What is the recommended treatment for herpes zoster in adults, including first‑line oral antivirals, dosing adjustments for renal impairment, intravenous therapy for severe disease, pain management, and steroid use?

Herpes Zoster Treatment

First-Line Oral Antiviral Therapy

For uncomplicated herpes zoster in adults, initiate oral valacyclovir 1 gram three times daily for 7–10 days, continuing until all lesions have completely scabbed. 1, 2

• Valacyclovir 1 gram three times daily is the preferred first-line agent due to superior bioavailability and convenient dosing compared to acyclovir. 1, 3

• Alternative oral options include:

  • Acyclovir 800 mg five times daily for 7–10 days (requires more frequent dosing but remains effective) 1, 2
  • Famciclovir 500 mg three times daily for 7–10 days (comparable efficacy to valacyclovir with less frequent dosing than acyclovir) 1, 4, 5

• Critical timing: 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, 6 However, observational data suggest valacyclovir may still provide benefit when started beyond 72 hours, so do not withhold treatment in late presenters. 3

• Treatment endpoint: Continue antiviral therapy until all lesions have completely scabbed—this is the key clinical endpoint, not an arbitrary 7-day duration. 1, 2 Immunocompromised patients may require extended treatment beyond 7–10 days as their lesions develop over longer periods (7–14 days) and heal more slowly. 1

Common Pitfall

Do not discontinue antivirals at exactly 7 days if lesions are still forming or have not completely scabbed; short-course regimens designed for genital herpes are inadequate for VZV infection. 1

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Renal Dose Adjustments

All oral antivirals require dose adjustment in renal impairment to prevent acute renal failure. 1

• Valacyclovir and acyclovir: Reduce frequency based on creatinine clearance (CrCl). 1

• Famciclovir dosing by CrCl: 1

  • CrCl ≥60 mL/min: 500 mg every 8 hours
  • CrCl 40–59 mL/min: 500 mg every 12 hours
  • CrCl 20–39 mL/min: 500 mg every 24 hours
  • CrCl <20 mL/min: 250 mg every 24 hours

• Monitoring: Assess baseline renal function before initiating therapy and monitor at least once or twice weekly during IV acyclovir treatment. 1

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Intravenous Acyclovir for Severe or Complicated Disease

Switch to intravenous acyclovir 10 mg/kg every 8 hours for disseminated, multi-dermatomal, ophthalmic, visceral, or CNS herpes zoster, continuing for a minimum of 7–10 days and until clinical resolution is attained. 1, 2

Indications for IV therapy:

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1
• Severe immunosuppression (active chemotherapy, HIV with low CD4 count, organ transplant recipients) 1, 2
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
• Complicated ocular or facial disease 1, 2
• Failure of oral therapy to produce lesion improvement within 7–10 days 1

Management in immunocompromised patients:

• Temporarily reduce or discontinue immunosuppressive medications when clinically feasible in cases of disseminated or invasive herpes zoster. 1, 2
• Re-introduce immunosuppression only after all vesicular lesions have crusted, fever has resolved, and the patient has shown clinical improvement on antiviral therapy. 1
• High-dose IV acyclovir remains the treatment of choice for VZV infections in severely compromised hosts. 1

Monitoring during IV therapy:

• Monitor renal function closely with dose adjustments as needed for renal impairment. 1
• Assess for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy. 1
• Ensure adequate hydration to reduce the risk of crystalluria and acyclovir-induced nephropathy. 1

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Pain Management

Initiate antiviral therapy as the primary intervention to reduce acute pain and prevent postherpetic neuralgia; adjunctive analgesics should be added based on pain severity. 7, 6

Acute pain management:

• Over-the-counter analgesics (acetaminophen, ibuprofen) for mild to moderate pain 1
• Opioid analgesics for severe acute pain 6
• Topical ice or cold packs to reduce pain and swelling during the acute phase 1

Postherpetic neuralgia prevention and treatment:

• Valacyclovir and famciclovir reduce the duration of postherpetic neuralgia significantly faster than acyclovir. 3, 4
• Famciclovir recipients experience approximately twofold faster resolution of postherpetic neuralgia compared to placebo, with median duration reduced by approximately 2 months. 4
• For established postherpetic neuralgia: tricyclic antidepressants, gabapentin, or topical lidocaine patches may be required. 7, 6

Common Pitfall

Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain management. 1

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Corticosteroid Use

Corticosteroids may be used as adjunctive therapy to antivirals in select cases of severe, widespread shingles, but carry significant risks and should generally be avoided in immunocompromised patients. 1

When to consider corticosteroids:

• Severe, widespread shingles flares in otherwise healthy adults 1
• Prednisone may provide modest benefits in reducing acute pain when combined with antivirals 6

Contraindications and high-risk populations:

• Immunocompromised patients (HIV, cancer, chronic systemic immunosuppression) should not receive corticosteroids during active shingles due to increased risk of disseminated infection. 1
• Avoid in patients with: poorly controlled diabetes, history of steroid-induced psychosis, severe osteoporosis, or prior severe steroid toxicity 1
• Elderly patients are at particular risk for corticosteroid-related complications. 1

Risks of corticosteroid use:

• Increased susceptibility to infections, hypertension, myopathy, glaucoma, aseptic necrosis, cataracts, Cushing syndrome, weight gain, and osteopenia 1
• Never apply topical corticosteroids to active shingles lesions, as this can increase the risk of severe disease and dissemination. 1

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Acyclovir-Resistant Herpes Zoster

For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 1, 2

Resistance patterns:

• Acyclovir resistance is extremely rare in immunocompetent patients (<0.5%) but occurs more frequently in immunocompromised patients (up to 7%) receiving prolonged suppressive therapy. 1
• All acyclovir-resistant strains are also resistant to valacyclovir and ganciclovir, and most are resistant to famciclovir. 1

When to suspect resistance:

• Lesions fail to begin resolving within 7–10 days of appropriate antiviral therapy 1
• Obtain viral culture with susceptibility testing if resistance is suspected 1

Foscarnet monitoring:

• Requires close monitoring of renal function and electrolytes (hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia) 2

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Infection Control and Prevention

Patients with herpes zoster should avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to individuals who have not had chickenpox or vaccination. 1

• Cover lesions with clothing or dressings to minimize transmission risk. 1
• Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust. 1
• For disseminated zoster (lesions in >3 dermatomes), implement both airborne and contact precautions. 1

Post-exposure prophylaxis:

• Varicella-zoster immune globulin (VZIG) should be administered within 96 hours of exposure to high-risk individuals (pregnant women, immunocompromised patients, premature newborns <28 weeks gestation or <1,000 g). 8, 1
• If VZIG is unavailable or >96 hours have passed, initiate a 7-day course of oral acyclovir beginning 7–10 days after exposure. 1, 2

Vaccination:

• The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes, providing >90% efficacy in preventing future recurrences. 1, 2
• Vaccination should ideally occur before initiating immunosuppressive therapies but can also be given after recovery from an acute episode. 1
• For patients on B-cell depleting therapies (e.g., ocrelizumab, rituximab), administer Shingrix at least 4 weeks prior to the next scheduled dose to maximize immunogenicity. 1