Timing of Acyclovir Initiation in Shingles
Acyclovir should ideally be started within 72 hours of rash onset for optimal efficacy, but treatment initiated after 72 hours may still provide benefit for zoster-associated pain and should not be withheld, particularly in high-risk patients. 1
The 72-Hour Window: Standard Recommendation
- The 72-hour cutoff represents the traditional threshold for maximum antiviral efficacy in reducing acute pain, accelerating lesion healing, and preventing postherpetic neuralgia. 1
- Treatment initiated within 48 hours of rash onset provides the greatest benefit, with one study showing no significant hastening of rash healing when therapy was started later than 48 hours. 2
- Viral shedding peaks in the first 24 hours after lesion onset when most lesions are vesicular, making early intervention critical for blocking viral replication. 1
Evidence for Treatment Beyond 72 Hours
- A large observational study found that starting valacyclovir later than 72 hours after rash onset did not significantly reduce its beneficial effect on duration of zoster-associated pain, suggesting antiviral therapy may be effective when given later than previously thought. 3
- This finding challenges the rigid 72-hour cutoff and suggests a more nuanced approach, particularly for pain outcomes rather than purely cutaneous healing. 3
Clinical Decision Algorithm
When to treat beyond 72 hours:
- Continue antiviral therapy until all lesions have scabbed, which is the key clinical endpoint—not an arbitrary 7-day duration—and treatment should continue if lesions remain active beyond 7 days. 1
- New lesions are still forming (indicating active viral replication). 1
- Facial or ophthalmic involvement (higher risk of complications requiring urgent treatment regardless of timing). 1
- Immunocompromised status (lesions develop over 7-14 days and heal more slowly, requiring extended treatment). 1
- Multi-dermatomal or disseminated disease (requires IV acyclovir regardless of timing). 1
When treatment after 72 hours offers diminishing returns:
- Uncomplicated dermatomal shingles in young, healthy, immunocompetent patients where all lesions have already fully crusted. 2
- Mild cases in younger individuals who may not require antiviral treatment at all. 4
Important Caveats
- The 72-hour window applies primarily to cutaneous healing endpoints; pain reduction may still benefit from later initiation. 3
- Treatment duration should be guided by lesion healing, not calendar days—continue until all lesions have completely scabbed. 1
- Immunocompromised patients may require treatment extension well beyond 7-10 days as their lesions continue to develop over longer periods (7-14 days) and heal more slowly. 1
- Standard dosing is acyclovir 800 mg five times daily for 7-10 days, or valacyclovir 1000 mg three times daily for 7 days (better bioavailability and adherence). 1, 3
Common Pitfalls to Avoid
- Rigidly refusing treatment after 72 hours when patients may still benefit, particularly for pain outcomes and in high-risk populations. 3
- Stopping treatment at exactly 7 days when lesions are still forming or have not completely scabbed. 1
- Failing to escalate to IV acyclovir in immunocompromised patients or those with disseminated disease, regardless of timing. 1
- Using the short-course genital herpes dosing (400 mg three times daily) instead of the higher VZV-appropriate dose (800 mg five times daily). 1