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Levetiracetam is approved for treatment of partial, myoclonic, and tonic-clonic seizures, and is used off-label for manic states and migraine prophylaxis. Levetiracetam has very favorable pharmacokinetics with good bioavailability and rapid achievement of steady state. Its hepatic metabolism is minimal and nonoxidative, making it safe for use with hepatic enzyme inducers or inhibitors. The major metabolite is a carboxylic acid derivate, which is inactive and accounts for roughly one quarter of the administered dose. Levetiracetam is excreted renally, with a mean half-life of 7 hours in adults and slightly less than that in children. Renal dysfunction may warrant therapeutic monitoring and/or dose adjustment.
Given the lack of drug interactions and favorably pharmacokinetics, the primary uses for therapeutic drug monitoring of levetiracetam are compliance assurance and management of physiological changes such as puberty, pregnancy, and aging. Toxicities associated with levetiracetam use include decreased hematocrit and red blood cell count, decreased neutrophil count, somnolence, asthenia, and dizziness. These toxicities may be associated with blood concentrations in the therapeutic range.
Monitoring serum concentration of levetiracetam, particularly in patients with renal disease
Assessing potential toxicity
Most individuals display optimal response to levetiracetam with serum levels 12 to 46 mcg/mL. Some individuals may respond well outside of this range, or may display toxicity within the therapeutic range; thus, interpretation should include clinical evaluation. Toxic levels have not been well established. Therapeutic ranges are based on specimen drawn at trough (ie, immediately before the next dose).
This test cannot be performed on whole blood.
1. Patsalos PN, Berry DJ, Bourgeois BF, et al: Antiepileptic drugs-best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring. ILAE Commission on Therapeutic Strategies. Epilepsia 2008 Jul;49(7):1239-1276
2. Johannessen SI, Tomson T: Pharmacokinetic variability of newer antiepileptic drugs: when is monitoring needed? Clin Pharmacokinet 2006;45(11):1061-1075