Is 400 mg PO (per oral) three times a day the correct dosing for acyclovir in treating herpes simplex virus infections?

Acyclovir 400 mg PO Five Times Daily Dosing

Yes, acyclovir 400 mg orally five times a day is correct dosing, but only for specific indications: first-episode herpes proctitis (10 days) or as an alternative high-dose regimen for immunocompromised patients with recurrent HSV. 1, 2

Standard Dosing for Common HSV Infections

For most herpes simplex virus infections, 400 mg five times daily is NOT the standard dose. The correct dosing depends on the clinical scenario:

First-Episode Genital Herpes

• Standard dose: 200 mg orally 5 times daily for 7-10 days 1, 3
• This is the FDA-approved and CDC-recommended regimen for initial genital herpes 1, 3

First-Episode Herpes Proctitis

• 400 mg orally 5 times daily for 10 days 1, 4
• This is the only standard indication where 400 mg five times daily is the recommended dose 1

Recurrent Genital Herpes Episodes

Three equivalent dosing options exist 1, 5, 4, 3:

• 200 mg orally 5 times daily for 5 days, OR
• 400 mg orally 3 times daily for 5 days, OR
• 800 mg orally 2 times daily for 5 days

The higher-dose, less-frequent regimens (400 mg TID or 800 mg BID) improve adherence while maintaining equivalent efficacy 4

Chronic Suppressive Therapy

• 400 mg orally 2 times daily for patients with ≥6 recurrences per year 1, 5, 3
• This reduces recurrence frequency by ≥75% 5

When 400 mg Five Times Daily May Be Appropriate

Immunocompromised Patients

• For AIDS patients with recurrent herpes, some experts recommend 400 mg five times daily for 5 days or until eruption clears, then step down to 400 mg three times daily for 1-2 months, followed by 400 mg twice daily for maintenance 2
• This aggressive initial dosing addresses the more severe and prolonged HSV disease seen in immunocompromised hosts 6, 2

Acyclovir-Resistant HSV (Treatment Failure)

• If standard oral acyclovir (200 mg five times daily) fails after 3-5 days, escalation to 800 mg five times daily should be attempted before switching to alternative agents 6
• If 800 mg five times daily fails after 5-7 days, the patient likely has acyclovir-resistant HSV and requires foscarnet 40 mg/kg IV three times daily or 60 mg/kg IV twice daily 1, 5, 6

Critical Pitfalls to Avoid

Common dosing errors:

• Confusing the 400 mg dose frequency: 400 mg is typically dosed 3 times daily (not 5 times daily) for recurrent episodes 1, 5, 4, 3
• Using 400 mg five times daily (2000 mg/day total) when 400 mg twice daily (800 mg/day total) is appropriate for suppression 1, 3
• Failing to adjust dosing in renal impairment—acyclovir requires dose modification when creatinine clearance <25 mL/min 3

Ensure adequate hydration throughout treatment to prevent acyclovir crystalluria, as the drug is primarily renally excreted 5, 4

Algorithm for Correct Acyclovir Dosing

For immunocompetent patients:

• First genital herpes → 200 mg 5x daily for 7-10 days 1, 3
• Herpes proctitis → 400 mg 5x daily for 10 days 1
• Recurrent episodes → 400 mg 3x daily (or 800 mg 2x daily) for 5 days 1, 5, 3
• Suppression → 400 mg 2x daily 1, 5, 3

For immunocompromised patients:

• Consider higher doses: 400 mg 3-5 times daily 5, 2
• Monitor for treatment failure suggesting resistance 5, 6