The Annals of Pharmacotherapy ■ 2002 May, Volume 36 ■ 917 www.theannals.com REQUEST Should lamotrigine serum concentrations be used to adjust lamotrigine doses? RESPONSE BACKGROUND Therapeutic drug monitoring (TDM) refers to the prac- tice of monitoring drug concentrations in body fluids for the purposes of optimizing therapeutic efficacy and mini- mizing adverse effects. The therapeutic range is nothing more than a confidence interval; it is defined as the range of drug concentrations in which the probability of efficacy is high and the probability of toxicity is low. Thus, the therapeutic range for an individual patient may differ from the therapeutic range described for a population. In pedi- atric practice, TDM is frequently justified due to large in- terindividual pharmacokinetic variability. The continual maturation of body systems through infancy, childhood, and adulthood results in changing drug disposition over time. TDM has made significant contributions to the treat- ment of epilepsy. Currently, formal guidelines for TDM of lamotrigine do not exist. A decision-making algorithm 1 will be used to evaluate the clinical evidence to support or re- fute TDM of lamotrigine. LITERATURE REVIEW Is the patient receiving the best drug for his/her specific in- dication? Lamotrigine shows broad-spectrum efficacy against par- tial seizures, primarily and secondarily generalized tonic– clonic seizures, absence seizures, drop attacks associated with Lennox–Gastaut syndrome, and, possibly, other seizure types. 2 Its primary mechanism of action is blocking volt- age-dependent sodium channels, leading to inhibition of excitatory neurotransmitter release and stabilization of neuronal membranes. Lamotrigine is indicated as adjunc- tive or monotherapy. Can the drug be readily measured in the desired biological matrix? More than 20 HPLC assays are available for determina- tion of lamotrigine concentrations in serum. 3-8 There ap- pears to be no potential for direct chromatographic inter- ference by other drugs (e.g., phenobarbital, phenytoin, ethosuximide, valproic acid, theophylline, primidone, pro- cainamide, quinidine, carbamazepine, common tricyclic antidepressants, benzodiazepines, salicylate, acetaminophen) in these HPLC assays. 5,7 Immunofluorometric assays have also been developed. 8 Is the drug’s pharmacologic response not readily assess- able? Therapeutic response cannot be immediately measured because the use of lamotrigine is primarily prophylactic. Therapeutic Drug Monitoring of Lamotrigine Elaine Chong and L Lee Dupuis OBJECTIVE: To evaluate the usefulness of routine monitoring of serum lamotrigine concentration. DATA SOURCE: Literature was accessed through MEDLINE (1990–January 2001). Key search terms included lamotrigine, pharmacokinetics, and epilepsy. DATA SYNTHESIS: A decision-making algorithm was used to evaluate the clinical evidence to support or refute the routine use of serum lamotrigine concentrations to adjust doses. The value of serum lamotrigine concentration monitoring remains controversial, primarily because clear relationships between concentration and pharmacologic response (either efficacy or toxicity) have not been demonstrated. CONCLUSIONS: Serum concentration monitoring of lamotrigine is not recommended as a tool for routine dose adjustment. KEY WORDS: epilepsy, lamotrigine, pharmacokinetics. Ann Pharmacother 2002;36:917-20. Author information provided at the end of the text. by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from by guest on October 11, 2013 aop.sagepub.com Downloaded from