What are the first‑line medications for treating an acute episode of herpes zoster in an otherwise healthy adult?

First-Line Medications for Acute Herpes Zoster in Healthy Adults

For an otherwise healthy adult with acute herpes zoster, oral valacyclovir 1 gram three times daily for 7–10 days is the preferred first-line treatment, offering superior convenience and pain reduction compared to acyclovir. 1

Primary Antiviral Options

The three FDA-approved oral antivirals for herpes zoster are:

• Valacyclovir 1 gram three times daily for 7–10 days – This is the preferred first-line agent due to superior bioavailability, less frequent dosing (which improves adherence), and demonstrated superiority in reducing the duration of zoster-associated pain compared to acyclovir. 1, 2, 3

• Famciclovir 500 mg three times daily for 7 days – Equally effective to valacyclovir with better bioavailability than acyclovir, offering comparable pain reduction and lesion healing. 1, 4, 3

• Acyclovir 800 mg five times daily for 7–10 days – Remains an effective option but requires more frequent dosing (five times daily), which may reduce patient compliance. 1, 5, 6

Critical Treatment Parameters

Timing of Initiation

• Treatment must be started within 72 hours of rash onset for optimal efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1, 7, 8
• Treatment initiated between 48–72 hours still provides significant benefit, though earlier is better. 7
• Some observational data suggest benefit even beyond 72 hours, but the drug should ideally be given as soon as possible. 3

Duration Endpoint

• Continue treatment until all lesions have completely scabbed, not merely for an arbitrary 7-day period. 1, 5, 7
• The clinical endpoint of complete scabbing is more important than calendar days. 1

Comparative Efficacy

Valacyclovir and famciclovir demonstrate superior outcomes to acyclovir in several key parameters:

• Both newer agents reduce the duration of postherpetic neuralgia by approximately 2 months compared to placebo. 4
• Valacyclovir alleviates zoster-associated pain and postherpetic neuralgia significantly faster than acyclovir in head-to-head trials. 3
• The median duration of pain after healing was 40 days with valacyclovir versus 59 days with acyclovir in patients over 50 years. 2
• Famciclovir accelerates resolution of postherpetic neuralgia approximately twofold faster than placebo. 4

Common Pitfalls to Avoid

• Never use topical acyclovir – Topical antiviral therapy is substantially less effective than systemic therapy and is not recommended for shingles. 1

• Do not use genital herpes dosing – Acyclovir 400 mg three times daily is only appropriate for genital herpes or HSV suppression, not for shingles, which requires 800 mg five times daily. 1

• Do not stop at exactly 7 days – If lesions are still forming or have not completely scabbed, continue therapy until the clinical endpoint is reached. 1, 5

• Avoid premature discontinuation – Short-course therapy designed for genital herpes (1–3 days) is inadequate for varicella-zoster infection. 1

When to Escalate to Intravenous Therapy

While oral therapy is first-line for uncomplicated herpes zoster in healthy adults, intravenous acyclovir 10 mg/kg every 8 hours is required for: 1, 5

• Disseminated disease (≥3 dermatomes, visceral involvement, or hemorrhagic lesions)
• Complicated facial zoster with suspected CNS involvement or severe ophthalmic disease
• Treatment failure (lesions not improving after 7–10 days of adequate oral therapy)

Safety Profile

All three oral antivirals are well tolerated with similar adverse event profiles: 1, 4, 3

• Nausea and headache are the most commonly reported side effects
• Renal dose adjustment is mandatory for patients with renal impairment to prevent acute renal failure 1
• Adequate hydration should be maintained during therapy to reduce the risk of crystalluria 1