|Values are valid only on day of printing.|
Monitoring serum concentrations of topiramate, particularly in patients with renal disease or those coadministered phenytoin or carbamazepine
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 sodium channels, potentiates gamma-aminobutyric acid (GABA) activity, and inhibits potentiation of the glutamate receptor, allowing the drug to block seizure spread. Topiramate shows favorable pharmacokinetics, with good absorption, low protein binding, and minimal metabolism. Elimination is predominantly renal as unaltered topiramate, with an elimination half-life of 20 to 30 hours.
Serum concentrations of other anticonvulsant drugs are not significantly affected by the concurrent administration of topiramate, with exception in individual patients on phenytoin exhibiting increased phenytoin plasma concentrations after addition of topiramate. Coadministration of phenytoin or carbamazepine decreases topiramate serum concentrations. Changes in co-therapy with phenytoin or carbamazepine for patients stabilized on topiramate therapy may require dose adjustment due to these instructions; therapeutic drug monitoring can assist this. As with other renally eliminated anticonvulsant drugs, patients with impaired renal function exhibit decreased topiramate clearance.
Most individuals display optimal response to topiramate with serum levels 2.0 to 20.0 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.
Toxic levels have not been well established.
Therapeutic ranges are based on specimens drawn at trough (ie, immediately before the next dose).
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.
1. Patslos 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, Tomsom T: Pharmacokinetic variablility of newer antiepileptic drugs: when is monitoring needed? Clin Pharmacokinet 2006;45(11):1061-1075
3. Snozek CL, Rollins LA, Peterson PW, Langman LJ: Comparison of a new serum topiramate immunoassay to fluorescence polarization immunoassay. Ther Drug Monit 2010 Feb;32(1):107-111