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Adverse effects and interactions with other drugs

  • Chapter
Valproate

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

The ascertainment of valproate-induced adverse effects is fraught with a number of specific problems. Valproate was introduced in Europe in the early 1960s when few clinical trials were required, and those performed have simply used incidence reporting following passive inquiry. The prevalence and incidence of adverse effects has not been reported at different points during these early trials and, apart from withdrawal from the trial, no quantification of the severity and the impact of adverse effects was possible. Furthermore, the pharmaceutical formulation of valproate was changed several times over the years. More recently, enteric coated and slow release preparations were introduced which incidentally reduced the number of adverse reactions [1]. In addition, the indications which were initially limited to idiopathic generalized seizures could be widened to include not only virtually all types of epileptic seizures but also into other therapeutic areas such as migraine and acute mania. Despite the wide and well accepted use of valproate, it took decades to discover altogether rare but serious adverse effects. These include acute liver failure [2] and an increased rate of congenital malformations, especially neural tube defects in the offspring of women who had taken valproate during pregnancy [3]. Even after being on the market for so many years, new adverse effects continue to be discovered.

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References

  1. Wilder BJ et al (1983) Gastrointestinal tolerance of divalproex sodium. Neurology 33: 808–811

    Article  PubMed  CAS  Google Scholar 

  2. Bryant A E, Dreifuss FE (1996) Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology 46: 465–469

    Article  PubMed  Google Scholar 

  3. Lindhout D, Schmidt D (1986) In-utero exposure of valproate and neural tube defects. Lancet I: 1392–1393 (letter)

    Google Scholar 

  4. Isojärvi JIT, Laatikainen TJ, Knip M, Pakarinen AJ, Juntunen KT, Myllylae VV (1996) Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 39: 579–584

    Article  PubMed  Google Scholar 

  5. Murialdo G, Galimberti CA, Magri G, et al (1997) Menstrual cycle and ovary alterations in women with epilepsy on antiepileptic therapy. Endocrinol Invest 20(9): 519–526

    Google Scholar 

  6. Schmidt D (1982) Adverse Effects of Antiepileptic Drugs. Raven Press, New York

    Google Scholar 

  7. Schmidt D (1992) Anticonvulsants. In: MNG Dukes (ed): Meylers side-effects of drugs,12th Ed. Elsevier Science Publishers BV, New York, 122–143

    Google Scholar 

  8. Schmidt D (1984) Adverse effects of valproate. Epilepsia 25 (Suppl. 1): S 44—S 49

    Article  Google Scholar 

  9. Davis R, Peters DH, McTavish D (1994) Valproic Acid. A reappraisal of its pharmacological properties and clinical efficacy in epilepsy. Drugs 47: 332–372

    Article  PubMed  CAS  Google Scholar 

  10. Dreifuss FE (1995) Valproic acid. Toxicity. In: RH Levy, RH Mattson, BS Meldrum (eds): Antiepileptic drugs. Raven Press, New York, 641–648

    Google Scholar 

  11. Loiseau P (1996) Tolerability of newer and older antiepileptic drugs: a comparative review. CNS Drugs 6: 148–166

    Article  CAS  Google Scholar 

  12. Stephens JR, Levy RH (1994) Effects of valproate and citrulline on ammonium-induced encephalopathy. Epilepsia 35: 164–171

    Article  PubMed  CAS  Google Scholar 

  13. Armon C, Shin C, Miller P, Carwile S, Brown E, Edinger JD, Paul RG (1996) Reversible Parkinsonism and cognitive impairment with chronic valproate use. Neurology 47: 626–635

    Article  PubMed  CAS  Google Scholar 

  14. Hurst SI, Hargreaves JA, Howald WN, Racha JK, Mather GG, Labroo R, Carlson SP, Levy RH (1997) Enzymatic mechanism for the phenobarbital-valproate interaction. Epilepsia 38; Suppl 8: 111–112

    Google Scholar 

  15. Dinesen H, Gram L, Andersen T, Dam M (1984) Weight gain during treatment with valproate. Acta Neurol Scand 70: 65–69

    Article  PubMed  CAS  Google Scholar 

  16. Gidal BE, Anderson GD, Spencer WD, et al (1994) Valproic acid (VPA) associated weight gain in monotherapy patients with epilepsy. Epilepsia 35: S142

    Google Scholar 

  17. Mattson RH, Cramer JA, Collins JF, The Department of Veterans Affairs Epilepsy Cooperative Study No. 264 Group (1992) A comparison of valproate with carbamazepine for the treatment of complex partial seizures and secondarily generalized tonic-clonic seizures in adults. N Engl J Med 327: 765–771

    Article  CAS  Google Scholar 

  18. Verity CM, Hosking G, Easter DJ, The Peadiatric EPITEG Collaborative Group (1995) A multicentre comparative trial of sodium valproate and carbamazepine in pediatric epilepsy. Dev Med Child Neurol 37: 97–108

