What is the recommended treatment for an acute episode of herpes zoster (shingles)?

Treatment of Acute Herpes Zoster (Shingles)

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

First-Line Oral Antiviral Therapy

Valacyclovir is the preferred first-line agent due to superior bioavailability and convenient dosing compared to acyclovir, requiring only three times daily administration versus five times daily. 1, 3

Standard Dosing Regimens:

• Valacyclovir: 1 gram orally three times daily for 7 days 1, 2
• Famciclovir: 500 mg orally three times daily for 7 days 4, 5
• Acyclovir: 800 mg orally five times daily for 7-10 days 6, 1

All three agents demonstrate comparable efficacy in accelerating lesion healing and reducing acute pain when initiated within 72 hours of rash onset. 7, 3, 8 Valacyclovir and famciclovir offer the additional benefit of reducing postherpetic neuralgia duration by approximately 2 months compared to placebo. 3, 5

Critical Timing Considerations:

• Treatment must begin within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating healing, and preventing postherpetic neuralgia. 1, 8
• Treatment initiated beyond 72 hours may still provide benefit, particularly for pain reduction, but efficacy is reduced. 3
• Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period—this is the key clinical endpoint. 1, 2

Indications for Intravenous Acyclovir

Switch to intravenous acyclovir 10 mg/kg every 8 hours when any of the following are present: 1, 2

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions)
• Severe immunosuppression (active chemotherapy, HIV with low CD4 count, organ transplant recipients)
• CNS complications (encephalitis, meningitis, Guillain-Barré syndrome)
• Complicated ophthalmic or facial involvement with risk of cranial nerve complications
• Inability to absorb oral medication
• Lack of clinical improvement after 7-10 days of appropriate oral therapy

For immunocompromised patients with disseminated or invasive disease, temporarily reduce or discontinue immunosuppressive medications when clinically feasible. 1, 2 Resume immunosuppression only after all vesicular lesions have crusted, fever has resolved, and the patient shows clinical improvement on antiviral therapy. 1

Special Populations

Immunocompromised Patients:

• All immunocompromised patients with herpes zoster require antiviral treatment regardless of timing. 1, 2
• Consider intravenous acyclovir even for uncomplicated disease in severely immunosuppressed hosts (e.g., patients on B-cell depleting therapies, active chemotherapy). 1
• Monitor closely for dissemination and visceral complications. 1, 2
• Treatment duration may need extension beyond 7-10 days, as lesions develop over longer periods (7-14 days) and heal more slowly. 1

Facial or Ophthalmic Involvement (Including Ramsay Hunt Syndrome):

• Initiate valacyclovir 1 gram three times daily combined with systemic corticosteroids as soon as possible, ideally within 72 hours. 9
• Facial zoster carries particular urgency due to risk of ophthalmic complications and cranial nerve involvement. 1, 9

Renal Impairment:

• Assess baseline renal function before initiating therapy. 1
• Dose adjustments are mandatory for all oral antivirals in renal impairment to prevent acute renal failure. 1
• For famciclovir: 500 mg every 8 hours if CrCl ≥60 mL/min, down to 250 mg every 24 hours if CrCl <20 mL/min. 1
• Monitor renal function weekly during intravenous acyclovir therapy. 1

Management of Treatment Failure or Resistance

Suspect acyclovir resistance if cutaneous lesions have not begun to resolve within 7-10 days after starting appropriate therapy. 1

• Obtain viral culture with susceptibility testing to confirm resistance. 1
• For confirmed acyclovir-resistant VZV, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 1, 2
• Acyclovir resistance is rare in immunocompetent patients 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

Adjunctive Pain Management

For acute neuropathic pain, initiate gabapentin as first-line therapy, titrated up to 2400 mg daily in divided doses. 1

• Pregabalin may be added for refractory pain. 1
• A single application of 8% capsaicin patch provides analgesia lasting at least 12 weeks for chronic neuropathic pain. 1
• Topical anesthetics provide minimal benefit and are not recommended as primary therapy. 1
• Over-the-counter analgesics (acetaminophen, ibuprofen) and topical ice packs can reduce acute pain and swelling. 1

Critical Pitfalls to Avoid

• Never use topical antivirals for shingles—they are substantially less effective than systemic therapy. 6, 1
• Do not discontinue treatment at exactly 7 days if lesions are still forming or have not completely scabbed. 1
• Avoid applying corticosteroid creams to active shingles lesions, as this can increase risk of severe disease and dissemination, particularly in immunocompromised patients. 1
• Do not delay treatment waiting for laboratory confirmation—diagnosis is clinical and treatment should begin immediately. 9
• Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce risk of crystalluria and nephrotoxicity. 1

Prevention and 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
• Should be administered after recovery from the current episode. 1
• Ideally given before initiating immunosuppressive therapies when possible. 1
• For patients on B-cell depleting therapy, administer at least 4 weeks prior to the next scheduled dose to maximize immunogenicity. 1

Infection Control

Patients with active herpes zoster should avoid contact with susceptible individuals until all lesions have fully crusted. 1, 2

• Cover lesions with clothing or dressings to minimize transmission risk. 1
• Implement both airborne and contact precautions for disseminated zoster (≥3 dermatomes) or in immunocompromised patients. 1
• Healthcare workers with herpes zoster should be excluded from duty until all lesions dry and crust. 1