Development of tolerance to the side effects of primidone

Side effects and antiepileptic drug levels were measured during initiation of and chronic treatment with primidone (PRM). A significant change in the toxicity/serum level ratio was observed 6 h after the initial PRM dose. The amount of toxicity manifested by patients receiving PRM as their initial antiepileptic drug was not different from that of those patients previously treated with phenytoin (PHT) or carbamazepine (CBZ). These findings indicate rapid development of functional tolerance to side effects of PRM, which is not altered by previous exposure to PHT or CBZ. Phenobarbital pretreatment appears to produce cross-tolerance to the effects of PRM.