Commonly Used Newer Antiepileptic Drugs

  • MJ Eadie
  • FJE Vajda


Data are available in the literature for the clinical pharmacologies of three newer antiepileptic drugs which have achieved a moderate amount of use in pregnant women, viz. lamotrigine, topiramate and levetiracetam. There is more information available for the first of these drugs than for the other two. The clearance value for lamotrigine, which is almost fully biotransformed to glucuronides, is considerably increased during pregnancy, with the clearances of topiramate (eliminated by a mix of metabolism and renal excretion unchanged) and levetiracetam (eliminated mainly by renal excretion without prior metabolism) being less increased. Relatively little information is available concerning the dispositions of the three drugs in the neonate, though there are published data for maternal plasma to breast milk concentration ratios.


Antiepileptic Drug Maternal Plasma Antiepileptic Agent Lamotrigine Dose Lamotrigine Concentration 
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  1. Allegaent K, Lewi L, Naulars G, Lagae L (2006) Levetiracetam pharmacokinetics in neonates at birth. Epilepsia 47:1068–1069CrossRefGoogle Scholar
  2. Chen H, Yang K, Choi S, Fischer JH, Jeong H (2009) Up-regulation of UDP-glucuronosyltransferase (UGT) 1A4 by 17beta-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metab Dispos 37:1841–1847PubMedCentralCrossRefPubMedGoogle Scholar
  3. Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL (2013) Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry 170:1240–1247PubMedCentralCrossRefPubMedGoogle Scholar
  4. Davanzo R, Bo SD, Bua J, Copertino M, Zanelli E (2013) Antiepileptic drugs and breastfeeding. Ital J Pediatr 39:50PubMedCentralCrossRefPubMedGoogle Scholar
  5. de Haan GJ, Edelbroek P, Segers J, Engelsman M, Lindhout D, Devile-Notschaele M, Augustin P (2004) Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology 63:571–573CrossRefPubMedGoogle Scholar
  6. Fotopoulou C, Kretz R, Bauer S, Schefold JC, Schmitz B, Dudenhausen JW, Henrich W (2009) Prospectively assessed changes in lamotrigine-concentration in women with epilepsy during pregnancy, lactation and the neonatal period. Epilepsy Res 85:60–64CrossRefPubMedGoogle Scholar
  7. Franco V, Mazzucchelli I, Gatti G, Specchio LM, Papantonio A, Ozkaynakci AE, Perucca E (2008) Changes in lamotrigine pharmacokinetics during pregnancy and the puerperium. Ther Drug Monit 30:544–547PubMedGoogle Scholar
  8. Garnett WR (2000) Clinical pharmacology of topiramate: a review. Epilepsia 41(Suppl 1):S61–S65CrossRefPubMedGoogle Scholar
  9. Herzog AG, Blum AS, Farina EL et al (2009) Valproate and lamotrigine level variation with menstrual cycle phase and oral contraceptive use. Neurology 72:911–914CrossRefPubMedGoogle Scholar
  10. Johanessen SI, Helde G, Brodtkorb E (2005) Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia 46:775–777CrossRefGoogle Scholar
  11. Jovanovic M, Sokie D, Grabner I, Vovk T, Postran M, Vucicevic K, Miljkovic B (2013) Population pharmacokinetics of topiramate in adult patients with epilepsy using nonlinear mixed effects modelling. Eur J Pharm Sci 50:282–289CrossRefPubMedGoogle Scholar
  12. Kacirova I, Grundmann M, Brozmanova H (2010) Serum levels of lamotrigine during delivery in mothers and their infants. Epilepsy Res 91:161–165CrossRefPubMedGoogle Scholar
  13. Lopez-fraile IP, Cid AO, Juste AO, Modrego PJ (2009) Levetiracetam plasma level monitoring during pregnancy, delivery, and postpartum: clinical and outcome implications. Epilepsy Behav 15:372–375CrossRefPubMedGoogle Scholar
  14. Malone S, Addison R, Eadie MJ, Dickinson RG (2006) The monitoring of salivary lamotrigine concentrations. J Clin Neurosci 13:902–907CrossRefPubMedGoogle Scholar
  15. Myllynen PK, Pienimaki PK, Vahakangas KH (2003) Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo. Eur J Clin Pharmacol 58:677–682PubMedGoogle Scholar
  16. Newport DJ, Pennell PB, Calamaras MR et al (2008) Lamotrigine in breast milk and nursing infants: determination of exposure. Pediatrics 122:e223–231CrossRefPubMedGoogle Scholar
  17. Nordmo E, Aronsen L, Wasland K, Smabrekke L, Vorren S (2009) Severe apnea in an infant exposed to lamotrigine in breast milk. Ann Pharmacother 43:1893–1897CrossRefPubMedGoogle Scholar
  18. Ohman I, Vitols S, Tomson T (2000) Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation. Epilepsia 41:709–713CrossRefPubMedGoogle Scholar