    Article  PubMed  CAS  Google Scholar 

  19. Davidson DLW (1989) The adult EPITEG trial: a comparative multicentre clinical trial of sodium valproate and carbamzepine in adult onset epilepsy. Part 2: Adverse effects. In: D Chadwick (ed) Proceedings of the Fourth International Symposium on Sodium Valproate and Epilepsy, International Congress and Symposium Series No. 152, Royal Society of Medicine Services, London, 114–121

    Google Scholar 

  20. Weber M, Loiseau P, Boon P, Cunha L, Herranz JL, Siebenga E, Stodieck S, Broglin D, Labadie F, Robin JL, Djouadi (1993) Comparative multicentre study of the efficacy and tolerability of controlled release form of sodium valproate (Depakine Chrono R) and carbamazepine (Tegretol LP R) in partial Epilepsy. 20th International Epilepsy Congress, Oslo (Norway) Sanofi Recherche

    Google Scholar 

  21. Christe W, Krämer G, Vigonius U, Pohlmann H, Steinhoff B, Brodie M, Moore A (1997) A double-blind controlled clinical trial: oxcarbazepine versus sodium valproate in adults with newly diagnosed epilepsy. Epilepsy Res 26: 451–460

    Article  PubMed  CAS  Google Scholar 

  22. COSTART — coding symbols for thesaurus of adverse reaction terms. 3rd ed. Rockville MD (1989) Food and Drug Administration, Center for Drug Evaluation and Research

    Google Scholar 

  23. Willmore LJ, Shu V, Wallin B, the M88–194 Study Group (1996) Efficacy and safety of add-on divalproex sodium in the treatment of complex partial seizures. Neurology 46: 49–53

    Article  PubMed  CAS  Google Scholar 

  24. Giroud M, Gras D, Escousse A, Dumas R, Venaud G (1993) Use of intractable valproic acid in status epilepticus. A pilot study. Drug Invest 5: 154–159

    Article  Google Scholar 

  25. Devinsky O, Leppik I, Willmore LJ, Pellock JM, Dean C, Gates J, Ramsay RE, Intravenous Valproate Study Team (1995) Safety of intravenous valproate. Ann Neurol 38: 670–674

    Article  PubMed  CAS  Google Scholar 

  26. Ramsay RE, Uthman B, Leppik IE, Pellock JM, Wilder BJ, Morris D, Cloyd JC (1997) The tolerability and safety of valproate sodium injection given as an intravenous infusion. J Epilepsy 10: 187–193

    Article  Google Scholar 

  27. Physicians’ Desk Reference (1997) 51th Edition, Medical Economics Company, Montvale, NJ

    Google Scholar 

  28. Callaghan N, Majeed T, O’Connell A, Oliveira DBG (1994) A comparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients. Acta Neurol Scand 89: 237–241

    Article  PubMed  CAS  Google Scholar 

  29. Schmidt D, Shorvon S (1996) The Epilepsies. In: T Brandt, LR Caplan, J Dichgans, H-CH Diener, C Kennard (eds): Neurological disorders.Course and Treatment. Academic Press, San Diego, 159–182

    Google Scholar 

  30. König StA, Eiger CE, Vassella F, Schmidt D, Bergmann A, Boenigk HE, Despland PA, Genton P, Krämer G, Löscher W, Mayer T, Nau H, Schneble H, Siemes H, Stefan H, Wolf P (1998) Empfehlungen zu Blutuntersuchungen and klinischer Überwachung zur Früherkennung des Valproat-assoziierten Leberversagens. Schweizerische Ärztezeitung 79: 580–585

    Google Scholar 

  31. Dreifuss FE, Santilli N, Langer DH, Sweeny KP, Moline KA, Meander KB (1987) Valproic acid hepatic fatalities: a retrospective review. Neurology 37: 397–400

    Google Scholar 

  32. Dreifuss FE, Langer DH, Moline KA, Maxwell JE (1989) Valproic acid hepatic fatalities. III. US experience since 1984. Neurology 39: 201— 207

    PubMed  Google Scholar 

  33. Jeavons PM, Clark JE (1974) Sodium valproate in treatment of epilepsy. Brit Med J 2: 584–586

    Article  PubMed  CAS  Google Scholar 

  34. Loyning Y, Johannessen SI, Ritland LS, Strandjord RE, Koster R (1982) Cases of serious/fatal hepatotoxicity due to valproate.Recommended control scheme and preliminary results. In: J Oxley, D Janz, H Meinardi (eds): Chronic Toxicity ofAntiepileptic Drugs. Raven Press, New York, 47–70

