Is Therapeutic Drug Monitoring of Lacosamide Needed in Patients with Seizures and Epilepsy?


Lacosamide is an antiepileptic drug (AED) that has linear pharmacokinetics, predictable blood concentrations, and few drug interactions, setting it apart from other AEDs that require vigorous therapeutic drug monitoring (TDM) such as phenytoin and carbamazepine. However, there have been reports of altered lacosamide pharmacokinetics in some populations. The purpose of this review is to determine whether lacosamide pharmacokinetics are altered in certain patient populations, suggesting the need for TDM. A literature search of Medline, Scopus, Embase, and Cochrane trials was conducted on January 3, 2019 (and then updated on September 2, 2019) to search for articles relevant to the TDM or pharmacokinetics of lacosamide. A total of 56 relevant articles were found and included in this review. Dose of lacosamide is linearly correlated with plasma concentrations and efficacy. However, currently there is no well-established reference range. Overall, the recommended reference ranges varied from 2.2 to 20 mg/L. Lacosamide has very few clinically relevant drug–drug interactions; however, there seems to be a significant drug interaction between lacosamide and enzyme-inducer AEDs. Based on available literature, it appears that lacosamide pharmacokinetics may be altered in severe renal dysfunction, in patients on dialysis and with extremes of age. More evidence is currently needed on lacosamide pharmacokinetics in pregnancy and critical illness. While it is not practical to utilize TDM for all patients, TDM may be useful in patients taking enzyme-inducer AEDs, in patients with decreased renal function or on dialysis, and older adults.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Fig. 1


  1. 1.

    UCB Pharma. Vimpat Product Monograph (Canada). 2018.

  2. 2.

    UCB Pharma. Vimpat Product Monograph (EMA). 2018.

  3. 3.

    Errington AC, Stöhr T, Heers C, Lees G. The investigational anticonvulsant lacosamide selectively enhances slow inactivation of voltage-gated sodium channels. Mol Pharmacol. 2008;73(1):157 LP-169.

  4. 4.

    Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, et al. Adjunctive lacosamide for partial-onset seizures: efficacy and safety results from a randomized controlled trial. Epilepsia. 2009;50(3 CC-Epilepsy):443–53.

  5. 5.

    Kropeit D, Johnson M, Cawello W, et al. Lacosamide cardiac safety: a thorough QT/QTc trial in healthy volunteers. Acta Neurol Scand. 2015;132(5):346–54.

  6. 6.

    Cawello W, Boekens H, Bonn R. Absorption, disposition, metabolic fate and elimination of the anti-epileptic drug lacosamide in humans: mass balance following intravenous and oral administration. Eur J Drug Metab Pharmacokinet. 2012;37(4):241–8.

  7. 7.

    Cawello W, Fuhr U, Hering U, Maatouk H, Halabi A. Impact of impaired renal function on the pharmacokinetics of the antiepileptic drug lacosamide. Clin Pharmacokinet. 2013;52(10):897–906.

  8. 8.

    Patsalos PN, Spencer EP, Berry DJ, et al. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40(5):526–48.

  9. 9.

    Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduction—GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.

  10. 10.

    Chung S, Ben-Menachem E, Sperling MR, et al. Examining the clinical utility of lacosamide: pooled analyses of three phase IIIII clinical trials. CNS Drugs. 2010;24(12):1041–54.

  11. 11.

    Ben-Menachem E, Biton V, Jatuzis D, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007;48(7):1308–17.

  12. 12.

    Lindauer A, Laveille C, Stockis A. Time-to-seizure modeling of lacosamide used in monotherapy in patients with newly diagnosed epilepsy. Clin Pharmacokinet. 2017;56(11):1403–13.

  13. 13.

    Morris G, Burgos J, Van Kampen A, Hanson M, Dagman J. Intravenous intiation of lacosamide for status epilepticus and following video EEG monitoring. Epilepsy Curr. 2015; 15(1):157.

  14. 14.

    Payto D, Foldvary-Schaefer N, So N, Bruton M, Wang S. Establishment of expected ranges for the random serum concentration of lacosamide and desmethyl lacosamide. Clin Chem. 2014;60(10 Suppl. 1):S247–8.

  15. 15.

    Perrenoud M, Andre P, Alvarez V, et al. Intravenous lacosamide in status epilepticus: correlation between loading dose, serum levels, and clinical response. Epilepsy Res. 2017;135:38–42.

  16. 16.

