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Primidone (Mysoline)

Primidone was introduced about 40 years ago. Since then, several more effective and less toxic antiepileptic drugs have been introduced. The principal use of primidone is control of grand mal, psychomotor and focal epileptic seizures. Primidone is metabolized to phenobarbital and phenylethylmalonamide (PEMA). Both metabolites contribute to its therapeutic effect. The half-life of primidone is 8 to 22 hours, while phenobarbital is about 70 hours. Phenobarbital levels should be measured anytime a primidone level is requested. Steady state levels are reached 16 to 60 hours after initiating therapy in adults and 20 to 30 hours in children. Hepatocellular disease, renal impairment, valproic acid and isoniazid increase primidone levels.

Primidone is dosed to achieve a serum concentration similar to that desired for phenobarbital alone (15 - 40 ug/mL).The therapeutic range of primidone is 7 to 10 ug/mL in children and 9.0 to 12.5 ug/mL in adults. Levels >15.0 ug/mL are considered toxic. Therapeutic phenobarbital concentration is 15 - 30 ug/mL in infants and children and 20 - 40 ug/mL in adults. Levels >55 ug/mL are considered toxic.

The primidone to phenobarbital ratio is variable depending on the duration of primidone administration. If a patient is noncompliant and starts primidone medication just before his/her visit to the doctor, the ratio will be high because not enough time has elapsed for phenobarbital to accumulate.

Specimen requirement is one lavender top (EDTA) tube of blood. Trough levels should be drawn immediately before the next dose.

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