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Monitoring serum concentrations of topiramate
Assessing potential toxicity
Topiramate is a broad spectrum, anti-epileptic drug used to for various types of seizures, Lennox-Gastaut syndrome (a type of childhood onset epilepsy), and migraine prophylaxis. Topiramate blocks voltage-dependent sodium channels, potentiates gamma-aminobutyric acid (GABA) activity at some of the GABA receptors, and inhibits potentiation of the glutamate receptor and carbonic anhydrase enzyme which all contribute to its antiepileptic and antimigraine efficacy.
In general, topiramate shows favorable pharmacokinetics with good absorption (1-4 hours for the immediate-release formulation), low protein binding, and minimal hepatic metabolism. Elimination is predominantly renal and it is excreted unchanged in the urine with an elimination half-life of approximately 21 hours. As with other anticonvulsant drugs eliminated by the renal system, patients with impaired renal function exhibit decreased topiramate clearance and a prolonged elimination half-life.
Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of topiramate, with the exception of patients on phenytoin whose serum concentrations can increase after the addition of topiramate. Other drug-drug interactions include the coadministration of phenobarbital, phenytoin, or carbamazepine which can result in decreased topiramate concentrations. In addition, concurrent use of posaconazole and topiramate may result in the elevation of topiramate serum concentrations. Therefore, changes in co-therapy with these medications (phenytoin, carbamazepine, posaconazole, or phenobarbital) may require dose adjustment of topiramate and therapeutic drug monitoring could assist with this. The most common adverse drug effects associated with topiramate include: weight loss, loss of appetite, somnolence, dizziness, coordination problems, memory impairment, and paresthesia.
Most individuals display optimal response to topiramate with serum levels 2.0 to 8.0 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.
Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the next dose).
Toxic levels have not been well established.
This test cannot be performed on whole blood.
Serum must be separated from cells within 2 hours of drawing.
Specimens that are obtained from gel tubes are not acceptable.
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