    Google Scholar 

  35. Stenzel E, Albani M, Doose H, Penin H, Scheffner D, Schmidt D (1987) Valproat-Therapie and Lebertoxizität. Pädiatr Prax 35: 159–163

    Google Scholar 

  36. Pellock JM, Willmore LJ (1991) A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 41: 961–964

    Article  PubMed  CAS  Google Scholar 

  37. Camfield C, Camfield P, Smith E, Tibbles JA (1996) Asymptomatic children with epilepsy: little benefit from screening anticonvulsant-induced liver, blood, or renal damage. Neurology 36: 838–841

    Article  Google Scholar 

  38. Fenichel GM, Greene HL (1985) Valproate hepatotoxicity: two new cases, a summary of others, and recommendations. Pediatr Neurol 1: 109–113

    Article  PubMed  CAS  Google Scholar 

  39. Erasmus C, Hjelm M,Wilson J (1983) The value of routine liver function monitoring during sodium valproate therapy. Br J Clin Pract 727 Suppl: 77–78

    Google Scholar 

  40. Silberstein SD,Willmore LJ (1996) Divalproex Sodium: Migraine Treatment and Monitoring. Headache 239–242

    Google Scholar 

  41. Ware S, Milliward-Sadler GH (1980) Acute liver disease associated with sodium valproate Lancet 17: 1110–1113

    Google Scholar 

  42. Appleton RE, Farell K, Applegarth DA, Dimmik JE, Wong LTK, Davidson AGF (1990) The high incidence of valproate hepatotoxicity may relate to familial metabolic defects. Can J Neurol Sci 17: 145–148

    CAS  Google Scholar 

  43. Harding BN, Egger J, Portmann B, Erdohazi M (1986) Progressive neuronal degeneration of childhood with liver disease. Brain 109: 181–206

    Article  PubMed  Google Scholar 

  44. Zäh W, Rengeling M, Rühl G, Hackenberg K (1985) Akute Lebernekrose durch Valproinat. Dtsch med Wschr 110: 956–959

    Article  PubMed  Google Scholar 

  45. Williams R (1982) Hepatic Disorders: Discussion. In: J Oxley, D Janz, H Meinardi (eds): Chronic Toxicity ofAntiepileptic Drugs. Raven Press, New York, 79–84

    Google Scholar 

  46. Tredger JM, Sherwood RA (1997) The liver. New functional, prognostic and diagnostic tests. Ann Clin Biochem 34: 121–141

    PubMed  Google Scholar 

  47. Schmidt D, Krämer G (1994) The New Antiepileptic Drugs. Implications for Avoidance of Adverse Effects. Drug Safety 11: 422–431

    Article  PubMed  CAS  Google Scholar 

  48. Tiagabin-Product Monograph, Novo-Nordisk, Mainz, Germany

    Google Scholar 

  49. Powell-Jackson PR,Tredger JM,Williams R (1984) Hepatotoxicity to sodium valproate: a review. Gut 25: 673–681

    Article  PubMed  CAS  Google Scholar 

  50. Straßburg HM, Sauer M, Ketelsen UP, Böhm N, Schwab M, Volk B (1990) Letale Valproat Unverträglichkeit bei progressiver zerebraler Poliodystrophie Alpers. In: J Lütschg (ed): Aktuelle Neuropädiatrie 1990. Springer-Verlag, Berlin, 258–263

    Google Scholar 

  51. Dodson WE (1997) Discussion. In: D Schmidt, E Perucca (eds): The place of felbamate in the treatment of Lennox-Gastaut Syndrome: an update. Proceedings of a meeting; 1997 April 22–23: Düsseldorf (Germany). s’Hertogenbosch,The Netherlands: Vanzuiden Comm, 8

    Google Scholar 

  52. Schwabe MJ, Dobyns WB, Burke B, Armstrong DL (1997) Valproate-induced liver failure in one of two siblings with Alpers disease. Ped Neurol 16: 337–343

    Article  CAS  Google Scholar 

  53. Njolstad PR, Skjeldal OH, Agsteribbe E, Huckriede A, Wannag E, Sovik O, Waaler PE (1997) Medium chain acyl-CoA dehydrogenase deficiency and fatal valproate toxicity. Pediatr Neurol 16: 160–162

    Article  PubMed  CAS  Google Scholar 

  54. O’Neil MG, Perdun CS, Wilson MB, McGown ST, Patel S (1996) Felbamate-associated fatal acute hepatic necrosis. Neurology 46:1457–1459

    Article  PubMed  Google Scholar 

  55. Morselli PL, Lloyd KG, Palminteri R (1995) Progabide. In: RH Levy, RH Mattson, BS Meldrum (eds): Antiepileptic Drugs,Fourth Edition. Raven Press, New York, 997–1009

