Treatment of Herpes Zoster
First-Line Antiviral Therapy for Immunocompetent Adults
For uncomplicated herpes zoster in immunocompetent adults, oral valacyclovir 1 gram three times daily for 7–10 days is the recommended first-line treatment, initiated within 72 hours of rash onset and continued until all lesions have completely scabbed. 1, 2
Antiviral Selection and Dosing
Valacyclovir 1 gram orally three times daily for 7–10 days is preferred due to superior bioavailability, less frequent dosing (improving adherence), and faster resolution of zoster-associated pain compared to acyclovir. 1, 2, 3, 4
Acyclovir 800 mg orally five times daily for 7–10 days is an effective alternative when valacyclovir is unavailable, though the five-times-daily regimen reduces patient compliance. 1, 2, 5
Famciclovir 500 mg orally three times daily for 7–10 days offers similar efficacy to valacyclovir with better bioavailability than acyclovir, and is particularly useful for patients with gastrointestinal intolerance to acyclovir. 1, 2, 3, 4
Critical Timing and Duration
Treatment must be initiated within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia, though some benefit may occur with later initiation. 1, 2, 3, 4
Continue antiviral therapy until all lesions have completely scabbed, not for an arbitrary 7-day period—this is the key clinical endpoint. 1, 2
Immunocompromised patients may require treatment extension well beyond 7–10 days because their lesions continue to develop over longer periods (7–14 days) and heal more slowly. 1
Pain Management for Acute Herpes Zoster
First-Line Analgesic Therapy
Gabapentin is the first-line oral agent for acute neuropathic pain due to herpes zoster, titrated in divided doses up to 2400 mg per day, though somnolence occurs in roughly 80% of treated individuals. 1
Over-the-counter analgesics such as acetaminophen and ibuprofen are recommended to relieve acute pain in otherwise healthy adults. 1
Application of topical ice or cold packs can reduce pain and swelling during the acute phase. 1
Adjunctive Pain Management
Pregabalin may be added for patients whose pain remains uncontrolled with gabapentin alone, particularly in postherpetic neuralgia. 1
A single application of an 8% capsaicin patch (or 30-minute cream application) provides analgesia lasting at least 12 weeks for chronic peripheral neuropathic pain; apply 4% lidocaine for 60 minutes before capsaicin to mitigate burning. 1
Topical anesthetics provide minimal benefit and are not recommended as primary therapy for acute zoster pain management. 1
Corticosteroid Caution
- Prednisone may be used as adjunctive therapy to antivirals in select cases of severe, widespread shingles, but carries significant risks in elderly patients and should generally be avoided in immunocompromised patients due to increased risk of disseminated infection. 1
Treatment for Severely Immunocompromised Patients
For severely immunocompromised patients (active chemotherapy, HIV with low CD4 count, organ transplant recipients, or those on B-cell depleting therapies), intravenous acyclovir 10 mg/kg every 8 hours is the treatment of choice, continuing for a minimum of 7–10 days and until all lesions have completely scabbed. 1, 2, 6
Indications for Intravenous Therapy
Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) requires IV acyclovir. 1, 2
Complicated facial zoster with suspected CNS involvement (encephalitis, meningitis, Guillain-Barré syndrome) or severe ophthalmic disease requires IV acyclovir. 1, 2
Severe immunosuppression (active chemotherapy, HIV infection, organ transplantation, B-cell depleting therapies) warrants IV therapy even for uncomplicated dermatomal disease. 1, 6
Inability to absorb oral medication or lack of clinical improvement after 7–10 days of appropriate oral therapy necessitates switching to IV acyclovir. 1
Immunosuppression Management
Temporary reduction or discontinuation of immunosuppressive medications should be considered in cases of disseminated or invasive herpes zoster when clinically feasible. 1, 2
Re-introduction of immunosuppressive agents is recommended only after all vesicular lesions have crusted, fever has resolved, and the patient has shown clinical improvement on antiviral therapy. 1
Monitoring Requirements
Baseline renal function should be assessed at treatment initiation and monitored once or twice weekly during IV acyclovir therapy, with dose adjustments for renal impairment. 1, 2
Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy. 1
Ensure adequate hydration during systemic acyclovir or valacyclovir therapy to reduce the risk of crystalluria and acyclovir-induced nephropathy. 1
Special Populations and Situations
Renal Impairment
Renal impairment (creatinine clearance <50 mL/min) mandates dose reduction for all oral antivirals to prevent drug accumulation and neurotoxicity. 1
For valacyclovir: CrCl 30–49 mL/min → 500 mg–1 g every 12 hours; CrCl 10–29 mL/min → 500 mg–1 g every 24 hours; CrCl <10 mL/min → 500 mg every 24 hours. 1
For famciclovir: CrCl ≥60 mL/min → 500 mg every 8 hours; CrCl <20 mL/min → 250 mg every 24 hours. 1, 2
Acyclovir-Resistant Herpes Zoster
Suspect acyclovir resistance when cutaneous lesions have not begun to resolve within 7–10 days after starting therapy; obtain viral culture with susceptibility testing. 1, 2
For confirmed acyclovir-resistant VZV, foscarnet 40 mg/kg IV every 8 hours until clinical resolution is the treatment of choice. 1, 2
All acyclovir-resistant strains are also resistant to valacyclovir, and most are resistant to famciclovir. 1
Acyclovir resistance is extremely rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients. 1
Pregnancy
In pregnant patients who develop serious VZV-related complications such as pneumonia, intravenous acyclovir should be initiated. 1
Varicella-zoster immune globulin (VZIG) within 96 hours of exposure is recommended for VZV-susceptible pregnant women. 1
Common Pitfalls and Caveats
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, 2
Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended for herpes zoster. 1, 2
Starting treatment later than 72 hours after rash onset may reduce effectiveness, though some benefit may still occur. 1, 2, 3
Monitor closely for dissemination and visceral complications in immunocompromised patients; if signs occur, switch to intravenous antiviral therapy immediately. 1, 5, 6
Patients with herpes zoster should avoid contact with susceptible individuals until all lesions have crusted, as lesions are contagious to individuals who have not had chickenpox or vaccination. 1
Prevention
The recombinant zoster vaccine (Shingrix) is strongly recommended for all adults aged ≥50 years, regardless of prior herpes zoster episodes, providing >90% efficacy in preventing future episodes. 1, 2
Vaccination should ideally occur before initiating immunosuppressive therapies, but can also be given after recovery from an acute episode. 1
For patients on B-cell depleting therapy, Shingrix should be given at least 4 weeks prior to the next scheduled dose to maximize immunogenicity. 1