Serum
phenobarbital levels can be increased by sodium
valproate. Small reductions in sodium
valproate levels have also been reported.
Valproate has been reported to cause increases, decreases, and no change in
serum primidone levels. Primidone-derived
phenobarbital levels appear to be increased by
valproate. Combined use of
phenobarbital and
valproate may cause an increase in
serum liver enzymes.
Use of this combination may result in excessive sedation and lethargy. To
control this interaction the dosage of
phenobarbital has been reduced by about 30 to 50%, without loss of seizure
control. Indicators of
phenobarbital toxicity include drowsiness, ataxia or dysarthria. Monitor levels as necessary.
Valproate has been associated with serious hepatotoxicity, especially in children aged less than 3 years, and this has been more common in those receiving other antiepileptics.
Valproate monotherapy is to be preferred in this group.