What is the recommended treatment regimen for herpes zoster in adults, including antiviral selection, dosing, duration, analgesia, and special considerations for severe disease, ocular involvement, immunocompromised status, renal impairment, and patients aged ≥50 years?

Treatment Regimen for Shingles (Herpes Zoster)

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

First-Line Antiviral Selection and Dosing

Standard Oral Regimens (Immunocompetent Adults)

Choose one of the following:

• Valacyclovir 1000 mg three times daily for 7 days (preferred for superior bioavailability and less frequent dosing) 1, 2
• Famciclovir 500 mg every 8 hours for 7 days 1, 3
• Acyclovir 800 mg five times daily for 7-10 days (alternative if others unavailable, requires more frequent dosing) 1, 4

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. However, treatment beyond 72 hours may still provide benefit and should not be withheld 1.

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

Renal Dose Adjustments

Mandatory dose adjustments for renal impairment 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 1
• Valacyclovir and acyclovir: Adjust based on creatinine clearance per standard renal dosing guidelines 1
• Monitor renal function at baseline and weekly during IV acyclovir therapy 1

Indications for Intravenous Acyclovir

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

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1
• Severely immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant recipients, high-dose corticosteroids >40 mg prednisone daily) 1
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) 1
• Complicated ocular/facial disease (herpes zoster ophthalmicus with severe involvement) 1, 5
• Failure to improve on oral therapy within 7-10 days 1

Duration: Continue IV acyclovir for a minimum of 7-10 days and until clinical resolution (all lesions completely scabbed) 1.

Immunosuppression management: Consider temporary reduction or discontinuation of immunosuppressive medications in disseminated or invasive disease if clinically feasible 1. Re-introduce only after all vesicular lesions have crusted, fever has resolved, and clinical improvement is documented 1.

Special Population Considerations

Herpes Zoster Ophthalmicus (HZO)

Immediate management: 5

• Initiate oral antiviral therapy immediately (valacyclovir 1000 mg three times daily or famciclovir 500 mg three times daily for 7 days) 5
• Arrange same-day or next-day ophthalmology consultation for comprehensive slit-lamp examination 5
• Apply non-preserved ocular lubricants (hyaluronate or carmellose drops) every 2 hours 5
• Consider topical corticosteroids (dexamethasone 0.1% twice daily) only in conjunction with systemic antivirals for stromal keratitis or uveitis 5
• Never use topical corticosteroids without concurrent systemic antivirals—steroids potentiate viral replication and can worsen disease 5

Escalate to IV acyclovir 10 mg/kg every 8 hours if: 5

• Immunocompromised status 5
• Disseminated disease 5
• Failure to improve within 7-10 days 5

Immunocompromised Patients

For uncomplicated herpes zoster in immunocompromised patients: 1

• Oral therapy: Higher doses may be needed—acyclovir 400 mg orally 3-5 times daily until clinical resolution 1
• Consider IV therapy early given high risk of dissemination 1

For disseminated or invasive disease: 1

• IV acyclovir 10 mg/kg every 8 hours is mandatory 1
• High-dose IV acyclovir remains the treatment of choice for VZV infections in severely compromised hosts 1
• Immunocompromised patients may require extended treatment well beyond 7-10 days as lesions develop over longer periods (7-14 days) and heal more slowly 1

Patients Aged ≥50 Years

Standard oral antiviral therapy as above, with particular attention to: 1

• Postherpetic neuralgia prevention: Oral antivirals significantly reduce duration and intensity of zoster-associated pain in elderly patients when initiated within 72 hours 4, 6
• Renal function monitoring: Elderly patients are at higher risk for renal impairment; adjust doses accordingly 1
• Vaccination after recovery: Strongly recommend recombinant zoster vaccine (Shingrix) ≥2 months after acute symptoms resolve to prevent recurrence 1, 7

Analgesia and Symptomatic Management

Acute Pain Management

• Over-the-counter analgesics: Acetaminophen and ibuprofen for acute pain relief 1
• Topical measures: Ice or cold packs to reduce pain and swelling during acute phase 1
• Avoid topical antivirals: Substantially less effective than systemic therapy and not recommended 1

Important: Topical anesthetics provide minimal benefit and are not recommended as primary therapy 1.

Skin Care

• Keep lesions clean and dry 1
• Avoid applying products to active vesicular lesions 1
• Emollients may be used after lesions have crusted to prevent excessive dryness 1

Management of Treatment Failure and Acyclovir Resistance

Suspect acyclovir resistance if lesions fail to begin resolving within 7-10 days despite appropriate therapy: 1

• Obtain viral culture with susceptibility testing 1
• Acyclovir-resistant VZV is rare in immunocompetent adults but occurs in up to 7% of immunocompromised patients 1

For confirmed acyclovir-resistant VZV: 1

• 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

Infection Control and Prevention

Isolation Precautions

• Patients should avoid contact with susceptible individuals (those who have not had chickenpox or vaccination) until all lesions have crusted 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 or immunocompromised patients: Implement airborne and contact precautions in addition to standard precautions 1

Post-Exposure Prophylaxis

For VZV-susceptible individuals exposed to active herpes zoster: 1

• Varicella zoster immunoglobulin (VZIG) within 96 hours of exposure for high-risk individuals (pregnant women, immunocompromised patients, premature newborns <28 weeks or <1,000 g) 1
• If VZIG unavailable or >96 hours have passed: 7-day course of oral acyclovir beginning 7-10 days after exposure 1

Vaccination for Prevention

Recombinant zoster vaccine (Shingrix) is strongly recommended: 7

• All adults aged ≥50 years, regardless of prior herpes zoster episodes 1, 7
• Immunocompromised adults aged ≥18 years 7
• Two-dose series: Second dose given 2-6 months after first dose (or 1-2 months for immunocompromised adults) 7
• After acute herpes zoster episode: Wait ≥2 months after symptoms resolve before vaccination 7
• Efficacy: 97.2% in preventing herpes zoster in adults aged ≥50 years, with protection persisting >8 years 7

Vaccination is particularly important because: 7

• Having one episode of shingles does not provide reliable protection against recurrence (10.3% cumulative recurrence risk at 10 years) 7
• Prior vaccination with Zostavax does not provide adequate long-term protection (efficacy drops to 14.1% by year 10) 7

Common Pitfalls to Avoid

• Do not discontinue antivirals 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 use topical antivirals—they are substantially less effective than systemic therapy 1
• Do not use topical corticosteroids without concurrent systemic antivirals in HZO—steroids potentiate viral replication 5
• Do not delay treatment beyond 72 hours when possible, but do not withhold treatment if presenting later 1
• Do not forget renal dose adjustments—failure to adjust can lead to acute renal failure 1
• Do not use live-attenuated Zostavax vaccine in immunocompromised patients—only Shingrix is appropriate 7
• Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephropathy 1