    Svendsen T, Brodtkorb E, Baftiu A, et al. Therapeutic drug monitoring of lacosamide in norway: focus on pharmacokinetic variability, efficacy and tolerability. Neurochem Res. 2017;42(7):2077–83.

  17. 17.

    Hillenbrand B, Wisniewski I, Jürges U, Steinhoff BJ. Add-on lacosamide: a retrospective study on the relationship between serum concentration, dosage, and adverse events. Epilepsy Behav. 2011;22(3):548–51.

  18. 18.

    Sattler A, Schaefer M, May TW, et al. Fluctuation of lacosamide serum concentrations during the day and occurrence of adverse drug reactions–first clinical experience. Epilepsy Res. 2011;95(3):207–12.

  19. 19.

    Brandt C, Bien CG, Helmer R, May TW. Assessment of the correlations of lacosamide concentrations in saliva and serum in patients with epilepsy. Epilepsia. 2018;59(4):e34–9.

  20. 20.

    Greenaway C, Ratnaraj N, Sander JW, Patsalos PN. Saliva and serum lacosamide concentrations in patients with epilepsy. Epilepsia. 2011;52(2):258–63.

  21. 21.

    Cawello W, Bokens H, Nickel B, et al. Tolerability, pharmacokinetics, and bioequivalence of the tablet and syrup formulations of lacosamide in plasma, saliva, and urine: saliva as a surrogate of pharmacokinetics in the central compartment. Epilepsia. 2013;54(1):81–8.

  22. 22.

    May TW, Brandt C, Helmer R, et al. Comparison of lacosamide concentrations in cerebrospinal fluid and serum in patients with epilepsy. Epilepsia. 2015;56(7):1134–40.

  23. 23.

    Michelhaugh SK, Basha M, Rhoney DH, Shah AK, Mittal S. Acute or chronic use of lacosamide does not alter its distribution between serum and cerebrospinal fluid. Epilepsia. 2015;56(11):1732–7.

  24. 24.

    Cawello W, Bonn R. No pharmacokinetic interaction between lacosamide and valproic acid in healthy volunteers. J Clin Pharmacol. 2012;52(11):1739–48.

  25. 25.

    Cawello W, Nickel B, Eggert-Formella A. No pharmacokinetic interaction between lacosamide and carbamazepine in healthy volunteers. J Clin Pharmacol. 2010;50(4):459–71.

  26. 26.

    Cawello W. Exposure to lacosamide in blood plasma during adjunctive therapy and monotherapy: pharmacokinetic analysis of data from a conversion to lacosamide monotherapy study. Epilepsia. 2015;56(Suppl. 1):53.

  27. 27.

    Chung S, Sperling MR, Biton V, et al. Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial. Epilepsia. 2010;51(6):958–67.

  28. 28.

    May TW, Helmer R, Bien CG, et al. Influence of dose and antiepileptic comedication on lacosamide serum concentrations in patients with epilepsy of different ages. Ther Drug Monit. 2018;40(5):620–7.

  29. 29.

    Contin M, Albani F, Riva R, et al. Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013;35(6):849–52.

  30. 30.

    Markoula S, Teotonio R, Ratnaraj N, et al. Lacosamide serum concentrations in adult patients with epilepsy: the influence of gender, age, dose, and concomitant antiepileptic drugs. Ther Drug Monit. 2014;36(4):494–8.

  31. 31.

    Ota M, Demura A, Hashi S, Kinoshita M. Pharmacokinetic drug–drug interaction between lacosamide and other antiepileptic drugs in Japanese adult patients with epilepsy. Epilepsia. 2018;59(Suppl. 3):S272.

  32. 32.

    Novy J, Patsalos PN, Sander JW, Sisodiya SM. Lacosamide neurotoxicity associated with concomitant use of sodium channel-blocking antiepileptic drugs: a pharmacodynamic interaction? Epilepsy Behav. 2011;20(1):20–3.

  33. 33.

    Cawello W, Rosenkranz B, Schmid B, Wierich W. Pharmacodynamic and pharmacokinetic evaluation of coadministration of lacosamide and an oral contraceptive (levonorgestrel plus ethinylestradiol) in healthy female volunteers. Epilepsia. 2013;54(3):530–6.

  34. 34.

    Cawello W, Mueller-Voessing C, Fichtner A, et al. Pharmacokinetics of lacosamide and omeprazole coadministration in healthy volunteers: results from a phase I, randomized, crossover trial. Clin Drug Investig. 2014;34(5):317–25.

  35. 35.

