What are the recommended oral and intravenous acyclovir doses for herpes zoster in adults, the dose adjustments for impaired renal function, the dosing for children older than two years, and alternative antivirals if acyclovir is contraindicated?

Acyclovir Dosage for Herpes Zoster (Shingles)

For immunocompetent adults with herpes zoster, the standard oral acyclovir dose is 800 mg five times daily for 7 days, initiated within 72 hours of rash onset. 1, 2

Oral Dosing for Adults

Immunocompetent Patients

• 800 mg orally 5 times daily for 7 days is the FDA-approved regimen 2
• Treatment must be started within 72 hours of rash onset for optimal efficacy 2
• This dosing achieves adequate antiviral concentrations while maintaining the favorable safety profile of acyclovir 3

Immunocompromised Patients (Including HIV)

• 800 mg orally 5 times daily for 7-10 days for standard cases 1
• Some experts recommend dosing based on body surface area: 500 mg/m² every 8 hours 4, 1
• For severe or disseminated disease, intravenous therapy is preferred over oral treatment 1

Intravenous Dosing for Adults

Severe or Disseminated Disease

• 10 mg/kg IV every 8 hours for 7-10 days for immunocompromised patients with severe disease 1, 5, 6
• Alternative dosing: 500 mg/m² IV every 8 hours 4, 1, 5
• Adequate hydration must be maintained to prevent nephrotoxicity 2, 6

Pediatric Dosing (Children >2 Years)

Oral Therapy

• 20 mg/kg orally (maximum 800 mg/dose) 4 times daily for 7-10 days for HIV-infected children 4, 1
• This achieves plasma concentrations comparable to adult therapeutic levels 5

Intravenous Therapy

• 10 mg/kg IV every 8 hours for 10-14 days for severe disease in HIV-infected children 4, 1
• Alternative: 500 mg/m² IV every 8 hours for children aged >1 year 4
• Neonates and infants <3 months require different pharmacokinetic considerations due to immature renal function 5

Renal Dose Adjustments

Dosage reduction is mandatory in patients with impaired renal function to prevent accumulation and CNS toxicity. 2, 5

Creatinine Clearance-Based Adjustments

• CrCl >80 mL/min: No adjustment needed (half-life 2.5 hours) 5
• CrCl 50-80 mL/min: Reduce frequency or dose (half-life 3 hours) 5
• CrCl 15-50 mL/min: Further dose reduction required (half-life 3.5 hours) 5
• CrCl 0 (anuric): Significant reduction necessary (half-life 19.5 hours) 5

Important Renal Considerations

• Maintain adequate hydration throughout treatment 2, 6
• Monitor mental status for CNS symptoms (confusion, hallucinations) 2
• Avoid coadministration with other nephrotoxic agents 2
• Probenecid increases acyclovir half-life and reduces renal clearance 5

Alternative Antivirals

When Acyclovir is Contraindicated or Inconvenient

Valacyclovir 1000 mg three times daily for 7 days offers superior convenience with comparable or better efficacy. 3

• Valacyclovir provides 3-5 fold higher bioavailability than acyclovir 3
• Significantly accelerates resolution of zoster-associated pain (median 38 days vs 51 days with acyclovir, p=0.001) 3
• Reduces duration of postherpetic neuralgia and proportion of patients with pain at 6 months (19.3% vs 25.7%) 3

Famciclovir 500 mg three times daily for 7-10 days is equally effective with better dosing convenience. 4, 1, 7

• FDA-approved at 500 mg every 8 hours for 7 days 7
• Comparable efficacy to acyclovir for cutaneous healing 8
• Longer intracellular half-life (7 hours vs 1 hour for acyclovir) allows less frequent dosing 8

Acyclovir-Resistant Cases

Foscarnet 40-60 mg/kg IV every 8 hours for 7-10 days is the treatment of choice for acyclovir-resistant varicella zoster virus. 4, 1

• Resistance occurs primarily in immunocompromised patients 4, 1
• Higher doses of oral antivirals may be attempted before switching to foscarnet 4

Critical Clinical Caveats

Timing of Initiation

• No data support efficacy when treatment is started >72 hours after rash onset 2
• Early initiation is essential for maximum benefit in preventing complications 2, 6

Special Populations

• Geriatric patients: Higher plasma concentrations due to age-related renal decline; dose adjustment often necessary 5
• Pregnant patients: Acyclovir does not impair fertility, but high-dose animal studies showed decreased implantation efficacy 2

Monitoring Requirements

• Assess renal function before initiating therapy 2, 5
• Monitor mental status, especially in elderly or renally impaired patients 2
• Ensure adequate urine output throughout treatment 6

Limitations

• Acyclovir does not eradicate latent virus or prevent future recurrences 2
• Neither acyclovir nor vidarabine has been clearly proven to prevent postherpetic neuralgia 6
• In young healthy adults, the cost-benefit ratio may not justify treatment given the benign disease course 9