What is the recommended dosage and treatment duration of acyclovir for a patient with a viral infection, such as genital herpes or shingles, and potential impaired renal function?

Acyclovir Dosing and Treatment Duration

For genital herpes or shingles with normal renal function, use acyclovir 800 mg orally 5 times daily for 7-10 days for shingles, or 400 mg orally 3 times daily for 5 days for recurrent genital herpes; dose adjustments are mandatory in renal impairment to prevent acute renal failure. 1

Herpes Simplex Virus (HSV) Infections

Recurrent Genital or Oral HSV

• Episodic treatment: Acyclovir 400 mg orally 3 times daily for 5 days, or 800 mg orally twice daily for 5 days 1
• Treatment is most effective when initiated at the first sign of prodrome or lesion appearance 1
• A 2-day regimen (800 mg orally 3 times daily) has been shown to significantly reduce lesion duration and viral shedding, offering a convenient alternative 2

First-Episode Genital HSV

• Acyclovir 200 mg orally 5 times daily for 10 days shortens viral shedding (median 2 days vs 9 days with placebo), accelerates healing (12 days vs 16 days), and reduces pain duration (5 days vs 7 days) 3
• Higher doses may be considered for severe presentations 1

Suppressive Therapy for Frequent Recurrences

• Standard dose: Acyclovir 400 mg orally twice daily reduces recurrence frequency by ≥75% in patients with ≥6 episodes per year 1, 4
• Alternative regimens include 200 mg orally 3-5 times daily, though twice-daily dosing improves adherence 4
• After 12 months of continuous suppression, discontinue therapy to reassess recurrence rate 4
• For HIV-infected or immunocompromised patients: Higher doses (400 mg orally 3-5 times daily) are often necessary 5, 4

Severe HSV Disease Requiring Hospitalization

• Acyclovir 5-10 mg/kg IV every 8 hours for 5-7 days or until clinical improvement 1
• For CNS involvement (encephalitis): Acyclovir 10 mg/kg IV every 8 hours for 14-21 days 5
• Predictors of poor outcome include age >30 years, Glasgow coma score <6, and delay >4 days before starting treatment 5
• Consider obtaining CSF PCR at end of therapy; if positive despite treatment, continue antiviral therapy 5

Varicella-Zoster Virus (VZV) Infections

Uncomplicated Herpes Zoster (Shingles)

• Acyclovir 800 mg orally 5 times daily for 7-10 days until all lesions have completely scabbed 1, 6
• Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain and preventing postherpetic neuralgia 6
• Do not discontinue at exactly 7 days if lesions are still forming or have not scabbed—continue until complete crusting occurs 6

Disseminated or Severe Herpes Zoster

• Acyclovir 10 mg/kg IV every 8 hours for minimum 7-10 days and until all lesions have scabbed 6
• Indications for IV therapy include:
  • Multi-dermatomal involvement or visceral disease 6
  • Immunocompromised status (HIV, chemotherapy, transplant recipients) 6
  • CNS complications or complicated ocular disease 6
  • Facial involvement with risk of cranial nerve complications 6

Immunocompromised Patients with Uncomplicated Zoster

• Higher oral doses may be used: acyclovir 400 mg orally 3-5 times daily until clinical resolution 6
• However, IV therapy is generally preferred due to high risk of dissemination 6
• Consider temporary reduction in immunosuppressive medications during treatment 6

Renal Dose Adjustments

Renal function monitoring and dose adjustment are critical to prevent acute renal failure, particularly with IV acyclovir. 5, 6

• Monitor renal function at initiation and once or twice weekly during IV treatment 5, 6
• Ensure adequate hydration, as acyclovir is primarily renally excreted 1
• Specific dose adjustments based on creatinine clearance are mandatory but vary by indication and route 6
• For oral therapy in patients with substantial renal impairment, dose reduction is necessary 5

Treatment Failure and Acyclovir Resistance

• Suspect resistance if lesions do not begin to resolve within 7-10 days of therapy 5, 6
• Obtain viral culture with susceptibility testing to confirm resistance 5
• For confirmed acyclovir-resistant HSV or VZV: Foscarnet 40 mg/kg IV every 8 hours (or 60 mg/kg IV every 12 hours) until clinical resolution 5, 1, 6
• All acyclovir-resistant strains are also resistant to valacyclovir, and most to famciclovir 6
• Topical alternatives (cidofovir, trifluridine, imiquimod) may be used for external lesions but require prolonged application (21-28 days) 5

Critical Monitoring and Safety Considerations

Adverse Effects

• Common: Nausea, headache 5
• Serious: Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported with high-dose valacyclovir (8 g/day) in HIV-infected patients—avoid this dose 5, 4
• Neutropenia is the most common toxicity in children receiving acyclovir 1

Laboratory Monitoring

• No routine monitoring needed for episodic or suppressive oral therapy in patients with normal renal function 5
• For high-dose IV acyclovir: monitor renal function at initiation and 1-2 times weekly 5

Special Populations

Pregnancy

• Acyclovir is the first choice for HSV infections in pregnancy due to extensive safety data 5
• Episodic therapy for first-episode and recurrent HSV can be offered during pregnancy 5
• Use in late pregnancy suppresses genital herpes outbreaks and reduces need for Cesarean delivery 5

HIV-Infected Patients

• Daily suppressive therapy (valacyclovir 500 mg twice daily, or acyclovir/famciclovir twice-daily regimens) decreases HIV concentration in plasma and genital secretions 5
• Higher doses often needed for treatment and suppression 5, 4

Common Pitfalls to Avoid

• Do not use topical acyclovir for shingles—it is substantially less effective than systemic therapy 6
• Do not stop treatment at exactly 7 days for shingles if lesions have not completely scabbed 6
• Do not use genital herpes dosing (400 mg TDS) for shingles—this is inadequate for VZV infection 6
• Do not delay treatment beyond 72 hours of rash onset for optimal efficacy in herpes zoster 6
• Do not use high-dose valacyclovir (8 g/day) in immunocompromised patients due to risk of TTP/HUS 5, 4