Monitoring serum concentrations of topiramate
Assessing potential toxicity
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Topiramate is a broad spectrum, antiepileptic drug used 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 cotherapy 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.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Depends on clinical use:
Anticonvulsant: 5.0-20.0 mcg/mL
Psychiatric: 2.0-8.0 mcg/mL
Most individuals display optimal response to topiramate with serum levels 5.0 to 20.0 mcg/mL when used to control seizures. 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.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test cannot be performed on whole blood.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Hiemke C, Baumann P, Bergemann N, et al: AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: Update 2011. Pharmacopsychiatry 2011;44:195-235
2. 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
3. Johannessen SI, Tomsom T: Pharmacokinetic variability of newer antiepileptic drugs: when is monitoring needed? Clin Pharmacokinet 2006;45(11):1061-1075
4. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood, DE Bruns. Saunders, 2012