What are the recommended doses of Acyclovir (antiviral medication) for patients with severe or life-threatening viral infections, such as herpes simplex encephalitis, and for those with impaired renal function or less severe infections like mucocutaneous herpes?

Acyclovir Injection Dosing Guidelines

Herpes Simplex Encephalitis (Most Severe Indication)

For herpes simplex encephalitis, administer acyclovir 10 mg/kg IV every 8 hours for 14-21 days in adults and children over 3 months with normal renal function, or 20 mg/kg IV every 8 hours for 21 days in neonates. 1

Critical Timing and Monitoring

• Initiate therapy immediately upon clinical suspicion—mortality decreases to 8% when treatment begins within 4 days of symptom onset, and delays beyond 2 days after hospital admission independently predict poor outcomes 1
• Perform repeat lumbar puncture at 14-21 days to confirm CSF HSV PCR negativity; if PCR remains positive, continue acyclovir with weekly CSF testing until negative 1
• Despite optimal therapy, 18-month mortality remains 28% in adults with approximately 50% of survivors experiencing permanent sequelae 1

Severe Disseminated HSV Disease Requiring Hospitalization

For severe HSV disease with complications such as disseminated infection, encephalitis, pneumonitis, or hepatitis, administer acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical resolution. 2, 3

• The FDA label confirms steady-state peak concentrations of 9.8 mcg/mL at 5 mg/kg and 22.9 mcg/mL at 10 mg/kg dosing 3
• For neonates with disseminated HSV, use 20 mg/kg IV every 8 hours for 21 days 1, 4
• In immunocompromised children, 5 mg/kg IV every 8 hours for 7-14 days is effective for mucocutaneous disease 4

Varicella-Zoster Virus (Chickenpox/Shingles) in Severe Cases

For severe varicella or zoster requiring hospitalization, use acyclovir 10 mg/kg IV every 8 hours (or 500 mg/m² IV every 8 hours for children >1 year). 5, 6

• Continue IV therapy for 5-7 days or until clinical resolution, then may transition to oral therapy 5
• VZV requires higher doses than HSV because it is less sensitive to acyclovir 6

Initial Episode Genital Herpes (Less Severe)

For first episode genital herpes not requiring hospitalization, use acyclovir 5 mg/kg IV every 8 hours for 5 days if parenteral therapy is needed. 2, 3

• Most patients can be managed with oral therapy (200 mg 5 times daily or 400 mg 5 times daily for proctitis) 2, 5

Renal Impairment Dosing Adjustments (Critical Safety Consideration)

Dose adjustment is mandatory in renal impairment based on creatinine clearance to prevent acyclovir crystalluria and nephrotoxicity. 1, 3

Dosing by Creatinine Clearance:

• CrCl >80 mL/min: Standard dosing every 8 hours 3
• CrCl 50-80 mL/min: Standard dose every 12 hours 3
• CrCl 15-50 mL/min: Standard dose every 24 hours 3
• CrCl 0 (anuric): Half-life increases from 2.5 to 19.5 hours; reduce dose to 50% and extend interval to every 24 hours 3

Essential Hydration Requirements:

• Maintain adequate hydration and urine flow throughout treatment—acyclovir maximum solubility is 2.5 mg/mL at 37°C, and exceeding this causes renal tubular crystallization 3
• Never administer as bolus injection; always infuse over 1 hour 3
• Monitor renal function closely, especially with concomitant nephrotoxic drugs 3

Special Populations

Neonates (Birth to 3 Months)

• Clearance is significantly reduced (4.46 mL/min/kg vs 8.44 mL/min/kg in older children) with prolonged half-life (3.8 hours vs 2.36 hours) 3
• Use 20 mg/kg IV every 8 hours for HSV encephalitis or disseminated disease 1, 4

Geriatric Patients

• Plasma concentrations are higher due to age-related renal decline 3
• Dose reduction required based on creatinine clearance 3

Obese Patients

• Use adjusted body weight for dosing calculations in obese patients with normal renal function to avoid both subtherapeutic levels (with ideal body weight) and toxicity (with actual body weight) 7
• In patients with augmented renal clearance, may require up to maximum recommended doses 7

Critical Safety Monitoring

Nephrotoxicity Prevention:

• Nephrotoxicity occurs in 13-21% of patients 7
• Risk factors include dehydration, rapid infusion, pre-existing renal disease, and concomitant nephrotoxic drugs 3

Neurotoxicity Recognition:

• Approximately 1% of patients develop encephalopathic changes (lethargy, confusion, tremors, hallucinations, seizures, or coma) 3
• Use with extreme caution in patients with underlying neurologic abnormalities, significant hypoxia, or electrolyte abnormalities 3

Drug Interactions:

• Probenecid increases acyclovir half-life and AUC by reducing renal clearance 3

Common Pitfalls to Avoid

• Never use topical acyclovir for systemic infections—it is substantially less effective than parenteral or oral therapy 5
• Do not delay treatment pending diagnostic confirmation in suspected encephalitis—early empiric therapy is critical 1
• Do not underdose in encephalitis—use the full 10 mg/kg (not 5 mg/kg) every 8 hours 1
• Do not forget to adjust for renal function—failure to do so significantly increases toxicity risk 3
• Acyclovir does not eradicate latent virus or prevent future recurrences after discontinuation 5