What is the recommended treatment regimen for shingles (herpes zoster)?

Treatment Course for Shingles (Herpes Zoster)

For uncomplicated shingles in immunocompetent adults, initiate oral antiviral therapy with valacyclovir 1000 mg three times daily, famciclovir 500 mg every 8 hours, or acyclovir 800 mg five times daily for 7 days, starting within 72 hours of rash onset and continuing until all lesions have completely scabbed. 1

First-Line Oral Antiviral Options

The three FDA-approved oral antivirals are equally effective for treating herpes zoster, but differ in dosing convenience:

• Valacyclovir 1000 mg three times daily for 7 days offers superior bioavailability compared to acyclovir and requires less frequent dosing 1, 2
• Famciclovir 500 mg every 8 hours for 7 days provides comparable efficacy to valacyclovir with three-times-daily dosing 1, 3
• Acyclovir 800 mg five times daily for 7-10 days remains effective but requires more frequent administration, which may reduce adherence 1, 4

All three agents accelerate lesion healing, reduce acute pain, and shorten the duration of postherpetic neuralgia when initiated early 4, 2, 5.

Critical Timing Considerations

• 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
• Treatment is most effective when started within 48 hours, but the 72-hour window is the maximum timeframe for optimal benefit 1
• Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint 1

When to Escalate to Intravenous Therapy

Switch to intravenous acyclovir 10 mg/kg every 8 hours for:

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1
• Severely immunocompromised patients (active chemotherapy, organ transplant, HIV with low CD4 count) 1
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
• Complicated ocular or facial disease 1
• Lesions that fail to improve within 7-10 days on oral therapy 1

For immunocompromised patients, consider temporary reduction of immunosuppressive medications when clinically feasible 1.

Special Populations

Immunocompromised Patients

• Uncomplicated herpes zoster: Oral acyclovir or valacyclovir at standard doses 1
• Disseminated or invasive disease: IV acyclovir 10 mg/kg every 8 hours for minimum 7-10 days until clinical resolution 1
• Immunocompromised patients may require extended treatment beyond 7-10 days, as lesions develop over longer periods (7-14 days) and heal more slowly 1

Renal Impairment

• Mandatory dose adjustments are required to prevent acute renal failure 1, 3
• For famciclovir: 500 mg every 8 hours for CrCl ≥60 mL/min, down to 250 mg every 24 hours for CrCl <20 mL/min 1, 3
• Monitor renal function at initiation and once or twice weekly during IV acyclovir therapy 1

Management of Acyclovir-Resistant Herpes Zoster

• Resistance is extremely rare in immunocompetent patients (<0.5%) but occurs in up to 7% of immunocompromised patients 1
• If lesions fail to resolve within 7-10 days, suspect resistance and obtain viral culture with susceptibility testing 1
• For confirmed acyclovir-resistant VZV: Switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution 1
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir 1

Important Clinical Caveats

• Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended 1
• Antiviral medications do not eradicate latent virus but help control symptoms and reduce complications 1
• Patients remain contagious until all lesions have crusted; they should avoid contact with susceptible individuals (pregnant women, immunocompromised persons, those without chickenpox history) 1
• Cover lesions with clothing or dressings to minimize transmission risk 1

Adjunctive Pain Management

• Over-the-counter analgesics (acetaminophen, ibuprofen) for acute pain relief 1
• Topical ice or cold packs to reduce pain and swelling during the acute phase 1
• Prednisone may be considered as adjunctive therapy in select cases of severe, widespread shingles, but carries significant risks in elderly patients and should be avoided in immunocompromised patients 1

Prevention of Future Episodes

• The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes 1
• Vaccination provides >90% efficacy in preventing future recurrences 1
• Ideally administer before initiating immunosuppressive therapies, but can be given after recovery from acute episode 1