    Google Scholar 

  56. Asconape JJ, Penry JK, Dreifuss FE, Rida A, Mirza W (1993) Valproate-associated pancreatitis. Epilepsia 34: 177–183

    Article  PubMed  CAS  Google Scholar 

  57. Zenker M, Metzker M, Wegener E, Heidemann PH (1995) Valproat-induzierte Pankreatitis. Monatsschr Kinderheilkd 143: 843–846

    Google Scholar 

  58. Gidal B, Spencer N, Maly M, Pitterle M, Williams E, Collins M, Jones J (1994) Valproatemediated disturbances of hemostasis: Relationship to dose and plasma concentration. Neurology 44: 1418–1422

    Article  PubMed  CAS  Google Scholar 

  59. Tennis P, Stern RS (1997) Risk of serious cutaneous disorders after initiation of use of phenytoin, carbamazepine, or sodium valproate: a record linkage study. Neurology 49: 542–546

    Article  PubMed  CAS  Google Scholar 

  60. Richens A, Davidson DLW, Cartlidge NEF, Easter DJ, The Adult EPITEG Collaborative Group (1994) A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. JNeurol Neurosurg Psychiatry 57: 682–687

    Article  CAS  Google Scholar 

  61. Carney P, Nasereddine W, Drury I, Varma N, Payne T, Shu V, Beydoun A (1997) Relation between thrombocytopenia and valproate dose. Epilepsia 38; Supp18: 102

    Google Scholar 

  62. Bottom KS, Adams DM, Mann KP, Ware RE (1997) Trilineage hematopoietic toxicity associated with valproic acid therapy. J Ped Hematol Oncol 19: 73–76

    Article  CAS  Google Scholar 

  63. Anderson GD, Lin Y-X, Berge C, Ojemann GA (1997) Absence of bleeding complications in patients undergoing cortical surgery while receiving valproate treatment. J Neurosurg 87: 252–256

    Article  PubMed  CAS  Google Scholar 

  64. Stahl MM, Neiderud J, Vinge E (1997) Thrombocytopenic purpura and anemia in a breast- fed infant whose mother was treated with valproic acid. J Pediatrics 130: 1001–1003

    Article  CAS  Google Scholar 

  65. Sasso E, Delsoldato S, Negrotti A, Mancia D (1994) Reversible valproate-induced extrapyramidal disorders. Epilepsia 35: 391–393

    Article  PubMed  CAS  Google Scholar 

  66. Zaret BS, Cohen RA (1986) Reversible valproic acid-induced dementia: a case report. Epilepsia 27: 234–240

    Article  PubMed  CAS  Google Scholar 

  67. Mantelet S, Gremion J, Feline A, Masnou P (1997) Valproate-associated encephalopathy: A case report. Review of the literature. Ann Med Psycholog 155: 510–512

    Google Scholar 

  68. Bauer J, Eiger CE (1993) Die akute Valproinsäure-Enzephalopathie. Akt Neurol 20: 16–21

    Article  Google Scholar 

  69. Bauer J (1996) Seizure-inducing effects of antiepileptic drugs: a review. Acta Neurol Scand 94: 367–377

    Article  PubMed  CAS  Google Scholar 

  70. Chadwick DW, Cumming WJK, Livingstone I, Cartlidge NEF (1979) Acute intoxication with sodium valproate. Ann Neurol 6: 552–553

    Article  PubMed  CAS  Google Scholar 

  71. Horiuchi M, Imamura Y, Nakamura N, Maruyama I, Saheki T (1993) Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid. J lnheri Metab Dis 16: 39–45

    Article  CAS  Google Scholar 

  72. Jones GL, Matsuo F, Baringer JR, Reichert WH (1990) Valproic acid-associated encephalopathy. West J Med 153: 199–202

    CAS  Google Scholar 

  73. Zaccara G, Paganini M, Campostrini R, Arnetoli G, Zappoli R, Moroni F (1984) Hyperammonemia and valproate-induced alterations of the state of consciousness. Eur Neurol 23: 104–112

    Article  PubMed  CAS  Google Scholar 

  74. Triggs WJ, Gilmore RL, Millington DS, Cibula J, Bunch TS, Harman E (1997) Valproateassociated carnitine deficiency and malignant cerebral edema in the absence of hepatic failure. Int J Clin Pharmacol Therap 35: 353–356

    CAS  Google Scholar 

  75. Marescaux C, Warter JM, Micheletti G, et al (1982) Stuporous episodes during treatment with sodium valproate: report of seven cases. Epilepsia 23: 197–305

    Article  Google Scholar 

  76. Marescaux C, Warter JM, Brandt C, et al (1985) Adaption of hepatic ammonia metabolism after chronic valproate administration in epileptics treated with phenytoin. Eur Neurol 24: 191–195

