What is the recommended management of herpes zoster in adults, including antiviral regimen, pain control, and special considerations for immunocompromised, pregnant, and patients over 50?

Treatment of Herpes Zoster (Shingles)

For uncomplicated herpes zoster in immunocompetent adults, initiate oral valacyclovir 1 gram three times daily or famciclovir 500 mg three times daily within 72 hours of rash onset, continuing treatment until all lesions have completely scabbed. 1

Antiviral Therapy: First-Line Treatment

Standard Oral Regimens for Immunocompetent Patients

• Valacyclovir 1 gram orally three times daily for 7-10 days is the preferred first-line agent due to superior bioavailability and less frequent dosing compared to acyclovir, which improves adherence. 1, 2
• Famciclovir 500 mg orally three times daily for 7-10 days offers equivalent efficacy with better bioavailability than acyclovir. 1
• Acyclovir 800 mg orally five times daily for 7-10 days remains effective but requires more frequent dosing. 1, 3
• Treatment must begin within 72 hours of rash onset to reduce acute pain severity, accelerate lesion healing, and prevent postherpetic neuralgia; treatment initiated within 48 hours provides optimal efficacy. 1
• Continue antiviral therapy until all lesions have completely scabbed, not for an arbitrary 7-day period—this is the key clinical endpoint. 1

Critical Timing Considerations

The 72-hour window represents the maximum timeframe for optimal antiviral efficacy, though treatment may still provide benefit if started later, particularly in immunocompromised patients or those with ophthalmic involvement. 1

Intravenous Therapy: When to Escalate

Indications for IV Acyclovir

Switch to intravenous acyclovir 10 mg/kg every 8 hours for: 1

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

IV Treatment Duration and Monitoring

• Continue IV acyclovir for minimum 7-10 days and until clinical resolution (all lesions completely scabbed). 1
• Monitor renal function at initiation and once or twice weekly during IV therapy; adjust dosing for any renal impairment to prevent nephrotoxicity. 1
• Ensure adequate hydration during IV acyclovir to reduce risk of crystalluria and acyclovir-induced nephropathy. 1
• Watch for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy. 1

Special Population Management

Immunocompromised Patients

• Immunocompromised patients with uncomplicated herpes zoster should receive oral acyclovir or valacyclovir, but may require higher doses or extended duration. 1
• For disseminated or invasive disease, use IV acyclovir 10 mg/kg every 8 hours with temporary reduction in immunosuppressive medication when clinically feasible. 1
• Do not resume immunosuppressive agents until all vesicular lesions have crusted, fever has resolved, and clinical improvement is evident on antiviral therapy. 1
• Immunocompromised patients may develop new lesions for 7-14 days and heal more slowly, requiring treatment extension well beyond 7-10 days. 1

Pregnant Women

• Indications for antiviral prophylaxis are the same as for non-pregnant women. 4
• Choice of antiviral agents should be individualized after consultation with a specialist, though acyclovir is pregnancy category B with no pattern of adverse pregnancy outcomes reported. 3
• Administer varicella-zoster immune globulin (VZIG) within 96 hours of exposure for VZV-susceptible pregnant women. 1

Patients Over 50 Years

• The median duration of pain after healing (postherpetic neuralgia) was 40-59 days in subjects aged >50 years treated with valacyclovir or acyclovir. 2
• Elderly patients are more likely to have reduced renal function requiring dose reduction, and experience more frequent nausea, vomiting, dizziness, somnolence, hallucinations, confusion, and coma. 3
• The recombinant zoster vaccine (Shingrix) is recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes, to prevent future recurrences. 1

Renal Impairment

• Mandatory dose adjustments based on creatinine clearance to prevent acute renal failure: 1
  • Famciclovir: 500 mg every 8 hours for CrCl ≥60 mL/min; reduce to 250 mg every 24 hours for CrCl <20 mL/min
  • Valacyclovir and acyclovir require similar adjustments per FDA labeling