    Cawello W, Mueller-Voessing C, Andreas J-O. Effect of lacosamide on the steady-state pharmacokinetics of digoxin: results from a phase I, multiple-dose, double-blind, randomised, placebo-controlled, crossover trial. Clin Drug Investig. 2014;34(5):327–34.

  36. 36.

    Biton V, Rosenfeld WE, Whitesides J, et al. Intravenous lacosamide as replacement for oral lacosamide in patients with partial-onset seizures. Epilepsia. 2008;49(3):418–24.

  37. 37.

    Cawello W, Bonn R, Boekens H. Bioequivalence of intravenous and oral formulations of the antiepileptic drug lacosamide. Pharmacology. 2012;90(1–2):40–6.

  38. 38.

    Fountain NB, Krauss G, Isojarvi J, et al. Safety and tolerability of adjunctive lacosamide intravenous loading dose in lacosamide-naive patients with partial-onset seizures. Epilepsia. 2013;54(1):58–65.

  39. 39.

    Krauss G, Ben-Menachem E, Mameniskiene R, et al. Intravenous lacosamide as short-term replacement for oral lacosamide in partial-onset seizures. Epilepsia. 2010;51(6):951–7.

  40. 40.

    Schaefer C, Cawello W, Andreas JO. Immediate steady state concentrations in plasma after oral or intravenous lacosamide loading dose. Epilepsy Curr. 2015;15(Suppl. 1):524–5.

  41. 41.

    Rémi C, Zwanzig V. Subcutaneous use of lacosamide. J Pain Symptom Manag. 2016;51(2):e2–4.

  42. 42.

    Ward RM, Varner MW. Principles of pharmacokinetics in the pregnant woman and fetus. Clin Perinatol. 2019;46(2):383–98.

  43. 43.

    Ylikotila P, Ketola RA, Timonen S, et al. Early pregnancy cerebral venous thrombosis and status epilepticus treated with levetiracetam and lacosamide throughout pregnancy. Reprod Toxicol. 2015;57:204–6.

  44. 44.

    Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118–26.

  45. 45.

    Franquiz MJ, Kalaria SN, Armahizer MJ, et al. Lacosamide pharmacokinetics in a critically ill patient receiving continuous venovenous hemofiltration. Pharmacotherapy. 2018;38(2):e17–21.

  46. 46.

    Wieruszewski PM, Lopez-Ruiz A, Albright RC et al. Lacosamide pharmacokinetics in a critically ill patient during continuous renal replacement therapy. J Pharm Pract. 2018:897190018803765.

  47. 47.

    Klotz U. The elderly—a challenge for appropriate drug treatment. Eur J Clin Pharmacol. 2008;64(3):225–6.

  48. 48.

    Cawello W, Schafer C. A system of equations to approximate the pharmacokinetic parameters of lacosamide at steady state from one plasma sample. Epilepsy Res. 2014;108(6):1068–75.

  49. 49.

    Schaefer C, Cawello W, Waitzinger J, Elshoff J-P. Effect of age and sex on lacosamide pharmacokinetics in healthy adult subjects and adults with focal epilepsy. Clin Drug Investig. 2015;35(4):255–65.

  50. 50.

    Ramsay RE, Sabharwal V, Khan F, et al. Safety & pK of IV loading dose of lacosamide in the ICU. Epilepsy Behav. 2015;49:340–2.

  51. 51.

    Mahulikar A, Yarranguntla K, Shah A, Seraji-Bozorgzad N, Basha M. Racial influence on antiepileptic drug levels. Neurol. 2018;90(15):P5.259.

  52. 52.

    Nahata MC, Taketomo C. Pediatrics. In: DiPiro JT, Talbert RL, Yee GC, editors. Pharmacotherapy: A Pathophysiologic Approach, 10th edition. New York: McGraw-Hill Education; 2017.

  53. 53.

    Burns ML, Nikanorova M, Baftiu A et al. Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway. Ther Drug Monit. 2019;41(3):340–347.

  54. 54.

    Kronenfeld N, Kohn E, Lezinger M, et al. Lacosamide monitoring in the serum of children with refractory epilepsy. Arch Dis Child. 2019.

  55. 55.

    Martin P, Stockis A, Jolling K. Population pharmacokinetic modelling and simulation to support dose recommendations for lacosamide in children. Epilepsia. 2018;59(Suppl. 3):S78.

  56. 56.

    Winkler J, Schoemaker R, Stockis A. Population pharmacokinetics of adjunctive lacosamide in pediatric patients with epilepsy. J Clin Pharmacol. 2018.

