The “Forgotten” Cross‐Tolerance Between Phenobarbital and Primidone: It Can Prevent Acute Primidone‐Related Toxicity

Summary Purpose: We report on the effect that pretreating patients with phenobarbital has on averting adverse events when primidone is introduced. Methods: Thirty patients with intractable partial epilepsy were pretreated with phenobarbital before starting primidone. Therapy with primidone was started at a dosage of 500 mg/day, and the phenobarbital was stopped. The primidone dose was then increased by 125 to 250 mg every 3 weeks until adverse events or a seizure‐free state was reached. All previous antiep‐ileptic medications were tapered down to yield a primidone monotherapy regimen. Results: Twenty‐six patients (87%) tolerated the introduction of primidone with minimal or no adverse events. Only one patient had to discontinue primidone during the initial 4 weeks because of severe dizziness. This was the only patient in whom primidone monotherapy could not be reached because of adverse events. Three other patients experienced dizziness severe enough to interfere with their activities. This symptom disappeared in two patients after the dose was lowered; in the other patient, primidone was stopped and phenobarbital was restarted for another 4 days. No symptoms recurred when primidone was reintroduced on the fifth day. Conclusions: Pretreatment with phenobarbital can minimize the occurrence of intolerable adverse events associated with the introduction of primidone.