Treatment of Shingles (Herpes Zoster)
For uncomplicated shingles in immunocompetent adults, start valacyclovir 1 gram orally three times daily for 7 days, initiated within 72 hours of rash onset and continued until all lesions have completely scabbed. 1, 2
First-Line Oral Antiviral Options
Valacyclovir is the preferred first-line agent due to superior bioavailability and convenient three-times-daily dosing compared to acyclovir's five-times-daily regimen, which improves adherence and clinical outcomes. 1, 3
Standard Dosing Regimens:
- Valacyclovir: 1 gram orally three times daily for 7 days 1, 2, 3
- 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 1, 2, 5
All three antivirals demonstrate equivalent efficacy in accelerating rash healing and reducing acute pain duration when initiated within 72 hours of rash onset. 1, 6, 7 However, valacyclovir significantly accelerates pain resolution compared to acyclovir (median 38 days versus 51 days) and reduces postherpetic neuralgia duration. 3
Critical Treatment Timing
Initiate antiviral therapy within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1, 2, 6 Treatment initiated beyond 72 hours shows reduced effectiveness, though immunocompromised patients warrant treatment regardless of timing. 1, 4
Treatment Duration and Endpoint
Continue antiviral therapy until all lesions have completely scabbed, not just for an arbitrary 7-day period. 1, 2 This is the key clinical endpoint. Treatment may require extension beyond 7-10 days if new lesions continue forming or healing remains incomplete, particularly in immunocompromised patients who develop lesions over 7-14 days and heal more slowly. 1, 2
Escalation to Intravenous Therapy
Switch to intravenous acyclovir 10 mg/kg every 8 hours for:
- Disseminated or multi-dermatomal herpes zoster 1, 2
- Visceral organ involvement 1
- CNS complications 1
- Complicated ocular disease 1
- Severely immunocompromised patients (active chemotherapy, HIV with low CD4 counts) 1, 2
Continue IV therapy for minimum 7-10 days until clinical resolution, then switch to oral therapy to complete the treatment course. 2 Monitor renal function closely during IV acyclovir, with dose adjustments for renal impairment. 1
Special Population Considerations
Immunocompromised Patients:
All immunocompromised patients require antiviral treatment regardless of timing. 2 Consider temporary reduction or discontinuation of immunosuppressive medications in cases of disseminated or invasive disease, restarting only after commencing anti-VZV therapy and resolution of skin vesicles. 1, 2
Renal Impairment:
Mandatory dose adjustments based on creatinine clearance to prevent acute renal failure. 1, 4 For famciclovir with CrCl 20-39 mL/min: reduce to 500 mg every 24 hours. 4
Critical Pitfalls to Avoid
- Never use topical antivirals for shingles—they are substantially less effective than systemic therapy and not recommended. 1, 5
- 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 genital herpes regimens (e.g., acyclovir 400 mg three times daily)—these are inadequate for VZV infection. 1
- Avoid corticosteroids in immunocompromised patients due to increased risk of disseminated infection. 1
Acyclovir-Resistant Cases
For proven or suspected acyclovir-resistant herpes zoster, switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution. 1, 2 All acyclovir-resistant strains are also resistant to valacyclovir and most to famciclovir. 1 Suspect resistance if lesions fail to resolve within 7-10 days despite adequate therapy; obtain viral culture with susceptibility testing. 1