guidelines:

• Standard infusion time: 1 hour 2
• For doses >1 mg/kg or patients with azotemia/hyperkalemia: Infuse over 3-6 hours 1
• Rapid infusion increases risk of crystalluria and renal toxicity 2

Critical Monitoring and Precautions

Nephrotoxicity Risk:

• Occurs in up to 20% of patients after 4 days of IV therapy 3
• Monitor creatinine throughout treatment 3, 2
• Maintain adequate hydration to reduce risk 3, 2
• Risk exacerbated by concomitant nephrotoxic drugs 1
• Hydration with 0.9% saline over 30 minutes before infusion may ameliorate nephrotoxicity 1

Common Pitfalls to Avoid:

• Never use oral acyclovir for life-threatening infections - IV administration is essential 4
• Do not underdose children with augmented renal clearance - they may need higher or more frequent dosing 7
• Do not skip dose adjustments in renal impairment - acyclovir is 62-91% renally excreted 3, 2
• Do not infuse too rapidly - increases crystalluria risk 2

Therapeutic Drug Monitoring:

• Target trough concentrations: >0.56 mg/L for HSV, >1.125 mg/L for VZV 7, 8
• Target peak concentrations: <25 mg/L to avoid toxicity 7
• Consider TDM in patients with renal dysfunction, augmented clearance, or inadequate clinical response 7

Treatment Duration Considerations:

• HSV encephalitis: 14-21 days 1, 3
• Neonatal HSV CNS disease: Full 21 days; repeat CSF HSV PCR at days 19-21 and do not stop until negative 1
• Disseminated HSV: Until clinical resolution 4
• Mucocutaneous HSV: 7-14 days or until lesions heal 1, 5

Resistance Considerations:

• If lesions persist despite appropriate therapy, consider acyclovir resistance 4, 3
• Alternative: Foscarnet 40 mg/kg IV every 8 hours 1, 9, 3

Pharmacokinetic Principles

Key Parameters:

• Half-life in normal renal function: 2.5 hours 2, 10
• Volume of distribution: ~7.36 L (approximately 1 L/kg) 8
• Clearance: 327 mL/min/1.73 m² in adults with normal renal function 10
• CSF concentrations: approximately 50% of plasma levels 2, 10
• Plasma protein binding: 9-33% (low, minimal drug interaction risk) 2, 10
• Bioavailability (oral): approximately 20% 6

Dose Proportionality:

• Linear pharmacokinetics observed from 0.5 to 15 mg/kg 2, 10
• Proportionality between dose and plasma levels after single or multiple doses 2
• Similar plasma levels achieved in adults and children >1 year when dosed by body surface area 10