What is the recommended frequency of acyclovir (antiviral medication) for an adult patient with a history of recurrent cold sores?

Acyclovir Dosing for Recurrent Cold Sores (Herpes Labialis)

For adults with recurrent cold sores, acyclovir 400 mg orally twice daily provides effective suppression when taken continuously, or 400 mg orally 5 times daily for 5 days when treating acute outbreaks. 1

Treatment Approach Based on Recurrence Frequency

For Infrequent Recurrences (Episodic Treatment)

• Initiate acyclovir 400 mg orally 5 times daily for 5 days at the first sign of prodrome (tingling, burning) 1
• Alternative regimen: 200 mg orally 5 times daily for 5 days, though less convenient 1
• Treatment must begin within 12 hours of symptom onset to achieve maximum benefit 1
• Mean duration of pain reduced from 3.9 days to 2.5 days with early treatment 1

For Frequent Recurrences (≥6 episodes/year)

• Chronic suppressive therapy: acyclovir 400 mg orally twice daily continuously 1, 2
• This regimen reduces clinical recurrences by 53% and virologically confirmed recurrences by 71% 2
• Median time to first recurrence extends from 46 days (placebo) to 118 days with suppression 2
• Continue suppressive therapy for 4 months, then reassess recurrence frequency 1, 2

Alternative Agents with Superior Convenience

While acyclovir remains effective, newer agents offer dramatically simplified dosing:

• Valacyclovir 2 g orally twice daily for 1 day reduces episode duration by 1.0 day compared to placebo 1, 3
• Famciclovir 1500 mg as a single dose significantly reduces healing time 1
• These single-day regimens improve adherence while maintaining equivalent or superior efficacy to 5-day acyclovir courses 1, 3

Critical Timing Considerations

Peak viral replication occurs within the first 24 hours after lesion onset, making immediate treatment initiation essential 4. Patients should:

• Keep medication readily available at home 1
• Begin treatment at the earliest prodromal symptoms (tingling, itching, burning) 1
• Do not wait for visible lesions to appear—efficacy drops substantially after 72 hours 1

Common Pitfalls to Avoid

• Topical acyclovir is substantially less effective than oral therapy and should not be used 5, 4
• The 5-times-daily dosing requirement for episodic treatment creates adherence challenges; consider valacyclovir or famciclovir for better compliance 1
• Acyclovir does not eradicate latent HSV-1 or prevent future recurrences after discontinuation of suppressive therapy 5, 4
• Patients often delay treatment waiting for "confirmation" of an outbreak—educate them to treat prodromal symptoms immediately 1

Safety and Monitoring

• Ensure adequate hydration throughout treatment to prevent acyclovir crystalluria 5, 4
• Toxicity with continuous suppressive therapy is minimal, and viral resistance during suppressive use has not been a clinical problem 6
• Expect clinical improvement within 48-72 hours of initiating therapy 5, 4

When Suppressive Therapy Fails

• If breakthrough recurrences occur on 400 mg twice daily, consider increasing to 400 mg three times daily 6
• For confirmed acyclovir-resistant HSV (rare in immunocompetent patients), switch to foscarnet 40 mg/kg IV three times daily 1, 5, 4