  57. 57.

    Winkler J, Schoemaker R, Stockis A. Modeling and simulation for the evaluation of dose adaptation rules of intravenous lacosamide in children. Epilepsy Res. 2019;149:13–6.

  58. 58.

    Bautista RE, Graham C, Mukardamwala S. Do lacosamide serum levels differ in African American and caucasian groups? Epilepsy Curr. 2012;12(1).

  59. 59.

    Hong Z, Inoue Y, Liao W, et al. Efficacy and safety of adjunctive lacosamide for the treatment of partial-onset seizures in Chinese and Japanese adults: a randomized, double-blind, placebo-controlled study. Epilepsy Res. 2016;127:267–75.

  60. 60.

    Yamamoto Y, Terada K, Takahashi Y, et al. Therapeutic drug monitoring for lacosamide in Japanese patients with epilepsy. Eur J Clin Pharmacol. 2019;75(Suppl. 1):S40.

  61. 61.

    Kim SE, Gu N, Kim B-H, et al. Pharmacokinetics of lacosamide in healthy Korean male volunteers. Pharmacology. 2012;89(3–4):172–8.

  62. 62.

    Mahmoud SH, Yearwood C. Critical Care Assessment. In: Mahmoud SH (ed.) Patient assessment in clinical pharmacy: a comprehensive guide. Springer International Publishing. 2019;353–373.

  63. 63.

    Mahmoud HS, Shen C. Augmented renal clearance in critical illness: an important consideration in drug dosing. Pharmaceutics. 2017.

  64. 64.

    Cherry S, Judd L, Carlos J, et al. Safety and efficacy of lacosamide in the intensive care unit. Neurocrit Care. 2012;16:294–8.

  65. 65.

    Luk ME, Tatum WO, Patel AV, et al. The safety of lacosamide for treatment of seizures and seizure prophylaxis in adult hospitalized patients. Neurohospitalist. 2012;2(3):77–81.

  66. 66.

    Landmark CJ, Svendsen T, Brodtkorb E, et al. Comparison of lacosamide treatment in patients with and without intellectual disability. Epilepsia. 2018;59(Suppl. 3):S173–4.

  67. 67.

    Berei TJ, Lillyblad MP, Almquist AK. Lacosamide-induced recurrent ventricular tachycardia in the acute care setting. J Pharm Pract. 2018;31(2):222–6.

  68. 68.

    Deslandes G, Bouquié R, Lorber J, et al. Status epilepticus following self-poisoning of lacosamide and lamotrigine: a case report with follow-up of drug serum concentrations. Toxicol Anal Clin. 2015;27(2):88–90.

  69. 69.

    Kiernan E, et al. Hemodialysis: the final frontier for acute lacosamide toxicity? J Med Toxicol. 2019;15(2):63.

  70. 70.

    Payto D, Foldvary-Schaefer N, So N, et al. A sensitive and rapid method for quantification of lacosamide and desmethyl lacosamide by LC-MS/MS. Bioanalysis. 2014;6(23):3161–8.

  71. 71.

    D’urso A, Ricotta T, de Grazia U, et al. Evaluation of a novel immunoassay for lacosamide therapeutic drug monitoring: comparison with a liquid chromatography-mass spectrometry assay. Ther Drug Monit. 2017;39(6):663–8.

  72. 72.

    Nikolaou P, Papoutsis I, Spiliopoulou C, et al. A fully validated method for the determination of lacosamide in human plasma using gas chromatography with mass spectrometry: application for therapeutic drug monitoring. J Sep Sci. 2015;38(2):260–6.

  73. 73.

    Korman E, Bjergum M, Danso D, et al. High-throughput validatedmethod for the quantification of lacosamide in serum using ultra fast SPE-MS/MS. Ther Drug Monit. 2013;35(5):675.

Download references


Janice Kung, Librarian at John W. Scott Library, for assisting with the keywords selection and search strategy.

Author information

SHM had the idea of the article. LS performed the literature search and data abstraction and summarization. Both authors confirmed data collected and search and wrote the manuscript.

Correspondence to Sherif Hanafy Mahmoud.

Ethics declarations

Conflict of interest

Authors have no conflicts of interest to declare.


There is no funding associated with this work.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Schultz, L., Mahmoud, S.H. Is Therapeutic Drug Monitoring of Lacosamide Needed in Patients with Seizures and Epilepsy?. Eur J Drug Metab Pharmacokinet (2020).

Download citation