    Article  PubMed  CAS  Google Scholar 

  77. Steinhoff BJ, Stodieck SR (1993) Temporary abolition of seizure activity by flumazenil in a case of valproate-induced non-convulsive status epilepticus. Seizure 2: 261–265

    Article  PubMed  CAS  Google Scholar 

  78. Lam CW, Lau CH, Williams JC, Chan YW, Wong LJC (1997) Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr 156: 562–564

    Article  PubMed  CAS  Google Scholar 

  79. Melegh B, Trombitas K (1997) Valproate treatment induces lipid globule accumulation with ultrastructural abnormalities of mitochondria in skeletal muscle. Neuropediatr 28: 257–261

    Article  CAS  Google Scholar 

  80. Papzian O, Canizales E, Alfonso I, Archila R, Duchowny M, Aicardi J (1995) Reversible dementia and apparent brain atrophy during valproate therapy. Ann Neurol 38: 687–691

    Article  Google Scholar 

  81. Walstra GJ (1997) Reversible dementia due to valproic acid therapy. Ned Tijd Geneesk 141: 391–393

    CAS  Google Scholar 

  82. Guerrini R, Belmonte A, Canapicchi R, Casalini C, Perucca E (1998) Reversible pseudo-atrophy of the brain and mental deterioration associated with valproate treatment. Epilepsia 39: 27–32

    Article  PubMed  CAS  Google Scholar 

  83. Schöndienst M (1988) Hirnatrophien durch Valproat. Vier Fallberichte Epilepsie-Blätter 1: 23 (Abstract)

    Google Scholar 

  84. Froomes PR, Stewart MR (1994) A reversible parkinsonian syndrome and hepatotoxicity following addition of carbamazepine to sodium valproate. Aus New Zeal J Med 24: 413–414

    Article  CAS  Google Scholar 

  85. Park-Matsumoto YC, Tazawa T (1998) Valproate induced Parkinsonism. Brain Nerve 50: 81–84

    PubMed  CAS  Google Scholar 

  86. Wils V, Goluke-Willemse G (1997) Extrapyramidal syndrome due to valproate administration as an adjunct to lithium in an elderly manic patient. Int J Geriatric Psychiat 12: 272

    Article  CAS  Google Scholar 

  87. Armon C, Shin C, Miller P, Carwile S, Brown E, Edinger JD, Paul RG (1996) Reversible Parkinsonism and cognitive impairment with chronic valproate use. Neurology 47: 626–635

    Article  PubMed  CAS  Google Scholar 

  88. Trimble M (1991) The psychoses of epilepsy. Wrightson, London

    Google Scholar 

  89. Herranz JL, Arteaga R, Armijo JA (1982) Side-effects of sodium valproate in monotherapy controlled by plasma levels; a study in 88 pediatric patients. Epilepsia 23: 203–214

    Article  PubMed  CAS  Google Scholar 

  90. Vermeulen J, Aldenkamp AP (1995) Cognitive side-effects of chronic antiepileptic drug treatment. A review of 25 years of research. Epilepsy Res 22: 65–95

    Article  PubMed  CAS  Google Scholar 

  91. Vining EP, Mellitis ED, Dorsen MM, Freeman JM, et al (1987) Psychologic and behavioral effects of antiepileptic drugs in children: a double-blind comparison between phenobarbital and valproic acid. Pediatrics 80: 165–174

    PubMed  CAS  Google Scholar 

  92. Meador KJM, Loring DW, Huh K, et al. (1990) Comparative cognitive effects of anticonvulsants. Neurology 40: 391–394

    Article  PubMed  CAS  Google Scholar 

  93. Forsythe I, Butler R, Berg I, et al (1991) Cognitive impairment in new case of epilepsy randomly assigned to carbamazepine, phenytoin and sodium valproate. Dev Med Child Neurol 33: 524–534

    Article  PubMed  CAS  Google Scholar 

  94. Calandre EP, Dominguez-Granados R, Gomez-Rubio M, et al (1990) Cognitive effects of long-term treatment with phenobarbital and valproic acid in school children. Acta Neurol Scand 81: 504–506

    Article  PubMed  CAS  Google Scholar 

  95. Helmstaedter C, Wagner G, Elger CE (1993) Differential effects of first antiepileptic drug application on cognition in lesional and non-lesional patients with epilepsy. Seizure 2: 125–130

    Article  PubMed  CAS  Google Scholar 

  96. Craig I, Tallis R (1994) Impact of valproate and phenytoin on cognitive function in elderly patients: results of a single-blind randomized comparative study. Epilepsia 35: 381–390

    Article  PubMed  CAS  Google Scholar 

  97. Tonnby B, Nilsson H, Aldenkamp AP, et al (1994) Withdrawal of antiepileptic medication in children — correlation of cognitive function and plasma concentration — The multicentre “Holmfrid” study. Epilepsy Res 19: 141–152

