{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:13:21Z","timestamp":1774311201836,"version":"3.50.1"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>The aim was to study the impact of therapeutic drug monitoring (TDM) on patients on lamotrigine (LTG) therapy and the evaluation of possible drug interactions, especially in triple antiepileptic drug combinations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>During the period of 2001\u20132014, 3118 predose samples were taken from 1137 patients &gt;15 years of age as part of their routine TDM. Drug interactions were evaluated using calculation of LTG clearance (CL).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Valproic acid (VPA) decreased LTG CL by 66% in bitherapy, and by 35% and 31% in triple therapy with carbamazepine (CBZ) and phenytoin (PHT), respectively. CBZ and PHT increased LTG CL by 52% and 96% in respective bitherapies but by 88% in triple therapy. Clonazepam, levetiracetam, and topiramate had no effect. The LTG therapeutic range (TR) was exceeded in 1% of cases in monotherapy, and in 4%\u20135% of cases in combination therapy. Only 54% of results were within the TR during 2001\u20132005, whereas 60%\u201362% were within the TR during 2006\u20132014. Adverse drug reactions (ADRs) were reported in 88 cases and occurred more frequently during TR during 2001\u20132005. Higher number of supratherapeutic levels in combination therapy led to a 3-fold higher incidence of ADR and poorer seizure control, as seizures occurred more often monthly (2.5%) or a few per year (41%) and fewer patients were seizure free (18%). Seizures occurred more often daily and monthly during the first period and in patients with 3 or 4 drugs in combination.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A significantly higher number of supratherapeutic levels were found in combinations with VPA, despite lower doses of LTG. Hepatic enzyme inducers, such as CBZ and PHT only partially compensated for the inhibitory effect of VPA. Decrease of both the frequency of seizures and the incidence of ADRs after TDM implementation suggests that TDM may have given clinicians the opportunity to achieve more optimal patient treatment.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000433","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T19:55:55Z","timestamp":1499370955000},"page":"543-549","source":"Crossref","is-referenced-by-count":15,"title":["Lamotrigine Drug Interactions in Combination Therapy and the Influence of Therapeutic Drug Monitoring on Clinical Outcomes of Adult Patients"],"prefix":"10.1097","volume":"39","author":[{"given":"Milan","family":"Grundmann","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blanka","family":"Koristkova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava; and"},{"name":"Clinical Pharmacology and"},{"name":"Laboratory Diagnostics, University Hospital Ostrava, Ostrava, Czech Republic."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Brozmanova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava; and"},{"name":"Clinical Pharmacology and"},{"name":"Laboratory Diagnostics, University Hospital Ostrava, Ostrava, Czech Republic."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Kacirova","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava; and"},{"name":"Clinical Pharmacology and"},{"name":"Laboratory Diagnostics, University Hospital Ostrava, Ostrava, Czech Republic."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230928","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/j.1528-1167.2011.03217.x","article-title":"The effect of age and comedication on lamotrigine clearance, tolerability, and efficacy","volume":"42","author":"Arif","year":"2011","journal-title":"Epilepsia."},{"key":"R2-20230928","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1007\/s40262-013-0088-z","article-title":"Drug interactions with the newer antiepileptic drugs (AEDs)\u2014Part 2: pharmacokinetic and pharmacodynamic interactions between AEDs and drugs used to treat non-epilepsy disorders","volume":"52","author":"Patsalos","year":"2013","journal-title":"Clin Pharmacokinet."},{"key":"R3-20230928","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF03191157","article-title":"Lamotrigine and valproate pharmacokinetics interactions in epileptic patients","volume":"34","author":"Lalic","year":"2009","journal-title":"Eur J Drug Metabol Pharmakokinet."},{"key":"R4-20230928","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/S1474-4422(03)00409-5","article-title":"Clinically important drug interactions in epilepsy: general features and interactions between antiepileptic drugs","volume":"2","author":"Patsalos","year":"2003","journal-title":"Lancet Neurol."},{"key":"R5-20230928","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/00007691-199904000-00006","article-title":"Lamotrigine drug interactions in a TDM material","volume":"21","author":"B\u00f6ttiger","year":"1999","journal-title":"Ther Drug Monit."},{"key":"R6-20230928","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1097\/00007691-200202000-00016","article-title":"New antiepileptic drugs: review on drug interaction","volume":"24","author":"Hachad","year":"2002","journal-title":"Ther Drug Monit."},{"key":"R7-20230928","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/00007691-200012000-00003","article-title":"Clinical study of lamotrigine and valproic acid in patients with epilepsy: using a drug interaction to advantage?","volume":"22","author":"Morris","year":"2000","journal-title":"Ther Drug Monit."},{"key":"R8-20230928","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.eplepsyres.2003.09.008","article-title":"Evaluation of VPA dose and concentration effects on lamotrigine pharmacokinetics: implications for conversion to lamotrigine monotherapy","volume":"57","author":"Gidal","year":"2003","journal-title":"Epilepsy Res."},{"key":"R9-20230928","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/00007691-199908000-00094","article-title":"Topiramate decreases lamotrigine concentrations [Abstract]","volume":"21","author":"Wnuk","year":"1999","journal-title":"Ther Drug Monit."},{"key":"R10-20230928","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1046\/j.1528-1157.2002.37701.x","article-title":"Lack of an effect of topiramate on lamotrigine serum concentrations","volume":"43","author":"Berry","year":"2002","journal-title":"Epilepsia."