Primidone, used alone or in combination with other anticonvulsants, is indicated for the control of generalized tonic-clonic (grand mal), psychomotor, and focal seizures. It may also be effective in controlling grand mal seizures that are resistant to other anticonvulsant therapies.

Primidone increases the seizure threshold induced by electrical or chemical stimulation and may modify seizure patterns in experimental animals. The exact mechanism of its antiepileptic action is not fully understood. Primidone itself has anticonvulsant activity, and its metabolites—phenobarbital and phenylethylmalonamide (PEMA)—also contribute to this effect. In addition, PEMA enhances the anticonvulsant activity of phenobarbital in experimental studies.

Patients 8 years of age and older who have received no previous treatment may be started on primidone according to the following regimen using either 50 mg or scored 250 mg primidone tablets:

• Days 1 to 3: 100 to 125 mg at bedtime.
• Days 4 to 6: 100 to 125 mg twice a day.
• Days 7 to 9: 100 to 125 mg three times a day.
• Day 10 to maintenance: 250 mg three times a day.

For most adults and children 8 years of age and over, the usual maintenance dosage is three to four 250 mg primidone tablets in divided doses (250 mg three times a day or four times a day). If required, an increase to five or six 250 mg tablets daily may be made, but daily doses should not exceed 500 mg four times a day.

Dosage should be individualized to provide maximum benefit. In some cases, serum blood level determinations of primidone may be necessary for optimal dosage adjustment. The clinically effective serum level for primidone is between 5 to 12 mcg/mL.

The most common early side effects are ataxia and vertigo, which usually diminish with continued therapy or dose reduction. Occasionally reported adverse effects include nausea, loss of appetite (anorexia), vomiting, fatigue, hyperirritability, emotional disturbances, sexual impotence, diplopia, nystagmus, drowsiness, and morbilliform skin rash. Rare hematological reactions such as granulocytopenia, agranulocytosis, red-cell hypoplasia, and aplasia have been reported. These or other persistent or severe adverse effects may require discontinuation of the drug. Megaloblastic anemia may rarely occur as an idiosyncratic reaction to Primidone and other anticonvulsants, and it usually responds to folic acid without stopping therapy.

The effects of Primidone during human pregnancy and breastfeeding are not fully known. Evidence suggests that primidone is excreted in breast milk in significant amounts in treated mothers. Since detection of primidone in biological fluids is complex, excessive drowsiness or sedation in nursing infants may indicate that breastfeeding should be discontinued.

The total daily dose should not exceed 2 g. As Primidone therapy is usually long-term, complete blood counts and SMA-12 tests should be performed every 6 months for monitoring.

Adjunct anti-epileptic drugs

Store below 30°C, protected from light and moisture. Keep out of reach of children.