What is the role of primidone in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
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Primidone is metabolized to PHB and phenylethylmalonamide (PEMA). Its main action is through the derived PHB. The real clinical effect of primidone or PEMA is unknown and controversial.

Primidone is absorbed orally. Bioavailability is close to 100%, with a peak level after 3 hours. Plasma protein binding is only 25%. Elimination half-life is 5-18 hours, but that of the derived PHB is 75-120 hours. Primidone is metabolized by the cytochrome oxidase system; therefore, it is affected by enzyme inducers, including PHB itself. The levels of primidone seldom are useful for monitoring efficacy, and range from 5-12 mg/L. The PHB level is the same as the level when PHB is administered directly (15-40 mg/L).

Primidone has the same indications as PHB. It is available in tablets of 50 mg and 250 mg and suspension of 250 mg/5 mL; 250 mg of primidone is equivalent to 60 mg of PHB. The average therapeutic doses range from 500-1500 mg.

The major adverse effects of primidone are intense sedation, dizziness, and nausea at the onset of treatment, most likely secondary to administration of the parental drug. These effects usually clear after 1 week of treatment. A very low dose is recommended at the onset of treatment. Other effects are the same as those of PHB.

Primidone can be used for partial onset and secondarily generalized seizures. However, it is a second-line agent because of its side-effect profile, which is similar to that of PHB. It has been useful in the treatment of essential tremor at low doses.

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