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Valproic Acid

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Antiseizure Medication Interactions

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Abstract

The pharmacokinetic characteristics of valproic acid are described and the interaction effects of concomitant antiseizure medications on valproic acid in terms of its pharmacokinetics and pharmacodynamics are highlighted.

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References

  1. Moseley BD, Otoul C, Staelens L, Stockis A. Pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with focal seizures: pooled analysis of data from randomized clinical trials. Epilepsy Res. 2019;158:106218.

    Article  CAS  Google Scholar 

  2. Ben-Menachem E, Gunning B, Cabrera CMA, Van Landingham K, Crockett J, Critchley D, Wray L, Tayo B, Morrison G, Toledo M. A phase II randomized trial to explore the potential for pharmacokinetic drug-drug interactions with stiripentol or valproate when combined with cannabidiol in patients with epilepsy. CNS Drugs. 2020;34:661–72.

    Article  CAS  Google Scholar 

  3. Patsalos PN, Szaflarski JP, Gidal B, Van Landingham K, Critchley D, Morrison G. Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs. Epilepsia. 2020;61:1854–68.

    Article  CAS  Google Scholar 

  4. Panesar SK, Orr JM, Farrell K, Burton RW, Kassahun K, Abbott FS. The effect of carbamazepine on valproic acid disposition. Br J Clin Pharmacol. 1989;27:323–8.

    Article  CAS  Google Scholar 

  5. Levy R, Rettenmeier AW, Anderson GD, Wilensky AJ, Friel PN, Bailie TA, Acheampong A, Tor J, Guyot M, Loiseau P. Effects of polytherapy with phenytoin, carbamazepine, and stiripentol on formation of 4-ene-valproate, a hepatotoxic metabolite of valproic acid. Clin Pharmacol Ther. 1990;48:225–35.

    Article  CAS  Google Scholar 

  6. Brodie MJ, Mumford JP. Double-blind substitution of vigabatrin and valproate in carbamazepine-resistant partial epilepsy. 012 study group. Epilepsy Res. 1999;34:199–205.

    Article  CAS  Google Scholar 

  7. Bialer M, Johannessen SI, Koepp MJ, Levy RH, Perucca E, Perucca P, Tomson T, White HS. Progress report on new antiepiletis drugs: a summary of the fifteenth Eilat conference on new antiepileptic drugs and devices (EILAT XV). II. Drugs in more advanced clinical development. Epilepsia. 2020;61:2365–85.

    Article  CAS  Google Scholar 

  8. Theis JGW, Koren G, Daneman R, Sherwin AL, Menzano E, Cortez M, Hwang P. Interactions of clobazam with conventional antiepileptics in children. J Child Neurol. 1997;12:208–13.

    Article  CAS  Google Scholar 

  9. Wang L, Wang XD. Pharmacokinetic and pharmacodynamic effects of clonazepam in children with epilepsy treated with valproate: a preliminary study. Ther Drug Monit. 2002;24:632–6.

    Article  Google Scholar 

  10. Elger C, Halasz P, Maia J, Almeidas L, Soares-da-Silva P, BIA-2093-301 Investigators Study Group. Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial seizures: a randomized, double-blind, placebo-controlled, parallel-group phase III study. Epilepsia. 2009;50:454–63.

    Article  CAS  Google Scholar 

  11. Falcao A, Fuseau E, Nunes T, Almeida L, Soares-da-Silva P. Pharmacokinetics, drug interactions and exposure-response relationships of eslicarbazepine acetate in adult patients with partial-onset seizures: population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis. CNS Drugs. 2012;26:79–91.

    Article  CAS  Google Scholar 

  12. Salke-Kellermann RA, May T, Boenigk HE. Influence of ethosuximide on valproic acid serum concentrations. Epilepsy Res. 1997;26:345–9.

    Article  CAS  Google Scholar 

  13. Rowan AJ, Meijer JW, de Beer-Pawlikowski N, van der Geest P, Meinardi H. Valproate-ethosuximide combination therapy for refractory seizures. Arch Neurol. 1983;40:797–802.

    Article  CAS  Google Scholar 

  14. Wagner ML, Graves NM, Leppik IE, Remmel RP, Shmaker RC, Ward D, Perhach JL. The effect of felbamate on valproic acid disposition. Clin Pharmacol Ther. 1994;56:494–502.

    Article  CAS  Google Scholar 

  15. Boyd B, Smith S, Gammaitoni A, Galer BS, Farfel GM. A phase 1, randomized, open-label, single dose, 3 period crossover study to evaluate the drug-drug interaction between ZX008 (fenfluramine HCl oral solution) and a regimen of stiripentol, clobazam, and valproate in healthy subjects. Int J Clin Pharmaol Therapeut. 2019;57:11–9.

    Article  Google Scholar 

  16. Radulovic LL, Wilder BJ, Leppik IE, Bockbrader HN, Chang T, Posvar EL, Sedman AJ, Uthman BM, Erdman GR. Lack of interaction of gabapentin with carbamazepine and valproate. Epilepsia. 1994;35:155–61.

    Article  CAS  Google Scholar 

  17. Toutopoulou M, Weshke B, Kaindl AM. Lacsamide lowers valproate and levetiracetam levels. Neuropediatrics. 2017;48:188–9.

    Article  Google Scholar 

  18. Jones GL, Popli GS, Silvia MT. Lacosamide-induced valproic acid toxicity. Pediatr Neurol. 2013;48:308–10.

    Article  Google Scholar 

  19. Anderson GD, Yau MK, Gidal BE, Harris SJ, Levy RH, Lai AA, Wolf KB, Wargin WA, Dren AT. Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharmacol Ther. 1996;60:145–56.