    Article  PubMed  CAS  Google Scholar 

  98. Brouwer OF, Pieters MSM, Bakker AM, et al (1992) Conventional and controlled release valproate in children with epilepsy: a cross-over study comparing plasma levels and cognitive performance. Epilepsy Res 13: 245–253

    Article  PubMed  CAS  Google Scholar 

  99. Nicklas WJ, Vyas I, Heikkila RE (1985) Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of neurotoxic 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine. Life Sci 36: 2503–2508

    Article  PubMed  CAS  Google Scholar 

  100. Di Mauro S, Bonilla E, Zeviani M, Nakagawa M, De Vivo DC (1985) Mitochondrial myopathies. Ann Neurol 17: 521–538

    Article  Google Scholar 

  101. Hassan MN, Laljee HCK, Parsonage MJ (1976) Sodium valproate in the treatment of resistant epilepsy. Acta Neurol Scand 54: 209–218

    Article  PubMed  CAS  Google Scholar 

  102. Egger J, Brett EM (1981) Effects of sodium valproate in 100 children with special reference to weight. Br Med J 283:577–581

    Article  CAS  Google Scholar 

  103. Corman CL, Leung NM, Guberman AH (1997) Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci 24: 240–244

    PubMed  CAS  Google Scholar 

  104. Brodersen R, Jorgensen N, Vorum H, Krukow N (1990) Valproate and palmitate binding to human serum albumin: An hypothesis on obesity. Mol Pharmacol 37: 704–709

    PubMed  CAS  Google Scholar 

  105. Easter D, O’Bryan-Tear CG, Verity C (1997) Weight gain with valproate or carbamazepine —A reappraisal. Seizure 6: 121–125

    Article  PubMed  CAS  Google Scholar 

  106. Herzog AG (1993) A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy. Neurology 43: 1907–1910

    Article  PubMed  CAS  Google Scholar 

  107. Isojärvi JIT, Laatikainen TJ, Pakarinen AJ, Juntunen KT, Myllylä VV (1993) Polycystic ovaries and hyperandrogenism in woman taking valproate for epilepsy. N Engl J Med 329: 1383–1388

    Article  Google Scholar 

  108. Isojärvi JIT, Tauboll E, Dale PO, Rättyä J, Harbo HF, Gjerstad L, Myllylä VV, Tapanainen J (1997) Polycystic ovaries in woman taking valproate monotherapy for epilepsy: a two-center study. Epilepsia 38; Suppl 8: 102

    Google Scholar 

  109. Tauboll E, Isojärvi JIT, Harbo HF, Pakarinen AJ, Gjerstad L (1997) Changes in sex-steroid hormone levels and ovarian structure after valproate treatment in female rats. Epilepsia 38; Suppl 8: 47

    Google Scholar 

  110. Isojärvi JIT, Rättyä J, Myllylä VV, Knip A, Koivunen R, Pakarinen AJ, Tekay A, Tapanainen (1998) Valproate, lamotrigine, and insulin mediated risk in women with epilepsy. Ann Neurol 43: 446–451

    Article  PubMed  Google Scholar 

  111. Moller DE, Flier JS (1991) Insulin resistance —mechanisms, syndromes, and implications. N Engl J Med 325: 938–948

    Article  CAS  Google Scholar 

  112. Curtis VL, Oelberg DG, Willmore Li (1994) Infertility secondary to valproate. J Epilepsy 7: 259–261

    Article  Google Scholar 

  113. Nag D, Garg RK, Banerjee A (1997) Sodium valproate monotherapy and sex hormones in men. Neurology India 45: 240–243

    Google Scholar 

  114. Asconapé JJ, Manning KR, Lancman ME (1994) Systemic lupus erythematosus associated with use of valproate. Epilepsia 35: 162–163

    Article  PubMed  Google Scholar 

  115. Branten AJ, Wetzels JF, Weber AM, Koene RA (1998) Hyponatremia due to sodium valproate. Ann Neurol 43: 256–257

    Article  Google Scholar 

  116. Ryan SJ, Bishof NA, Baumann RJ (1996) Occurrence of renal Fanconi syndrome in children on valproic acid therapy. J Epilepsy 9: 35–38

    Article  Google Scholar 

  117. Gidal BE, Inglese CM, Meyer JF, Pitterle ME, Antonopolous J, Rust RS (1997) Diet-and valproate-induced transient hyperammonemia: effect of L-carnitine. Ped Neurol 16: 301–305

    Article  CAS  Google Scholar 

  118. Batshaw ML, Brusilow SW (1982) Valproate-induced hyperammonaemia. Ann Neurol 11: 319–321

    Article  PubMed  CAS  Google Scholar 

  119. Bohles H, Sewell AC, Wenzel D (1996) The effect of carnitine supplementation in valproate-induced hyperammonaemia. ACTA Paediatr Int J Paediatr 85: 446–449

