What is the recommended treatment for herpes zoster, including antiviral therapy, dosing adjustments for renal impairment, management of immunocompromised patients, ophthalmic involvement, and analgesic strategies?

Treatment of Herpes Zoster

For uncomplicated herpes zoster in immunocompetent adults, initiate oral valacyclovir 1 gram three times daily for 7 days, starting within 72 hours of rash onset, and continue treatment until all lesions have completely scabbed. 1, 2

First-Line Antiviral Therapy

Standard Oral Regimens for Immunocompetent Patients

• Valacyclovir 1000 mg orally three times daily for 7 days is the preferred first-line treatment due to superior bioavailability and convenient dosing 1, 2, 3
• Famciclovir 500 mg orally every 8 hours for 7 days is equally effective with less frequent dosing than acyclovir 1, 4, 5
• Acyclovir 800 mg orally five times daily for 7-10 days remains effective but requires more frequent administration 1, 2, 6

Critical Timing Window

• 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, 7
• Treatment initiated within 48 hours provides the fastest resolution of zoster-associated pain 5
• Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint 1, 2

Dose Adjustments for Renal Impairment

Famciclovir Renal Dosing

• CrCl ≥60 mL/min: 500 mg every 8 hours 1, 4
• CrCl 40-59 mL/min: 500 mg every 12 hours 4
• CrCl 20-39 mL/min: 500 mg every 24 hours 1, 4
• CrCl <20 mL/min: 250 mg every 24 hours 1, 4

Monitoring During IV Acyclovir

• Assess baseline renal function at treatment initiation 1
• Monitor renal function once or twice weekly during IV therapy 8, 1
• Adjust dosing as necessary for renal impairment 8, 1
• Watch for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 8, 1

Management of Immunocompromised Patients

Uncomplicated Herpes Zoster

• Oral valacyclovir or acyclovir can be used for uncomplicated disease in kidney transplant recipients and other immunocompromised patients 1, 6
• Monitor closely for signs of dissemination and visceral complications 1, 2
• Consider longer treatment duration if healing is delayed 2

Disseminated or Invasive Disease

• Intravenous acyclovir 10 mg/kg every 8 hours is mandatory for disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) 1, 2
• Continue IV therapy for minimum 7-10 days and until clinical resolution (all lesions scabbed) 1, 2
• Temporarily reduce or discontinue immunosuppressive medications when clinically feasible 1, 2
• Switch to oral therapy once clinical improvement occurs 2

High-Risk Populations

• B-cell depleting therapies (ocrelizumab, rituximab, ofatumumab) carry the highest risk of severe herpes zoster and may require IV therapy even for apparently uncomplicated presentations 1
• Active chemotherapy patients should receive IV acyclovir 10 mg/kg every 8 hours due to high dissemination risk 1
• HIV-infected patients may require higher oral doses (acyclovir 400 mg 3-5 times daily) until clinical resolution 1

Ophthalmic Involvement (Herpes Zoster Ophthalmicus)

Treatment Approach

• Oral valacyclovir 1 gram three times daily or famciclovir at VZV-appropriate doses (500 mg three times daily) with particular urgency given risk of vision-threatening complications 1
• Valacyclovir and acyclovir demonstrate similar efficacy for controlling ocular complications 3
• Escalate to IV acyclovir for complicated ocular disease with suspected CNS involvement 1

Ramsay Hunt Syndrome (Herpes Zoster Oticus)

• Valacyclovir 1 gram orally three times daily for 7 days combined with systemic corticosteroids 9
• Initiate treatment as soon as possible, ideally within 72 hours of symptom onset 9
• Do not rely on topical antivirals—systemic therapy is mandatory 9
• Do not delay treatment waiting for laboratory confirmation; diagnosis is clinical 9

Analgesic Strategies

Acute Pain Management

• Over-the-counter analgesics (acetaminophen, ibuprofen) for acute pain relief 1
• Topical ice or cold packs to reduce pain and swelling during acute phase 1
• Topical anesthetics provide minimal benefit and are not recommended as primary therapy 1

Postherpetic Neuralgia Prevention and Treatment

• Valacyclovir and famciclovir reduce the incidence and severity of postherpetic neuralgia more effectively than acyclovir 3, 7, 5
• Tricyclic antidepressants, antiseizure drugs, opioids, and topical analgesics offer pain relief for established postherpetic neuralgia and may be combined 7
• Oral antivirals do not reliably prevent postherpetic neuralgia, which remains common in older patients 7

Adjunctive Corticosteroids

• Prednisone may be used as adjunctive therapy in select cases of severe, widespread shingles 1
• Avoid in immunocompromised patients due to increased risk of disseminated infection 1
• Contraindicated in patients with poorly controlled diabetes, history of steroid-induced psychosis, severe osteoporosis, or prior severe steroid toxicity 1

Treatment Failure and Acyclovir Resistance

Recognizing Treatment Failure

• Suspect resistance if lesions do not begin to resolve within 7-10 days after initiation of therapy 8, 1
• Obtain viral culture with susceptibility testing to confirm drug resistance 8, 1
• Acyclovir resistance is rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients 1

Management of Confirmed Resistance

• Foscarnet 40 mg/kg IV every 8 hours until clinical resolution is the treatment of choice for acyclovir-resistant VZV 8, 1, 2
• 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 1
• Monitor renal function and electrolytes closely (hypocalcemia, hypophosphatemia, hypomagnesemia, hypokalemia) during foscarnet therapy 2

Infection Control and Prevention

Isolation Precautions

• Patients should avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to those without prior chickenpox or vaccination 1, 2
• 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

• Varicella-zoster immune globulin (VZIG) within 96 hours of exposure for VZV-susceptible high-risk individuals (pregnant women, immunocompromised patients, premature newborns) 1, 2
• If VZIG unavailable or >96 hours have passed, give 7-day course of oral acyclovir beginning 7-10 days after exposure 1, 2

Vaccination

• Recombinant zoster vaccine (Shingrix) for all adults aged ≥50 years, regardless of prior herpes zoster episodes, providing >90% efficacy 1, 2
• Administer at least 4 weeks prior to initiating B-cell depleting therapy to maximize immunogenicity 1
• Vaccination can be given after recovery from acute episode to prevent future recurrences 1, 2

Common Pitfalls to Avoid

• Do not use topical antivirals—they are substantially less effective than systemic therapy 1, 2
• Do not stop treatment at exactly 7 days if lesions are still forming or have not completely scabbed 1, 2
• Do not use short-course therapy (1-3 days) designed for genital herpes—it is inadequate for VZV infection 8, 1
• Do not underdose in immunocompromised patients—they may require IV therapy or higher oral doses 1
• Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephrotoxicity 1