Am. Kanner et al., The "forgotten" cross-tolerance between phenobarbital and primidone: It can prevent acute primidone-related toxicity, EPILEPSIA, 41(10), 2000, pp. 1310-1314
Purpose: We report on the effect that pretreating patients with phenobarbit
al 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 st
arted at a dosage of 500 mg/day, and the phenobarbital was stopped. The pri
midone dose was then:increased by 125 to 250 mgr every 3 weeks until advers
e events or a seizure-free state was reached. All previous antiepileptic me
dications 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 prim
idone 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.