Primidone therapeutic range

Reference Analytical Number method of cases Plasma primidone ( xg/ml) Therapeutic range Toxicity Comments ... 

The major untoward effect of phenobarbital and primidone, when used as anticonvulsants, is sedation. Another side effect of considerable importance, particularly in children, is a possible disturbance in cognitive function. Even when the serum concentration is within the therapeutic range, apparently the ability to concentrate and perform simple tasks is decreased. 

With chronic exposure, side effects may include rash, thrombocytopenia, leukopenia, and a lupus-like disorder. Chronic therapy is likely to result in tolerance, and withdrawal symptoms if primidone therapy is abruptly stopped. Doses in excess of 1500 mg (twice the maximum recommended daily dose) should be considered toxic. Less common side effects are hypotension, hypothermia, and dermal bullae. Encephalopathy has been observed in an epileptic patient with high plasma levels and poor renal function. With plasma concentrations exceeding 80pgml primidone may precipitate and cause crystalluria. Plasma levels >10 rgpml are associated with toxic effects. The therapeutic range is reportedly 5-10pgml , but clinical effects correlate more closely with phenobarbital blood levels. 

The optimal therapeutic concentration of primidone has been established as 5 to 12 U,g/mL. Because phenobarbital is an active metabolite of primidone, concurrent analysis of phenobarbital is required for complete result interpretation. The previously defined therapeutic range for phenobarbital applies to adequate primidone therapy. The phenobarbital concentrations rise gradually over a period of 1 to 2 weeks after therapy is initiated. Toxicity due to accumulation of primidone occurs at serum concentrations in excess of 15 llg/mL and is usually associated with symptoms of sedation, nausea, vomiting, diplopia, dizziness, ataxia, and a phenobarbital concentration greater than dOpg/mL. Specimen collection is dictated by the same rules that apply to phenobarbital the trough concentration is most useful. 

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