When should oral acyclovir be used versus intravenous acyclovir for varicella in healthy children, adolescents, adults, immunocompromised patients (e.g., human immunodeficiency virus infection with CD4 count less than 200 cells/µL, chemotherapy, organ transplant, primary immunodeficiency), neonates, pregnant women, or those with severe or disseminated disease, extensive cutaneous or mucosal involvement, or complications such as pneumonia, hepatitis, encephalitis, or inability to tolerate oral medication?

Oral vs IV Acyclovir for Varicella: Decision Algorithm

Use oral acyclovir for healthy adolescents (≥12 years), adults, and high-risk healthy children (chronic lung/skin disease, long-term salicylates) when treatment can start within 24 hours of rash onset; reserve IV acyclovir for immunocompromised patients, neonates, pregnant women with complications, and any patient with severe/disseminated disease or inability to take oral medication. 1, 2, 3

Decision Framework by Patient Population

Healthy Children (<12 years)

• Oral acyclovir is NOT routinely recommended for uncomplicated varicella in otherwise healthy children under 12 years, as the marginal benefit (1-day reduction in fever, 15-30% reduction in symptom severity) does not justify routine use 3
• Consider oral acyclovir (20 mg/kg four times daily, maximum 800 mg per dose, for 5 days) only if the child has chronic cutaneous disorders, chronic pulmonary disease, or receives long-term salicylate therapy 4, 1, 2
• Treatment must be initiated within 24 hours of rash onset to have any effect 4, 1

Healthy Adolescents (≥12 years) and Adults

• Oral acyclovir should be considered for all otherwise healthy persons aged >12 years, as they are at increased risk for moderate to severe varicella 4, 1
• Dosing: 800 mg orally four times daily for 5 days, initiated within 24 hours of rash onset 1, 2
• Delay beyond 24 hours results in loss of therapeutic effect 3

Immunocompromised Patients

• IV acyclovir is mandatory for all immunocompromised patients (HIV with CD4 <200, chemotherapy, organ transplant, primary immunodeficiency), regardless of timing of presentation 4, 1, 5
• Dosing: 1500 mg/m²/day IV divided into three doses (or 10 mg/kg IV every 8 hours) 6
• Sequential therapy may be considered: After minimum 48 hours of IV therapy, switch to oral acyclovir if patient is afebrile, has no new lesions for 24 hours, has no internal organ involvement, and can tolerate oral medications 6
• Continue treatment until all lesions have crusted over, not just for an arbitrary 7-10 days 1, 7
• Critical pitfall: Do not use oral acyclovir as initial therapy in immunocompromised patients, even if disease appears mild initially 5, 8

Neonates

• IV acyclovir is required for all neonates with varicella, particularly those born to mothers with varicella onset from 5 days before to 2 days after delivery (historical mortality 31% without intervention) 9, 5
• Preterm infants in the neonatal nursery and newborns during the first 2 weeks of life require IV therapy 5
• Do not use oral acyclovir in children younger than 2 years of age with varicella 5

Pregnant Women

• For mild, uncomplicated varicella: Oral acyclovir 800 mg five times daily for 5 days, initiated within 24 hours of rash onset 1, 9
• For serious complications (pneumonia, hepatitis, encephalitis): IV acyclovir is required 1, 9
• Acyclovir is FDA Category B in pregnancy, with registry data from 596 first-trimester exposures showing no increased birth defect rate compared to the general population (2.3% vs 3.2%) 9
• Post-exposure prophylaxis: Administer varicella-zoster immune globulin (VZIG) within 96 hours of exposure to seronegative pregnant women; VZIG prevents severe maternal disease but does NOT prevent viremia, fetal infection, or congenital varicella syndrome 9

Severe or Disseminated Disease (Any Patient)

• IV acyclovir is mandatory for varicella with complications including:
  • Pneumonia 1, 5, 8
  • Hepatitis 8
  • Encephalitis 8
  • Disseminated cutaneous disease 5, 8
  • Extensive mucosal involvement 8
• IV acyclovir is also required for patients unable to tolerate oral medication 8
• Continue IV therapy until clinical improvement is evident and all lesions have crusted 1, 7

Critical Timing Considerations

• The 24-hour window is absolute: Acyclovir (oral or IV) must be initiated within 24 hours of rash onset for healthy patients to achieve therapeutic benefit 4, 1, 3
• Exception: Immunocompromised patients should receive IV acyclovir regardless of timing, as they remain at risk for dissemination even with delayed presentation 1, 8

Common Pitfalls to Avoid

• Do not delay treatment waiting for laboratory confirmation in high-risk patients; clinical diagnosis is sufficient to initiate therapy 5, 8
• Do not use oral acyclovir as initial therapy in immunocompromised patients, even if they appear stable 5, 8
• Do not use oral acyclovir in children under 2 years of age, even if they are otherwise healthy 5
• Do not assume acyclovir prevents transmission or reduces school absence duration; isolation precautions must continue until all lesions are crusted 4, 1
• Do not withhold neonatal VZIG even if the mother received VZIG, when maternal rash occurs in the peripartum risk period (5 days before to 2 days after delivery) 9

Renal Dose Adjustments

For patients with renal impairment receiving oral acyclovir 800 mg four times daily 2:

• CrCl >25 mL/min: 800 mg every 4 hours (5 times daily)
• CrCl 10-25 mL/min: 800 mg every 8 hours
• CrCl 0-10 mL/min: 800 mg every 12 hours
• Hemodialysis: Administer additional dose after each dialysis session 2