Serious adverse reactions to primidone are rare, but mild adverse effects occur frequently. The most common are ataxia and vertigo, which often disappear with continued therapy, or possibly an initial dose reduction. Other adverse effects include drowsiness, lethargy, anorexia, fatigue, irritability, emotional lability, diplopia, nystagmus. Sedation and drowsiness also decrease with continued therapy or reduced dosage. GI reactions may be minimized by taking the drug with a large quantity of water or with food.
Sexual dysfunction includes libido decrease and impotence.
Granulocytopenia and red-cell hypoplasia and aplasia have been reported rarely. More rarely primidone causes anemia, or megaloblastic anemia, however anemia may respond to therapy with folic acid without discontinuing primidone therapy. CNS stimulation characterized by hyperexcitability can occur during therapy with primidone, especially in children. This reaction can exacerbate existing hyperexcitability and may require a change in medication. Prolonged use of barbiturates can produce physical dependence.