Primidone shares the toxic potentials of the barbiturate-derivative anticonvulsants, and the usual precautions of anticonvulsant therapy should be observed. Since primidone therapy is generally prolonged, the manufacturers recommend that a complete blood count and an SMA-12 test be performed every 6 months in patients receiving the drug.
Clinicians should inform patients, their families, and caregivers about the potential for an increased risk of suicidal thinking and behavior (suicidality) associated with antiepileptic therapy. For a complete discussion,
Serious adverse reactions to primidone are rare, but mild adverse effects occur frequently. The most common adverse effects are drowsiness, ataxia, vertigo, lethargy, anorexia, nausea, and vomiting; ataxia and vertigo tend to disappear with continued therapy or with reduction of initial dosage.
Occasionally, primidone may cause hyperexcitability (especially in children), which may include hyperirritability; however, it is usually less severe than that associated with phenobarbital. Rarely, primidone therapy has precipitated an acute psychosis-like reaction. Other adverse reactions reported during primidone therapy are fatigue, emotional disturbances, drowsiness, diplopia, nystagmus, morbilliform rash, alopecia, edema of the eyelids, leg edema, leukopenia, eosinophilia, impotence, a malignant lymphoma-like syndrome, and a syndrome resembling systemic lupus erythematosus, all of which subsided when the drug was discontinued. Megaloblastic anemia (which responds to folic acid therapy), red cell hypoplasia, or aplasia, granulocytopenia, and agranulocytosis have occurred rarely.
Safe use of primidone during pregnancy or lactation has not been established. Since primidone is apparently distributed into milk, nursing should be discontinued if excessive somnolence or drowsiness is observed in nursing infants of women receiving the drug.