Therapeutic phenytoin levels are described as being 10 to 20 pg/mL (40 to 80 pmol/L), with a free phenytoin level of 1 to 2 pg/mL. 11 Although 50 percent of seizure patients achieve reduction of seizure frequency with amounts below these levels, some patients require levels above 20 pg/mL for adequate seizure control. The therapeutic range for phenytoin is rather narrow. However, some patients have a greater propensity for side effects than others. Individual variation in toxicity is a function of baseline neurologic status, individual response to the drug, and free drug fraction. Patients with underlying brain disease are predisposed to toxicity and may become toxic at low levels. Long-term therapy must be individualized and based on clinical response, drug levels, and signs of toxicity. In general, toxicity correlates fairly well with increasing plasma levels (Table 173-2), but this is not a universal tenet as some patients tolerate levels above 40 pg/mL quite well. Nystagmus usually appears first at a phenytoin level of 20 pg/mL but may occur at lower or higher levels. Almost all patients with phenytoin-induced seizures will have levels well above 30 pg/mL. Signs of toxicity occur at free phenytoin levels of 2.0 pg/mL and are consistently severe above 5.0 pg/mL.
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