Valacyclovir (Valtrex) is Preferred Over Acyclovir for Shingles
Valacyclovir 1 gram three times daily for 7-10 days is the preferred first-line treatment for shingles in immunocompetent adults, offering superior convenience with equivalent or better efficacy compared to acyclovir. 1, 2
Why Valacyclovir is Superior
Dosing Convenience and Compliance
- Valacyclovir requires only 3 doses per day (1000 mg three times daily) compared to acyclovir's 5 doses per day (800 mg five times daily), making it significantly more convenient and likely to improve adherence 1, 3, 4
- The twice-daily dosing option (1.5 g twice daily) has been shown equally safe and effective as three-times-daily dosing, further enhancing compliance 5
Pain Resolution Advantage
- Valacyclovir alleviates zoster-associated pain and postherpetic neuralgia significantly faster than acyclovir, which is the most clinically meaningful outcome for patients 3, 4
- Both agents demonstrate similar efficacy for cutaneous healing, but valacyclovir's superior pain control makes it the better choice 3, 6
Bioavailability
- Valacyclovir achieves acyclovir exposures 3-5 times higher than oral acyclovir due to superior absorption, translating to better tissue penetration 7
Treatment Algorithm
Standard Immunocompetent Patients
- First-line: Valacyclovir 1 gram orally three times daily for 7-10 days 1, 2
- Alternative: Valacyclovir 1.5 grams twice daily for 7 days 5
- Continue treatment until all lesions have completely scabbed, not just for an arbitrary 7-day period 1
- Initiate within 72 hours of rash onset for optimal efficacy, though benefit may extend beyond this window 2, 3
When Acyclovir is Acceptable
- Acyclovir 800 mg orally 5 times daily for 7-10 days is acceptable if valacyclovir is unavailable or cost-prohibitive 1, 8
- Both FDA-approved for herpes zoster treatment 2, 8
Immunocompromised Patients
- Intravenous acyclovir 10 mg/kg every 8 hours is required for disseminated or invasive herpes zoster, not oral therapy 1
- Consider temporary reduction in immunosuppressive medications 1
- Treatment duration extends beyond standard 7-10 days as lesions develop over 7-14 days and heal more slowly 9
Critical Treatment Endpoints
- The key clinical endpoint is complete scabbing of all lesions, not calendar days 1
- Monitor for new lesion formation—immunocompetent patients typically stop forming new lesions after 4-6 days, while immunocompromised patients may continue for 7-14 days 9
Important Caveats
What NOT to Do
- Never use topical acyclovir—it is substantially less effective than oral therapy 1, 9
- Do not use the 400 mg three-times-daily acyclovir dose for shingles; this is only appropriate for genital herpes or HSV suppression 1
- Avoid valacyclovir 8 g/day in immunocompromised patients due to risk of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura 9
Renal Dosing
- Dose adjustments are mandatory for renal impairment to prevent acute renal failure 1
- Monitor renal function closely during IV acyclovir therapy 1
Special Populations
- Facial zoster requires particular urgency due to risk of ophthalmic and cranial nerve complications—initiate treatment immediately 1
- Pregnant women exposed to VZV should receive varicella zoster immune globulin within 96 hours 1
Safety Profile
- Both valacyclovir and acyclovir are well tolerated with similar adverse event profiles 10, 3, 4
- Most common side effects: headache and nausea, occurring in <10% of patients 10, 6
- No serious adverse events reported in clinical trials comparing the two agents 10
- Resistance remains rare (<0.5%) in immunocompetent hosts 10