In an adult with shingles, what clinical criteria determine whether to use oral acyclovir versus intravenous acyclovir?

Deciding Oral vs IV Acyclovir in Varicella Zoster (Shingles)

For uncomplicated shingles in immunocompetent adults, oral acyclovir (800 mg five times daily for 7-10 days) is the appropriate first-line treatment, while intravenous acyclovir (10 mg/kg every 8 hours) is reserved for disseminated disease, severe immunosuppression, CNS complications, or complicated ocular/facial involvement. 1

Clinical Criteria for Oral Acyclovir

Use oral acyclovir when ALL of the following are present:

• Immunocompetent patient (no active chemotherapy, HIV with adequate CD4 count, no organ transplant, not on chronic high-dose immunosuppression) 1
• Localized dermatomal distribution (involvement of 1-2 contiguous dermatomes only) 1
• No visceral organ involvement (no hepatitis, pneumonia, or encephalitis) 1
• Able to take oral medications and maintain adequate hydration 2
• No CNS complications (no meningitis, encephalitis, or Guillain-Barré syndrome) 1

The standard oral regimen is acyclovir 800 mg five times daily for 7-10 days, initiated within 72 hours of rash onset for optimal efficacy. 3, 4 Treatment should continue until all lesions have completely scabbed, not just for an arbitrary 7-day period. 1

Absolute Indications for IV Acyclovir

Switch to or initiate IV acyclovir (10 mg/kg every 8 hours) when ANY of the following are present:

Disseminated Disease

• ≥3 dermatomes involved (multi-dermatomal distribution) 1
• Hemorrhagic or necrotic lesions 1
• Visceral organ involvement: hepatitis (elevated transaminases), pneumonia (respiratory symptoms), or other organ systems 1

Severe Immunosuppression

• Active chemotherapy (particularly with agents like daratumumab, bortezomib, or B-cell depleting therapies) 1
• HIV infection with low CD4 count 1
• Solid organ or bone marrow transplant recipients 1
• Chronic high-dose corticosteroids (>40 mg prednisone daily equivalent) 1
• Biologic immunosuppressants (anti-TNF agents, JAK inhibitors, rituximab) 1

Complicated Disease

• CNS involvement: encephalitis, meningitis, myelitis, or Guillain-Barré syndrome 1
• Complicated ocular disease: suspected intraocular involvement, retinal necrosis, or acute retinal necrosis syndrome 1
• Severe facial zoster with concern for cranial nerve involvement or potential CNS extension 1

Treatment Failure

• Lesions not improving after 7-10 days of oral therapy (suspect acyclovir resistance and obtain viral culture with susceptibility testing) 1
• New lesions continuing to form beyond 7 days of adequate oral antiviral therapy 1

Special Populations Requiring IV Therapy

Pregnant Women

• Serious viral-mediated complications such as pneumonia warrant IV acyclovir despite pregnancy Category B classification 3
• Uncomplicated dermatomal shingles in pregnancy can be treated with oral acyclovir, though data are limited 3

Immunocompromised Patients

• Even uncomplicated-appearing shingles in severely immunocompromised hosts (active chemotherapy, multiple myeloma on proteasome inhibitors) should receive IV acyclovir due to high dissemination risk 1
• Temporary reduction in immunosuppressive medications should be considered when clinically feasible in patients with disseminated or invasive disease 1

Dosing and Duration

Oral Acyclovir

• Standard dose: 800 mg orally five times daily 3, 2, 4
• Duration: 7-10 days, continuing until all lesions have completely scabbed 1
• Timing: Initiate within 72 hours of rash onset; efficacy drops substantially after this window 3, 4

IV Acyclovir

• Standard dose: 10 mg/kg IV every 8 hours 1, 2
• Duration: Minimum 7-10 days and until clinical resolution (all lesions scabbed, fever resolved) 1
• Renal dosing required: Adjust for creatinine clearance to prevent crystalluria and acute renal failure 1

Critical Monitoring Parameters

For IV Acyclovir

• Baseline renal function before initiation 1
• Weekly renal function monitoring during treatment 1
• Adequate hydration and urine output to prevent acyclovir crystalluria 2
• Mental status monitoring for neurotoxicity (confusion, hallucinations, tremors) 2
• Assessment for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose therapy 1

For Oral Acyclovir

• Adequate hydration throughout treatment 2
• Clinical improvement expected within 48-72 hours of initiating therapy 1
• Monitor for treatment failure: if lesions continue to form or fail to improve by 7-10 days, suspect resistance 1

Common Pitfalls to Avoid

• Do not use topical acyclovir for shingles—it is substantially less effective than systemic therapy 3, 1
• Do not stop treatment at exactly 7 days if lesions have not completely scabbed; continue until clinical endpoint is reached 1
• Do not use genital herpes dosing (400 mg TID) for shingles—this is inadequate for VZV infection 1
• Do not delay IV therapy in immunocompromised patients with seemingly localized disease—they require immediate escalation 1
• Do not confuse varicella (chickenpox) treatment window (24 hours) with herpes zoster treatment window (72 hours) 3

Acyclovir-Resistant VZV

If lesions fail to respond after 7-10 days of adequate therapy:

• Obtain viral culture with susceptibility testing 1
• Switch to foscarnet 40 mg/kg IV every 8 hours until clinical resolution for confirmed resistance 1
• Resistance is rare in immunocompetent patients but occurs in up to 7% of immunocompromised patients 1