    Article  CAS  Google Scholar 

  120. Warner MH, Anderson GD, McCarty JP, Farwell JR (1997) Effect of carnitine on measures of energy levels, mood, cognition, and sleep in adolescents with epilepsy treated with valproate. J Epilepsy 10: 126–130

    Article  Google Scholar 

  121. Anderson HH, Rapley JW, Williams DR (1997) Gingival overgrowth with valproic acid: a case report [Review] [20 ref]. ASDC J Dent Child 64: 294–297

    CAS  Google Scholar 

  122. Lortie A, Chiron C, Mumford J, Dulac O (1993) The potential for increasing seizure frequency, relapse, and appearance of new seizure types with vigabatrin. Neurology 43: S24—S27

    PubMed  Google Scholar 

  123. Farrar HC, Herold DA, Reed MD (1993) Acute valproic acid intoxication: Enhanced drug clearence with oral-activated charcoal. Crit Care Med 21: 299–301

    Article  PubMed  CAS  Google Scholar 

  124. Pertoldi F, D’Orlando F, Galliazzo S, Mercante WP (1997) Haemodialysis in the management of severe valproic acid overdose. Clin Intensive Care 8: 244–246

    Google Scholar 

  125. Matsumoto J, Ogawa H, Maeyama R, Okudaira, K Shinka T, Kuhara T, Matsumoto I (1997) Successful treatment by direct hemoperfusion of coma possibly resulting from mitochondrial dysfunction in acute valproate intoxication. Epilepsia 38: 950–953

    Article  PubMed  CAS  Google Scholar 

  126. Krämer G (1998) Epilepsien im höheren Lebensalter. Klinik und Besonderheiten der Pharmakotherapie. Thieme, Stuttgart

    Google Scholar 

  127. Sanofi-Winthrop, Paris, Corporate Data Sheet (1997) Sodium valproate

    Google Scholar 

  128. Hansten PD, Horn JR (1997) Hanston and Horn’s drug interactions analysis and management. Applied Therapeutics, Vancouver

    Google Scholar 

  129. Krämer G (1992) Medikamentöse Interaktionen von Antiepileptika. In: HC Hopf, P Poeck, H Schliak (eds): Neurologie in Klinik und Praxis,Band 1, 2. Auflage. Thieme Verlag, Stuttgart, 3: 94–97

    Google Scholar 

  130. Krämer G (1994) Interaktionen. In: Fröscher W, Vassella F (eds): Die Epilepsien. Grundlagen, Klinik, Behandlung. de Gruyter, Berlin, 545–551

    Google Scholar 

  131. Krämer G (1997) Interaktionsmatrix Antiepileptika. Wechselwirkungen komprimiert. Mediamed,Berkheim

    Google Scholar 

  132. Krämer G (1998) Pharmacokinetic interactions of the new antiepileptic drugs. In: H Stefan, G Krämer, B Mamoli (eds): Challenge epilepsy. New Antiepileptic drugs. Blackwell Wissenschafts-Verlag, Berlin, 87–103

    Google Scholar 

  133. Krämer G, Besser R, Theisohn M (1987) Interaktionen von Carbamazepin mit anderen Medikamenten. In: G Krämer, HC Hopf (eds): Carbamazepin in der Neurologie Thieme Verlag, Stuttgart, 70–90

    Google Scholar 

  134. Ouslander JG (1981) Drug therapy in elderly. Ann Intern Med 95: 711–722

    PubMed  CAS  Google Scholar 

  135. Pitlick WH (ed) (1989) Antiepileptic Drug interactions. Demos, New York

    Google Scholar 

  136. Rambeck B, Krämer G (1992) Medikamentöse Interaktionen von und mit Valproinsäure. In: G Krämer, M Laub (eds): Valproinsäure. Pharmakologie, klinischer Einsatz, Nebenwirkungen, Therapierichtlinien. Springer Verlag, Berlin 106–112

    Google Scholar 

  137. Bernus I, Dickinson RG, Hooper WD, Eadie MJ (1994) Inhibition of phenobarbitone N-glucosidation by valproate. Br J Clin Pharmacol 38: 411–416

    Article  PubMed  CAS  Google Scholar 

  138. Yuen AW, Land G, Weatherley BC, Peck AW (1992) Sodium valproate acutely inhibits lamotrigine metabolism. Br J Clin Pharm 33: 511–513

    Article  CAS  Google Scholar 

  139. Messenheimer J, Mullens EL, Giorgi L, Young F (1998) Safety review of adult clinical trial experience with lamotrigine. Drug Safety 18: 281–296

    Article  PubMed  CAS  Google Scholar 

  140. Fitton A, Goa KL (1995) Lamotrigine: an update of its pharmacology and therapeutic use in epilepsy. Drugs 50: 691–713

