What is the recommended oral antiviral regimen for an adult with herpes zoster, including drug choices, dosing, duration, timing of initiation, and adjustments for renal impairment or special populations?

Oral Antiviral Treatment for Herpes Zoster (Shingles)

For immunocompetent adults with herpes zoster, initiate oral valacyclovir 1000 mg three times daily for 7 days within 72 hours of rash onset, continuing until all lesions have completely scabbed. 1

First-Line Oral Antiviral Options

Valacyclovir is the preferred first-line agent due to superior bioavailability, convenient three-times-daily dosing, and proven superiority over acyclovir in reducing duration of zoster-associated pain and postherpetic neuralgia. 2, 3

• Valacyclovir 1000 mg orally three times daily for 7 days 1, 2
• Famciclovir 500 mg orally every 8 hours for 7 days 4, 5
• Acyclovir 800 mg orally five times daily for 7-10 days (requires more frequent dosing, less convenient) 1, 6

All three agents demonstrate similar efficacy for acute lesion healing, but valacyclovir and famciclovir offer better bioavailability and less frequent dosing compared to acyclovir. 7, 2

Critical Timing of Initiation

Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1, 2 Treatment started within 48 hours provides maximum benefit for hastening rash healing. 6

However, do not withhold treatment if presenting beyond 72 hours—observational data suggest valacyclovir may still reduce duration of zoster-associated pain when initiated later than 72 hours, particularly in patients with ongoing new lesion formation or severe pain. 2

Treatment Duration and Endpoint

Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period. 1 This is the key clinical endpoint. If lesions remain active beyond 7 days, extend treatment duration accordingly. 1

Immunocompromised patients may develop new lesions for 7-14 days and heal more slowly, requiring treatment extension well beyond the standard 7-10 day course. 1

Renal Dose Adjustments

Mandatory dose adjustments are required for patients with renal impairment to prevent acute renal failure. 1

Famciclovir Dosing by Creatinine Clearance (for Herpes Zoster):

• CrCl ≥60 mL/min: 500 mg every 8 hours 4
• CrCl 40-59 mL/min: 500 mg every 12 hours 4
• CrCl 20-39 mL/min: 500 mg every 24 hours 4
• CrCl <20 mL/min: 250 mg every 24 hours 4
• Hemodialysis: 250 mg following each dialysis 4

Similar proportional reductions apply to valacyclovir and acyclovir based on creatinine clearance. 1

Special Populations Requiring Intravenous Therapy

Switch to intravenous acyclovir 10 mg/kg every 8 hours for the following high-risk scenarios: 1

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, hemorrhagic lesions)
• Severely immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant recipients)
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome)
• Complicated ocular disease or facial zoster with suspected CNS involvement
• Failure to respond to oral therapy within 7-10 days

Continue IV acyclovir for minimum 7-10 days and until all lesions have completely scabbed. 1 Consider temporary reduction or discontinuation of immunosuppressive medications if clinically feasible. 1

Monitoring During Treatment

• Baseline renal function at initiation, then monitor once or twice weekly during IV acyclovir therapy 1
• Assess for treatment failure if lesions fail to begin resolving within 7-10 days—suspect acyclovir resistance and obtain viral culture with susceptibility testing 8, 1
• Monitor for dissemination in immunocompromised patients: respiratory symptoms (pneumonia), elevated transaminases (hepatitis), neurological changes (CNS involvement) 1

Management of Acyclovir-Resistant Herpes Zoster

For confirmed acyclovir-resistant VZV (rare in immunocompetent, up to 7% in immunocompromised): 8, 1

• Foscarnet 40 mg/kg IV every 8 hours until clinical resolution is the treatment of choice 8, 1
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be considered for external lesions 1

Important Clinical Pitfalls to Avoid

• Never use topical antivirals for herpes zoster—they are substantially less effective than systemic therapy and are not recommended 1
• Do not discontinue treatment at exactly 7 days if lesions are still forming or have not completely scabbed 1
• Do not apply topical corticosteroids to active shingles lesions—this can worsen infection, increase dissemination risk, and is contraindicated in immunocompromised patients 1
• Do not delay IV therapy in severely immunocompromised patients with facial involvement or multi-dermatomal disease 1

Infection Control Measures

Patients remain contagious until all lesions have crusted. 1 They should:

• Avoid contact with varicella-susceptible individuals (pregnant women, immunocompromised patients, premature newborns) 1
• Cover lesions with clothing or dressings to minimize transmission risk 1
• Maintain physical separation of at least 6 feet from other patients in healthcare settings 1

For disseminated zoster or immunocompromised patients, implement both airborne and contact precautions. 1

Post-Recovery Vaccination

The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults ≥50 years after recovery from acute herpes zoster, regardless of prior episodes, providing >90% efficacy in preventing future recurrences. 1 Administer the two-dose series after complete resolution of the current episode.