},{"key":"R11-20230928","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1046\/j.1528-1157.2003.64402.x","article-title":"Topiramate and lamotrigine pharmacokinetics during repetitive monotherapy and combination therapy in epilepsy patients","volume":"44","author":"Doose","year":"2003","journal-title":"Epilepsia."},{"key":"R12-20230928","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00228-007-0308-2","article-title":"Lamotrigine in children and adolescents: the impact of age on its serum concentrations and on the extent of drug interactions","volume":"63","author":"Reimers","year":"2007","journal-title":"Eur J Clin Pharmacol."},{"key":"R14-20230928","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1212\/01.WNL.0000138424.33979.0C","article-title":"Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy","volume":"63","author":"Hirsch","year":"2004","journal-title":"Neurology."},{"key":"R15-20230928","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1046\/j.1365-2125.1998.00835.x","article-title":"Lamotrigine and therapeutic drug monitoring: retrospective survey following the introduction of a routine service","volume":"46","author":"Morris","year":"1998","journal-title":"Br J Clin Pharmacol."},{"key":"R16-20230928","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.pediatrneurol.2012.08.002","article-title":"Lamotrigine serum concentration in children with epilepsy","volume":"47","author":"Heyman","year":"2012","journal-title":"Pediatr Neurol."},{"key":"R18-20230928","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/jssc.200700253","article-title":"Simultaneous determination of antiepileptic drugs and their two active metabolites by HPLC","volume":"31","author":"Budakova","year":"2008","journal-title":"J Sep Sci."},{"key":"R19-20230928","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/bmc.289","article-title":"High-performance liquid chromatographic determination of Levetiracetam in human plasma: comparison of different sample cleanup procedures","volume":"18","author":"Pucci","year":"2004","journal-title":"Biomed Chromatogr."},{"key":"R20-20230928","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/S0378-4347(00)83824-4","article-title":"Simple and sensitive method for monitoring clonazepam in human plasma and urine by high performance liquid chromatography","volume":"529","author":"Boukhabza","year":"1990","journal-title":"J Biomed Sci Appl."},{"key":"R21-20230928","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1365\/s10337-007-0310-y","article-title":"A capillary GC method using nitrogen phosphorus detection for determination of topiramate in patients with epilepsy","volume":"66","author":"Malakova","year":"2007","journal-title":"Chromatographia."},{"key":"R22-20230928","first-page":"416","article-title":"First experiences with therapeutic monitoring of antiepileptics [abstract]","volume":"34","author":"Brozmanova","year":"1985","journal-title":"Cesk Fysiol"},{"key":"R23-20230928","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/j.1365-2710.2004.00544.x","article-title":"Patterns of lamotrigine use in daily clinical practice during the first 5 years after introduction in The Netherlands","volume":"29","author":"Knoester","year":"2004","journal-title":"J Clin Pharm Ther."},{"key":"R24-20230928","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0920-1211(96)01007-8","article-title":"Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group","volume":"26","author":"Brodie","year":"1997","journal-title":"Epilepsy Res."},{"key":"R25-20230928","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.1528-1157.1999.tb00832.x","article-title":"The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction","volume":"40","author":"Pisani","year":"2009","journal-title":"Epilepsia."},{"key":"R26-20230928","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.2165\/00003495-200666140-00004","article-title":"Combination therapy in epilepsy","volume":"66","author":"Kwan","year":"2006","journal-title":"Drugs"},{"key":"R27-20230928","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0920-1211(02)00182-1","article-title":"Overtreatment in epilepsy: adverse consequences and mechanisms","volume":"52","author":"Perucca","year":"2002","journal-title":"Epilepsy Res."},{"key":"R28-20230928","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1111\/j.1528-1157.2000.tb00160.x","article-title":"Reduction of epileptiform activity in response to low-dose clonazepam in children with epilepsy: a randomized double-blind study","volume":"41","author":"Dahlin","year":"2000","journal-title":"Epilepsia."},{"issue":"suppl 8","key":"R29-20230928","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1528-1167.2009.02238.x","article-title":"Rational polytherapy","volume":"50","author":"French","year":"2009","journal-title":"Epilepsia"},{"key":"R30-20230928","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1212\/WNL.0b013e31823ed0dd","article-title":"Comparative efficacy of combination drug therapy in refractory epilepsy","volume":"78","author":"Poolos","year":"2012","journal-title":"Neurology"},{"key":"R31-20230928","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1046\/j.1472-8206.2001.00055.x","article-title":"The clinical pharmacology and therapeutic use of the new antiepileptic drugs","volume":"15","author":"Perucca","year":"2001","journal-title":"Fund Clin Pharmacol."},{"key":"R32-20230928","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1111\/j.1528-1167.2007.01201.x","article-title":"Lack of pharmacokinetic interaction of levetiracetam on carbamazepine, valproic acid, topiramate and lamotrigine in children with epilepsy","volume":"48","author":"Otoul","year":"2007","journal-title":"Epilepsia."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201710000-00010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:04:28Z","timestamp":1695863068000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201710000-00010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10]]},"references-count":30,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000433","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2017,10]]}}}