What are the recommended oral and intravenous acyclovir dosing regimens for immunocompetent adults with uncomplicated herpes simplex virus (HSV) or varicella‑zoster virus (VZV) infections, including renal dose adjustments, adverse effects, contraindications, and alternative agents?

Acyclovir Dosing and Management for HSV and VZV Infections

Oral Acyclovir Dosing Regimens

For uncomplicated herpes zoster (shingles) in immunocompetent adults, oral acyclovir 800 mg five times daily for 7-10 days is the standard regimen, with treatment continuing until all lesions have completely scabbed. 1, 2

HSV Infections

• Initial or recurrent genital herpes: Acyclovir 400 mg orally 3-5 times daily for 7-10 days until all lesions heal 3, 4
• Suppressive therapy for frequent recurrences: Acyclovir 400 mg twice daily continuously 1, 5
• Mucocutaneous HSV in immunocompromised patients: Acyclovir 400 mg orally 3-5 times daily, continuing until complete healing (often requires >10 days) 3

VZV Infections

• Uncomplicated herpes zoster: Acyclovir 800 mg orally five times daily for 7-10 days, continuing until all lesions scab 1, 2
• Primary varicella (chickenpox): Acyclovir 800 mg five times daily 6, 2
• Post-exposure prophylaxis (if >96 hours after exposure or immunoglobulin unavailable): Acyclovir for 7 days beginning 7-10 days after exposure 6

Intravenous Acyclovir Dosing Regimens

For disseminated or invasive herpes zoster, systemic HSV, or severe VZV infections in immunocompromised patients, intravenous acyclovir 10 mg/kg every 8 hours is the treatment of choice. 1, 2

Specific IV Indications and Dosing

• Disseminated/invasive herpes zoster: 10 mg/kg IV every 8 hours until all lesions scab 1
• Systemic HSV infection: 5-10 mg/kg IV every 8 hours for 14-21 days total (switch to oral after clinical response) 6, 3
• Herpes simplex encephalitis: 10 mg/kg IV every 8 hours 5, 4
• Severe VZV in immunocompromised hosts: 10 mg/kg IV every 8 hours, minimum 7-10 days until clinical resolution 6, 1
• Varicella-zoster in immunocompromised patients: 500 mg/m² or 10 mg/kg IV every 8 hours 2

Renal Dose Adjustments

Acyclovir dosing must be adjusted for renal impairment to prevent crystalluria and acute renal failure. 1, 7

Adjustment Algorithm by Creatinine Clearance

• CrCl ≥50 mL/min: No adjustment needed for standard dosing 1
• CrCl 25-50 mL/min: Administer standard dose every 12 hours 7
• CrCl 10-25 mL/min: Administer standard dose every 24 hours 7
• CrCl <10 mL/min: Administer 50% of standard dose every 24 hours 7
• Hemodialysis patients: Administer dose after dialysis session 4

Critical Monitoring Requirements

• Assess baseline renal function before initiating therapy 1
• Monitor serum creatinine once or twice weekly during IV therapy 1
• Maintain adequate hydration and urine flow, especially with high-dose IV therapy 2
• Infuse IV acyclovir slowly over 1 hour (never as bolus) to prevent crystalluria 7

Adverse Effects and Contraindications

Common Adverse Effects

• Crystalluria and elevated serum creatinine: Most important adverse effect, related to rapid IV bolus administration 7
• Infusion site inflammation: Occurs with IV administration 7
• Transient serum creatinine elevations: Seen during high-dose IV use, typically reversible 4
• Mental status changes: Monitor neurological status, especially at high doses 2

Rare but Serious Complications

• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: Monitor in immunocompromised patients receiving high-dose therapy 1
• Acute renal failure: Prevented by slow infusion, adequate hydration, and dose adjustment 1, 7

Contraindications and Precautions

• Hypersensitivity to acyclovir or valacyclovir: Use foscarnet 40 mg/kg IV every 8 hours as alternative 3, 8
• Severe renal impairment without dose adjustment: Mandatory adjustment required 7
• Dehydration: Ensure adequate hydration before and during therapy 2

Alternative Agents

First-Line Alternatives (Cross-Reactive with Acyclovir)

• Valacyclovir: Superior bioavailability (3-5 times higher than acyclovir), dosed 1000 mg three times daily for herpes zoster 1, 5
• Famciclovir: Better bioavailability, dosed 500 mg three times daily for herpes zoster 1

Note: All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. 3, 8

For Acyclovir-Resistant or Allergic Patients

• Foscarnet: 40 mg/kg IV every 8 hours until clinical resolution (first-line for resistance/allergy) 3, 8
• Topical cidofovir gel 1%: Once daily for 5 consecutive days (for localized lesions only) 1, 8

Critical Clinical Pitfalls to Avoid

Treatment Duration Errors

• Never stop treatment at exactly 7 days if lesions are still active or forming 1, 3
• Immunocompromised patients develop lesions over 7-14 days and require extended therapy beyond standard 7-10 day courses 6, 1
• The endpoint is complete scabbing/healing of all lesions, not calendar days 1

Route Selection Errors

• Topical acyclovir is substantially less effective than systemic therapy and should not be used for HSV or VZV 1, 3
• Oral therapy should be reserved for mild cases in patients with transient immunosuppression or to complete IV therapy after clinical response 6

Immunosuppression Management

• Temporarily reduce or discontinue immunosuppressive medications in disseminated/invasive disease 6, 1, 3
• Do not restart immunosuppression until lesions have crusted and patient shows clinical improvement on antivirals 1

Resistance Recognition

• If lesions fail to improve within 7-10 days despite adequate dosing, suspect acyclovir resistance and obtain viral culture with susceptibility testing 1
• Resistance is rare in immunocompetent patients but occurs more frequently in immunocompromised patients on prolonged suppressive therapy 1, 4