Pain Management

Acute Zoster Pain

• Gabapentin is the first-line oral agent for acute neuropathic pain, titrated in divided doses up to 2400 mg per day. 1
• Gabapentin improves sleep quality but causes somnolence in approximately 80% of patients—counsel accordingly. 1
• Over-the-counter analgesics (acetaminophen, ibuprofen) relieve acute pain in otherwise healthy adults. 1
• Topical ice or cold packs reduce pain and swelling during the acute phase. 1
• Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain. 1

Postherpetic Neuralgia Prevention and Treatment

• Early initiation of antivirals within 72 hours is proven to reduce risk of postherpetic neuralgia. 5, 6
• For patients at high risk of postherpetic neuralgia, consider early initiation of gabapentin or pregabalin. 7
• For established postherpetic neuralgia: 1
  • Gabapentin or pregabalin as first-line systemic agents
  • Tricyclic antidepressants (if not already on one)
  • Single application of 8% capsaicin patch provides analgesia lasting ≥12 weeks
  • Apply 4% lidocaine for 60 minutes before capsaicin to mitigate burning

Treatment Failure and Resistance

Recognizing Treatment Failure

• Suspect acyclovir resistance when cutaneous lesions have not begun to resolve within 7-10 days after starting therapy. 1
• Obtain viral culture with susceptibility testing to confirm resistance. 1
• Acyclovir resistance is extremely rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients. 1

Management of Acyclovir-Resistant VZV

• For confirmed acyclovir-resistant herpes zoster, use 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
• Topical cidofovir gel 1% applied once daily for 5 consecutive days may be an alternative option. 1

Infection Control and Prevention

Isolation Precautions

• Patients with herpes zoster should avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to those without prior chickenpox or vaccination. 1
• Cover lesions with clothing or dressings to minimize transmission risk. 1
• For disseminated zoster (>3 dermatomes), implement both airborne and contact precautions. 1
• Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust. 1

Post-Exposure Prophylaxis

• Administer VZIG within 96 hours of exposure for high-risk individuals: VZV-susceptible pregnant women, immunocompromised patients, and premature newborns <28 weeks gestation or <1,000 g. 1
• If VZIG is unavailable or >96 hours have passed, give 7-day course of oral acyclovir beginning 7-10 days after varicella exposure. 1

Vaccination Strategies

Timing After Acute Episode

• Administer recombinant zoster vaccine (Shingrix) no earlier than 2 months after complete clinical resolution of the acute episode to allow lesion healing and immune recovery. 1
• The 2-month interval is based on documented evidence showing this is the minimum interval between an episode and potential recurrence. 8
• Complete the 2-dose Shingrix series (doses 2-6 months apart) for optimal protection, ideally before initiating or resuming highly immunosuppressive therapy. 1, 8

Vaccine Selection

• Shingrix (recombinant zoster vaccine) is the only appropriate vaccine for immunocompromised patients—it is non-live and provides >90% efficacy in preventing future recurrences. 1, 8
• Live-attenuated zoster vaccine (Zostavax) is absolutely contraindicated in immunocompromised patients due to risk of uncontrolled viral replication. 4, 1, 8
• For immunocompromised adults aged ≥18 years, the second Shingrix dose can be given 1-2 months after the first if a shorter schedule is beneficial. 8

Common Pitfalls to Avoid

• Do not use topical acyclovir for shingles—it is substantially less effective than systemic therapy. 1
• Do not discontinue antiviral therapy at exactly 7 days if lesions are still forming or have not completely scabbed; short-course therapy designed for genital herpes is inadequate for VZV infection. 1
• Do not apply topical corticosteroids to active shingles lesions—this increases risk of severe disease and dissemination, particularly in immunocompromised patients. 1
• Do not use oral corticosteroids routinely—their benefits in pain reduction do not outweigh serious risks (infections, hypertension, myopathy, glaucoma, osteopenia). 1
• Do not miss vaccination opportunities—older adults who have had shingles remain at risk for recurrence and should receive Shingrix after recovery. 8