What is the recommended treatment for shingles (herpes zoster)?

Treatment of Shingles (Herpes Zoster)

For uncomplicated shingles in immunocompetent adults, start oral valacyclovir 1000 mg three times daily for 7 days, initiated within 72 hours of rash onset, and continue treatment until all lesions have completely scabbed. 1, 2

First-Line Antiviral Therapy for Uncomplicated Disease

Valacyclovir is the preferred first-line agent due to superior bioavailability, less frequent dosing (improving adherence), and faster resolution of zoster-associated pain compared to acyclovir. 1, 3

Standard Dosing Regimens:

• Valacyclovir: 1000 mg orally three times daily for 7 days 1, 2
• Famciclovir: 500 mg orally three times daily (every 8 hours) for 7 days 1, 4
• Acyclovir: 800 mg orally five times daily for 7-10 days (less preferred due to frequent dosing) 1, 2

Critical Timing:

• Initiate treatment within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1, 5
• Treatment started after 72 hours may still provide benefit, particularly for pain reduction, but efficacy is reduced. 3

Treatment Endpoint:

• Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint. 1, 2
• If lesions continue to form or have not scabbed by day 7, extend treatment duration. 1

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Escalation to Intravenous Therapy

Switch to intravenous acyclovir 10 mg/kg every 8 hours for the following high-risk scenarios: 1, 2

Indications for IV Therapy:

• 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 facial/ophthalmic zoster with suspected CNS involvement or severe ocular disease 1
• Visceral organ involvement (hepatitis, pneumonia) 1

IV Treatment Duration:

• Continue IV acyclovir for minimum 7-10 days and until clinical resolution (all lesions scabbed, fever resolved). 1, 2
• Switch to oral therapy once clinical improvement occurs to complete the treatment course. 2

Immunosuppression Management:

• Temporarily reduce or discontinue immunosuppressive medications in cases of disseminated or invasive herpes zoster when clinically feasible. 1, 2
• Restart immunosuppression only after all vesicular lesions have crusted, fever has resolved, and the patient shows clinical improvement on antiviral therapy. 1

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Special Populations

Immunocompromised Patients (Uncomplicated Disease):

• Oral valacyclovir or famciclovir can be used for uncomplicated dermatomal disease, but consider longer treatment duration if healing is delayed. 1, 2
• Monitor closely for dissemination and visceral complications. 2
• All immunocompromised patients require antiviral treatment regardless of timing beyond 72 hours. 2

HIV-Infected Patients:

• Famciclovir 500 mg twice daily for 7 days for recurrent orolabial or genital herpes. 4
• Higher oral doses may be needed for herpes zoster (up to 800 mg acyclovir 5-6 times daily). 1
• Consider long-term acyclovir prophylaxis (400 mg 2-3 times daily) for frequent recurrences. 1

Renal Impairment:

• Mandatory dose adjustments to prevent acute renal failure. 1, 4
• For famciclovir in herpes zoster: 4
  • 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
  • Hemodialysis: 250 mg following each dialysis

Facial/Ophthalmic Involvement:

• Urgent ophthalmology referral required for trigeminal V1 distribution (ophthalmic herpes zoster) to assess for ocular complications. 6
• Initiate oral valacyclovir 1000 mg three times daily with particular urgency given risk of vision-threatening complications. 1

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Acyclovir-Resistant Cases

Suspect resistance if lesions fail to begin resolving within 7-10 days of appropriate antiviral therapy. 1

Management:

• Obtain viral culture with susceptibility testing. 1
• Switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution for confirmed acyclovir-resistant VZV. 1, 2
• All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. 1
• Resistance is rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients. 1

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Monitoring and Safety

Renal Function Monitoring:

• Baseline renal function required before initiating IV acyclovir. 1
• Monitor renal function once or twice weekly during IV therapy, with dose adjustments for any impairment. 1
• Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephrotoxicity. 1

Treatment Failure Assessment:

• If lesions have not begun to resolve by 7-10 days, suspect acyclovir resistance and obtain viral culture with susceptibility testing. 1

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Infection Control

• 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

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Prevention: Vaccination

The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes. 1, 2

• Provides >90% efficacy in preventing future herpes zoster episodes. 1
• Can be administered after recovery from acute shingles to prevent recurrence. 1
• Should be given before initiating immunosuppressive therapies when possible. 1
• For patients on B-cell depleting therapy (e.g., rituximab, ocrelizumab), administer at least 4 weeks prior to the next scheduled dose to maximize immunogenicity. 1

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Common Pitfalls to Avoid

• Do not use topical antivirals—they are substantially less effective than systemic therapy and are not recommended. 1, 2
• Do not discontinue treatment at exactly 7 days if lesions are still forming or have not completely scabbed. 1
• Do not use corticosteroids in immunocompromised patients during active shingles due to increased risk of disseminated infection. 1
• Do not delay treatment waiting for laboratory confirmation in typical presentations—clinical diagnosis is sufficient to initiate therapy. 1
• Do not underdose acyclovir—400 mg three times daily is only appropriate for genital herpes or HSV suppression, not for shingles (requires 800 mg five times daily). 1