  19. Ohman I, Vitols S, Luef G, Soderfeldt B, Tomson T (2002) Topiramate kinetics during delivery, lactation, and the neonate: preliminary observations. Epilepsia 43:1157–1160CrossRefPubMedGoogle Scholar
  20. Ohman I, Beck O, Vitols S, Tomson T (2008) Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy. Epilepsia 49:1075–1080CrossRefPubMedGoogle Scholar
  21. Ohman I, Sabers A, de Flon P, Luef G, Tomson T (2009) Pharmacokinetics of topiramate during pregnancy. Epilepsy Res 87:124–129CrossRefPubMedGoogle Scholar
  22. Patsalos PN, Berry DJ, Bourgeois BF et al (2008) Antiepileptic drugs – best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, I.L.A.E. Commission on Therapeutic Strategies. Epilepsia 49:1239–1276CrossRefPubMedGoogle Scholar
  23. Pennell PB, Newport DJ, Stowe ZN, Heimers SL, Montgomery JQ, Henry TR (2004) The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology 62:292–295CrossRefPubMedGoogle Scholar
  24. Pennell PB, Peng L, Newport DJ et al (2008) Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology 70:2130–2136PubMedCentralCrossRefPubMedGoogle Scholar
  25. Petrenaite V, Sabers A, Hansen-Schwartz J (2005) Individual changes in lamotrigine plasma concentrations during pregnancy. Epilepsy Res 65:185–188CrossRefPubMedGoogle Scholar
  26. Polepally AR, Pennell PB, Brundage RC et al (2014) Model-based lamotrigine clearance changes during pregnancy: clinical implication. Ann Clin Transl Neurol 1:99–106PubMedCentralCrossRefPubMedGoogle Scholar
  27. Rambeck B, Kurlemann G, Stodieck SR, May TW, Jurgens U (1997) Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child. Eur J Clin Pharmacol 51:481–484CrossRefPubMedGoogle Scholar
  28. Reimers A, Helge G, Brathen G, Brodkorb E (2011) Lamotrigine and its N2 glucuronide during pregnancy: the significance of renal clearance and oestradiol. Epilepsy Res 94:198–205CrossRefPubMedGoogle Scholar
  29. Reisinger TL, Newman M, Loring DW, Pennell PB, Meador KL (2013) Antiepileptic drug clearance and seizure frequency during pregnancy in women with epilepsy. Epilepsy Behav 29:13–18PubMedCentralCrossRefPubMedGoogle Scholar
  30. Rosenfeld WE, Doose DE, Walker SA, Nayak RA (1997) Effect of topiramate on the pharmacokinetics of oral contraceptives containing norethindrone and ethinyl oestradiol in patients with epilepsy. Epilepsia 38:317–323CrossRefPubMedGoogle Scholar
  31. Sabers A (2008) Pharmacokinetic interactions between contraceptives and antiepileptic drugs. Seizure 17:141–144CrossRefPubMedGoogle Scholar
  32. Shank RP, Gardocki JF, Streeter AJ, Maryanoff BE (2000) An overview of the preclinical aspects of topiramate: pharmacology, pharmacokinetics, and mechanism of action. Epilepsia 41(Suppl 1):S3–S9CrossRefPubMedGoogle Scholar
  33. Tomson T, Battino D (2007) Pharmacokinetics and therapeutic drug monitoring of newer antiepileptic drugs during pregnancy and the puerperium. Clin Pharmacokinet 46:209–219CrossRefPubMedGoogle Scholar
  34. Tomson T, Ohman I, Vitols S (1997) Lamotrigine in pregnancy and lactation: a case report. Epilepsia 38:1039–1041CrossRefPubMedGoogle Scholar
  35. Tomson T, Palm R, Kallen K et al (2007) Pharmacokinetics of levetiracetam during pregnancy, delivery, in the neonatal period, and lactation. Epilepsia 48:1111–1116CrossRefPubMedGoogle Scholar
  36. Tran TA (2002) Lamotrigine clearance during pregnancy. Neurology 59:251–255CrossRefPubMedGoogle Scholar
  37. Wegner I, Edelbroek PM, Bulk S, Lindhout D (2009) Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraception. Neurology 73:1388–1393CrossRefPubMedGoogle Scholar
  38. Westin AA, Reimers A, Heide G, Nakken KO, Brodtkorb E (2008) Serum concentration/dose ratio of levetiracetam before, during and after pregnancy. Seizure 17:192–198CrossRefPubMedGoogle Scholar
  39. Westin AA, Nakken KO, Johannessen SI, Reimers A, Lillestolen KM, Brodkorb E (2009) Serum concentration/dose ratio of topiramate during pregnancy. Epilepsia 50:480–485CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • MJ Eadie
    • 1
  • FJE Vajda
    • 2
  1. 1.Clinical Neurology and NeuropharmacologyUniversity of Queensland, and Honorary Consultant Neurologist, Royal Brisbane and Women’s HospitalBrisbaneAustralia
  2. 2.Department of Medicine and Neurology Director of the Australian Epilepsy and Pregnancy RegisterUniversity of Melbourne and Royal Melbourne HospitalMelbourneAustralia

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