    Article  CAS  Google Scholar 

  20. Kanner AM. When thinking of lamotrigine and valproic acid, think “pharmacokinetically”. Epilepsy Curr. 2004;4:206–7.

    Article  Google Scholar 

  21. Brodie MJ, Yuen AW. Lamotrigine substitution study: evidence for synergism with sodium valproate? 105 Study Group. Epilepsy Res. 1997;26:423–33.

    Article  CAS  Google Scholar 

  22. Pisani F, Oteri G, Russo MF, Di Perri R, Perucca E, Richens A. The efficacy of valproate-lamotrigine comedication in refractory complex partial seizures: evidence for a pharmacodynamic interaction. Epilepsia. 1999;40:1141–6.

    Article  CAS  Google Scholar 

  23. Reutens DC, Duncan JS, Patsalos PN. Disabling tremor after lamotrigine with sodium valproate. Lancet. 1993;342:185–6.

    Article  CAS  Google Scholar 

  24. Coupez R, Nicolas JM, Browne TR. Levetiracetam, a new antiepileptic agent: lack of in vitro and in vivo pharmacokinetic interaction with valproic acid. Epilepsia. 2003;44:171–8.

    Article  CAS  Google Scholar 

  25. Besag FM, Berry DJ, Vasey M. Methsuximide reduces valproic acid serum levels. Ther Drug Monit. 2001;23:694–7.

    Article  CAS  Google Scholar 

  26. McKee PJW, Blacklaw J, Forrest G, Gillham RA, Walker SM, Connelly D, Brodie MJ. A double-blind, placebo-controlled interaction study between oxcarbazepine and carbamazepine, sodium valproate and phenytoin in epileptic patients. Br J Clin Pharmacol. 1994;37:27.32.

    Article  Google Scholar 

  27. Majid O, Laurenza A, Ferry J, Hussein Z. Impact of perampanel on pharmacokinetics of concomitant antiepileptics in patients with partial-onset seizures: pooled analysis of clinical trials. Br J Clin Pharmacol. 2016;82:422–30.

    Article  CAS  Google Scholar 

  28. Gidal BE, Ferry J, Laurenza A, Ueno T. Potential protein-binding displacement interactions with perampanel: an in vitro analysis. Epilepsy Res. 2019;149:102–6.

    Article  CAS  Google Scholar 

  29. Sackellares JC, Sato S, Dreifuss FE, Penry JK. Reduction of steady-state valproate levels by other antiepileptic drugs. Epilepsia. 1981;22:437–41.

    Article  CAS  Google Scholar 

  30. Summary of product characteristics: Piracetam (Nootropil). UCB Pharma Ltd. Last update 9th Feb 2017.

    Google Scholar 

  31. Brodie MJ, Wilson EA, Wesche DL, Alvey CW, Randinitis EJ, Posvar EL, Hounslow NJ, Bron NJ, Gibson GL, Bockbrader HN. Pregabalin drug interaction studies: lack of effect on the pharmacokinetics of carbamazepine, phenytoin, lamotrigine, and valproate in patients with partial epilepsy. Epilepsia. 2005;46:1407–13.

    Article  CAS  Google Scholar 

  32. Perucca E, Cloyd J, Critchley D, Fuseau E. Rufinamide: clinical pharmacokinetics and concentration-response relationships in patients with epilepsy. Epilepsia. 2008;49:1123–41.

    Article  CAS  Google Scholar 

  33. Gustavson LE, Sommerville KW, Boellner SW, Witt GF, Guenther HJ, Granneman GR. Lack of a clinically significant pharmacokinetic interaction between tiagabine and valproate. Am J Ther. 1998;5:73–9.

    Article  CAS  Google Scholar 

  34. Rosenfeld WE, Liao S, Kramer LD, Anderson G, Palmer M, Levy RH, Nayak RN. Comparison of the steady-state pharmacokinetics of topiramate and valproate in patients with epilepsy during monotherapy and concomitant therapy. Epilepsia. 1997;38:324–33.

    Article  CAS  Google Scholar 

  35. Noh Y, Kim DW, Chu K, Lee ST, Jung KH, Moon HJ, Lee SK. Topiramate increases the risk of valproic acid-induced encephalopathy. Epilepsia. 2013;54:e1–4.

    Article  CAS  Google Scholar 

  36. Armijo JA, Arteaga R, Valdizan EM, Herranz JL. Coadministration of vigabatrin and valproate in children with refractory epilepsy. Clin Neuropharmacol. 1992;15:459–69.

    Article  CAS  Google Scholar 

  37. Ragueneau-Majlessi I, Levy RH, Brodie MJ, Smith D, Shah J, Grundy JS. Lack of pharmacokinetic interactions between steady-state zonisamide and valproic acid in patients with epilepsy. Clin Pharmacokinet. 2005;44:517–23.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK

    Philip N. Patsalos

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  1. Philip N. Patsalos
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Correspondence to Philip N. Patsalos .

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Patsalos, P.N. (2022). Valproic Acid. In: Antiseizure Medication Interactions. Springer, Cham. https://doi.org/10.1007/978-3-030-82790-8_31

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  • DOI: https://doi.org/10.1007/978-3-030-82790-8_31

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-82789-2

  • Online ISBN: 978-3-030-82790-8

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