Antiepileptic drug therapy: Clinical laboratory significance

Pharmacotherapy Overview of Seizure Management in the Adult Emergency Department

“…After the phenytoin or fosphenytoin loading dose is administered, the maintenance phenytoin dose should be initiated within 8 to 12 hours of IV loading doses and within 12 to 24 hours after oral loading doses to maintain therapeutic serum concentrations. 37,38 An appropriate initial maintenance dose for phenytoin is 4 to 5 mg/kg/d in 2 to 3 divided doses. 39 For average-sized individuals, the maintenance dose is initiated at 100 mg orally 3 times daily.…”

“…In patients who are able to tolerate oral medications, oral valproate loading doses may cause severe nausea and vomiting. 38,50 In one study of 16 pediatric patients, a single oral loading dose of divalproex 15 mg/kg resulted in mild nausea in 3 (19%) of the patients and 1 episode of vomiting. 56 If valproate loading is administered orally, patients may experience less nausea and vomiting if it is administered in at least 2 divided doses separated by approximately 2 to 3 hours.…”

“…Calculation of the loading doses in patients with measurable yet subtherapeutic serum concentrations can be done with the following equation, although no correlation between serum valproate concentration and seizure control has ever been established: loading dose (mg) = [weight (kg) × Vd × (serum concentration desired -serum concentration measured (mg/L))]. 38,55 The Vd of valproate is 0.22 L/kg.…”

“…While therapeutic ranges for anticonvulsant drugs have been determined, there is significant interpatient variability in efficacy and toxicity within the therapeutic range for each drug. 38 While some patients may require dose titration to the higher end of the therapeutic range, others may be controlled at concentrations below the therapeutic range. In addition, some patients may experience adverse effects at therapeutic serum concentrations.…”

“…For example, valproate serum concentrations fluctuate throughout the day, often with no alteration in drug efficacy. 38 For certain drugs that are highly protein bound, such as phenytoin, obtaining free concentrations may be warranted in patients with conditions known to affect protein binding such as hypoalbuminemia, uremia, pregnancy, hyperbilirubinemia, liver disease, and concomitant medications that may competitively bind to albumin or affect the drug assay. 38 However, 10% to 15% of patients will have a free phenytoin concentration outside the predicted range without any identifiable cause.…”