Moderate
Suspected
Description
Acyclovir has been associated with reduced phenytoin plasma concentrations in some patients, potentially compromising seizure control during antiviral therapy.
Mechanism
The precise mechanism is unclear; proposed explanations include increased renal or hepatic clearance of phenytoin, altered protein binding, or impaired absorption during GI side effects of acyclovir.
Clinical Significance
Case reports document breakthrough seizures with low phenytoin levels during acyclovir treatment; the interaction is not universally observed.
Management
Monitor phenytoin levels during and after acyclovir courses in patients with epilepsy; increase monitoring frequency if seizure threshold changes.