What is the dose of acyclovir (antiviral medication) for erythema multiforme?

Acyclovir Dosing for Erythema Multiforme

For herpes simplex virus-associated erythema multiforme, use acyclovir 400 mg orally twice daily as continuous suppressive therapy to prevent recurrent episodes. 1

Treatment Approach

Acute Episodes

• Acyclovir does NOT effectively treat active erythema multiforme lesions once they have developed 2
• Treatment of acute episodes with acyclovir at 25 mg/kg per day showed no reduction in episode duration in pediatric studies 2
• The pathophysiology involves an immune response to HSV antigens rather than active viral replication in the skin lesions, explaining why antiviral therapy during acute episodes is ineffective 3

Suppressive Therapy (The Recommended Approach)

The primary role of acyclovir in erythema multiforme is prevention through continuous suppressive therapy, not treatment of active episodes. 1

Standard Suppressive Regimen

• Acyclovir 400 mg orally twice daily continuously 1
• This regimen completely suppressed attacks in 7 of 11 patients (64%) in a placebo-controlled trial 1
• The median number of attacks was zero in the acyclovir group versus three in the placebo group (P < 0.0005) 1

Duration of Suppressive Therapy

• Initial treatment course: 6 months minimum 1
• Some patients may require longer courses (10-26 months) for sustained remission 4
• After 6 months, consider discontinuation to assess if remission has been induced 1
• If recurrence occurs after stopping, reinitiate suppressive therapy 3

Alternative Dosing Strategies

• Pediatric dosing: 20 mg/kg per day for prophylaxis (successfully prevented recurrences in 3 of 3 children during treatment) 2
• Some protocols use higher doses during prodromal HSV symptoms while maintaining baseline suppression 5

Clinical Algorithm

Step 1: Confirm HSV Association

• HSV IgG serology is positive in approximately 91% of recurrent erythema multiforme cases 3
• Even patients without obvious HSV lesions may have HSV DNA detectable in target lesions by PCR 2
• Consider HSV-associated even in "idiopathic" cases, as subclinical HSV may be the trigger 1

Step 2: Initiate Suppressive Therapy

• Start acyclovir 400 mg orally twice daily 1
• Continue for at least 6 months 1
• Monitor for complete suppression of erythema multiforme episodes 1

Step 3: Manage Partial or Non-Response

If erythema multiforme episodes continue despite acyclovir monotherapy:

• Add dapsone as combination therapy (used successfully in 9 of 33 patients with partial acyclovir response) 3
• Add thalidomide if dapsone causes adverse effects (used successfully in 4 of 33 patients) 3
• Consider immunosuppressants for refractory cases 3

Step 4: Long-Term Management

• After initial 6-month course, attempt discontinuation to assess for sustained remission 1
• If relapse occurs, reinitiate suppressive therapy 3
• Some patients require multiple cycles (2-6 additional cycles) over years 3
• Two of 11 patients achieved complete remission after acyclovir treatment, suggesting potential disease-modifying effects 1

Important Caveats

What Does NOT Work

• Topical acyclovir is ineffective for erythema multiforme prevention 2
• Treatment-dose acyclovir during acute episodes does not shorten duration of erythema multiforme lesions 2
• Oral steroids are generally unresponsive in HSV-associated erythema multiforme 2

Expected Timeline

• Erythema multiforme typically appears 10-14 days after HSV reactivation 4
• The mean time from HSV lesion to erythema multiforme onset is 3.9 days (range 0-11 days) 2
• Episodes last a mean of 10.6 days without treatment 2

Special Considerations

• Recurrent disease is common: patients average 2.6 episodes per year without suppression 2
• Sun exposure can precipitate episodes in children 2
• HSV-associated erythema multiforme does not progress to Stevens-Johnson syndrome 2
• Complete disease remission may occur in some patients after prolonged suppressive therapy 1