Primidone

Nervous system

A woman who continued to take primidone after resection of an astrocytoma developed a hyperammonemic encephalopathy, with somnolence and asterixis; the symptoms resolved on withdrawal of the drug [ ].

Exacerbation of dementia has been attributed to sedation caused by primidone [ ].

Psychiatric

In 241 outpatients with epilepsy taking primidone depression was diagnosed in 103 (43%); associated factors included use of primidone and inadequate seizure control [ ].

Catatonic schizophrenia, following visual and auditory hallucinations, has been attributed to primidone in a severely retarded, 19-year-old woman, who had taken primidone 250 mg tds for 12 years [ ]. The primidone serum concentration was well above the usual target range and the symptoms abated after primidone was withdrawn and the serum concentration fell.

Hematologic

Thrombocytopenia has been attributed to primidone [ ].

Megaloblastic anemia associated with a low serum folic acid concentration has been reported during treatment with primidone [ ].

Immunologic

Giant cell myocarditis has been reported in a patient taking phenytoin, phenobarbital, and mephobarbital and in one taking primidone [ ].

An unusual case of allergy involved a 34-year-old woman who developed pruritic skin wheals after swallowing food that her daughter, after having taken primidone, had left on her plate [ ]. When the woman was challenged with oral primidone the wheals recurred.

Teratogenicity

Two girls were born with morphogenetic defects after their mothers had taken primidone during pregnancy; one had ocular hypertelorism, a wide anterior fontanelle, and pulmonic stenosis; the other had Fallot's tetralogy [ ]. However, the alternative diagnosis was Noonan’s syndrome [ ].

In 14 women with epilepsy who too primidone during pregnancy, either alone or in combination with other antiepileptic drugs, maternal serum concentrations of primidone and metabolites were generally low and the concentrations of its main metabolite, phenobarbital and phenylethylmalonamide (PEMA), fell within the first month; the phenobarbital/primidone ratio (mean 0.84) and PEMA/primidone ratio (mean 0.56) in pregnant patients were lower than in non-pregnant women, except when primidone was given in combination with phenytoin in which case the expected ratios were found [ ]. There was a ventricular septal defect in one child and five had microcephaly. There was a high incidence of poor somatic development, with dystrophy in three and short stature in two. Head circumferences and/or weights were below the 10th percentile in several children. Four had marked facial dysmorphy.

In another case fetal exposure to primidone was associated with Goldenhar syndrome, hemifacial microsomia, Fallot’s tetralogy, aqueductal stenosis, and anterior encephalocele in a male infant [ ].

Liver disease

The half-life and the apparent clearance of unchanged primidone after a single oral dose of 500 mg were not altered in seven patients with acute viral hepatitis compared with seven healthy subjects, although the serum concentrations of the metabolites phenobarbital and phenylethylmalonamide were low or undetectable in the patients [ ]. The authors thought that accumulation of primidone and consequent toxicity were unlikely to occur in patients who develop acute viral hepatitis, despite evidence that primidone metabolism is reduced.