What is the recommended management of herpes zoster, including timing and dosing of oral antivirals (valacyclovir, famciclovir, acyclovir), pain control options, use of oral corticosteroids for severe pain, intravenous acyclovir for immunocompromised patients, and vaccination recommendations?

Management of Herpes Zoster

First-Line Antiviral Therapy for Uncomplicated Herpes Zoster

For immunocompetent adults with uncomplicated herpes zoster, initiate oral valacyclovir 1000 mg three times daily for 7 days, starting within 72 hours of rash onset. 1, 2

The three FDA-approved oral antivirals are equally effective for uncomplicated disease:

• Valacyclovir 1000 mg three times daily for 7 days (preferred due to convenient dosing and superior pain reduction compared to acyclovir) 1, 2, 3
• Famciclovir 500 mg three times daily for 7 days (equivalent efficacy to valacyclovir with convenient dosing) 1, 2, 4
• Acyclovir 800 mg five times daily for 7-10 days (effective but requires more frequent dosing, potentially reducing adherence) 1, 2, 5

Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period. 1 This is the key clinical endpoint that correlates with reduced viral shedding and transmission risk.

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, 2 However, observational data suggest that starting valacyclovir beyond 72 hours may still provide benefit for pain reduction, so treatment should not be withheld if patients present late. 3

Intravenous Acyclovir for Complicated or Disseminated Disease

Switch to intravenous acyclovir 10 mg/kg every 8 hours for complicated herpes zoster, continuing for a minimum of 7-10 days until all lesions have scabbed. 6, 1, 2

Indications for IV Acyclovir:

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1
• Severe immunosuppression (active chemotherapy, HIV with low CD4 count, organ transplant recipients) 6, 1, 7
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
• Complicated ophthalmic or facial disease with suspected CNS involvement 1
• Inability to take or absorb oral medications 7

For immunocompromised patients with uncomplicated herpes zoster, oral antivirals (valacyclovir, famciclovir, or acyclovir) are appropriate with close outpatient monitoring, but maintain a low threshold for escalating to IV therapy if lesions fail to improve within 7-10 days. 6, 1, 7

Renal Dose Adjustments

Assess baseline renal function before initiating any antiviral and monitor weekly during IV therapy. 1 All three oral antivirals and IV acyclovir require dose reduction based on creatinine clearance to prevent drug accumulation and neurotoxicity. 1

Management of Immunosuppressive Medications

In patients with disseminated or invasive herpes zoster, temporarily reduce or discontinue immunosuppressive medications when clinically feasible. 6, 1 Restart immunosuppression only after all vesicular lesions have crusted, fever has resolved, and the patient has shown clinical improvement on antiviral therapy. 6, 1

Pain Management

Acute Neuropathic Pain

Initiate gabapentin as first-line therapy for acute zoster-associated neuropathic pain, titrating up to 2400 mg daily in divided doses. 1 Gabapentin improves sleep quality but causes somnolence in approximately 80% of patients, so counsel accordingly. 1

• Pregabalin may be added for refractory pain 1
• Over-the-counter analgesics (acetaminophen, ibuprofen) provide relief for acute pain 1
• Topical ice or cold packs reduce pain and swelling during the acute phase 1

Topical Therapies

A single application of 8% capsaicin patch (or 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic peripheral neuropathic pain. 1 To mitigate burning, apply 4% lidocaine for 60 minutes before capsaicin administration. 1

Topical anesthetics provide minimal benefit during the acute phase and are not recommended as primary therapy. 1

Role of Oral Corticosteroids

Oral corticosteroids are NOT routinely recommended for herpes zoster. 1 While prednisone may be considered as adjunctive therapy in select cases of severe, widespread disease in immunocompetent patients, the risks—particularly in elderly patients—generally outweigh benefits. 1

Absolute Contraindications to Corticosteroids:

• Immunocompromised patients (increased risk of disseminated infection) 1
• Active herpes zoster with vesicular lesions (can worsen infection and increase dissemination risk) 1
• Poorly controlled diabetes, severe osteoporosis, or history of steroid-induced psychosis 1

Never apply topical corticosteroids to active shingles lesions—this increases the risk of severe disease and dissemination. 1

Treatment Failure and Acyclovir Resistance

If lesions have not begun to resolve within 7-10 days of appropriate antiviral therapy, suspect acyclovir resistance and obtain viral culture with susceptibility testing. 1

Acyclovir resistance is rare in immunocompetent patients (<0.5%) but occurs in up to 7% of immunocompromised patients. 1 All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. 1

For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 6, 1, 7

Vaccination Recommendations

The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes. 1 This provides >90% efficacy in preventing future episodes. 1

• Administer the two-dose series after recovery from the current episode 1
• Ideally vaccinate before initiating immunosuppressive therapies (e.g., JAK inhibitors, B-cell depleting agents) 1
• For patients already on B-cell depleting therapy, give Shingrix at least 4 weeks before the next scheduled dose to maximize immunogenicity 1

The live-attenuated vaccine (Zostavax) is contraindicated in immunocompromised patients due to risk of uncontrolled viral replication. 1

Post-Exposure Prophylaxis

For varicella-susceptible individuals exposed to active herpes zoster, administer varicella-zoster immune globulin (VZIG) within 96 hours of exposure. 6, 1 High-risk populations include:

• Pregnant women 6, 1
• Immunocompromised patients 6, 1
• Premature newborns <28 weeks gestation or <1000 g 1

If VZIG is unavailable or >96 hours have passed, give oral acyclovir for 7 days beginning 7-10 days after exposure. 1

Infection Control Measures

Patients with herpes zoster remain contagious until all lesions have crusted. 1 During this period:

• Avoid contact with susceptible individuals (those without chickenpox history or vaccination) 1
• Cover lesions with clothing or dressings 1
• Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust 1
• For disseminated zoster or immunocompromised patients, implement both airborne and contact precautions in healthcare settings 1

Common Pitfalls to Avoid

• Do not discontinue antiviral therapy at exactly 7 days if lesions have not fully scabbed—continue until complete crusting 1
• Do not rely on topical antivirals—they are substantially less effective than systemic therapy 6, 1
• Do not delay IV acyclovir in immunocompromised patients with extensive disease or signs of dissemination 1, 7
• Do not use short-course antiviral regimens (1-3 days) designed for genital herpes—these are inadequate for VZV infection 1
• Do not apply topical corticosteroids to active lesions—this increases dissemination risk 1

Special Populations

Immunocompromised Patients on Specific Therapies

• Proteasome inhibitor therapy (e.g., bortezomib): Consider daily acyclovir 400 mg prophylaxis 1
• B-cell depleting therapies (e.g., rituximab, ocrelizumab): Highest risk for severe herpes zoster; consider IV acyclovir even for apparently uncomplicated disease 1
• Purine analog-based or alemtuzumab therapy: Antibiotic prophylaxis for herpes zoster is recommended 1

Pregnant Women

Intravenous acyclovir should be considered for serious viral-mediated complications (e.g., pneumonia) in pregnant women, though routine oral acyclovir is not recommended. 6 VZIG is recommended for VZV-susceptible pregnant women within 96 hours after exposure. 6, 1