    Article  PubMed  CAS  Google Scholar 

  141. GlaxoWellcome (1998) Lamictal Monograph. London,1997

    Google Scholar 

  142. Lai M-L, Huang JD (1993) Dual effect of valproic acid on the pharmacokinetics of phenytoin. Biopharm Drug Dis 14: 365–370

    Article  CAS  Google Scholar 

  143. Ramsay RE, McManus DQ, Guterman A, Briggle TV, Vazquez D, Perchalski R, Yost RA, Wong P (1990) Carbamazepine metabolism in humans: Effect of concurrent anticonvulsant therapy. Ther Drug Monit 12: 235–241

    Article  PubMed  CAS  Google Scholar 

  144. Bernus I, Dickinson G, Hooper WE, Eadie MJ (1997) The mechanism of the carbamazepine-valproate interaction in humans. Br J Clin Pharmacol 44: 21–27

    Article  PubMed  CAS  Google Scholar 

  145. Svinarov DA, Pippenger CE (1995) Valproic acid-carbamazepine interaction: Is valproic acid a selective inhibitor of epoxide hydrolase? Ther Drug Monit 17: 217–220

    Article  PubMed  CAS  Google Scholar 

  146. Liu H, Delgado MR, Browne RH (1995) Interactions of valproic acid with carbamazepine and ist metabolites’ concentrations, concentration ratios and level/dose ratios in epileptic children. Clin Neuropharm 18: 1–12

    Article  Google Scholar 

  147. Anderson GD, Gidal BE, Kantor ED, Wilensky AJ (1994) Lorazepam-valproate interaction: Studies in normal subjects and isolated perfused rat liver. Epilepsia 35: 221–225

    Article  PubMed  CAS  Google Scholar 

  148. Samara EE, Granneman RG, Witt GF, Cavanaugh JH (1997) Effect of valproate on the pharmacokinetics and pharmacodynamics of lorazepam. J Clin Pharmacol 37: 442–450

    PubMed  CAS  Google Scholar 

  149. Wong SL, Cavanaugh JH, Shi H, Awni WM, Granneman GR (1996) Effects of divalproex sodium on amitriptyline and nortriptyline pharmacokinetics. Clin Pharmacol Ther 60: 48–53

    Article  PubMed  CAS  Google Scholar 

  150. De Toledo JC, Haddad H, Ramsay RE (1997) Status epilepticus associated with the combination of valproic acid and clomipramine. Ther Drug Monitor 19: 71–73

    Article  Google Scholar 

  151. Akula SK, Rege AB, Dreisbach AW, Dejace PMJT, Lertora JJL (1997) Valproic acid increases cerebrospinal fluid zidovudine levels in a patient with AIDS. Am J Med Sci 313: 244–246

    Article  PubMed  CAS  Google Scholar 

  152. Lertora JJL, Rege AB, Greespan DL, Akula S, George WJ, Hyslop NE, Agrawal KC (1994) Pharmacokinetic interaction betweeen zidovudine and valproic acid in patients infected with human immunodeficiency virus. Clin Pharmacol Ther 56: 272–278

    Article  PubMed  CAS  Google Scholar 

  153. Parmeggiani A, Riva R, Posar A, Rossi PG (1995) Possible interaction between acyclovir and antiepileptic treatment. Ther Drug Monitor 17: 312–315

    Article  CAS  Google Scholar 

  154. Pisani F (1992) Influence of co-medication on the metabolism of valproate. Pharm Weekbl Sci Ed 14: 108–113

    Article  CAS  Google Scholar 

  155. Spina E, Pisani F, Perucca E (1996) Clinically significant pharmacokinetic drug interactions with carbamazepine. An update. Clin Pharmacokinetics 31: 198–214

    Article  CAS  Google Scholar 

  156. Jann MW, Fidone GS, Israel MK, Bonadero P (1988) Increased valproate serum concentrations upon carbamazepine cessation. Epilepsia 29: 578–581

    Article  PubMed  CAS  Google Scholar 

  157. Gustayson LE, Cato A, Guenther HJ, et al (1995) Lack of clinically important drug interactions between tiagabine and carbamazepine, phenytoin or valproate. Epilepsia 36 (Supp13): S159—S 160

    Google Scholar 

  158. Anderson GD, Yau MK, Gidal BE, Harris SJ, Levy RH, Lai AA, Wolf KB, Wargin WA, Dren AT (1996) Bidirectional interaction of valproate and lamotrigine in healthy subjects. Clin Pharm Ther 60: 145–156

    Article  CAS  Google Scholar 

  159. Salke-Kellermann RA, May T, Boenigk HE (1997) Influence of ethosuximide on valproic acid serum concentrations. Epilepsia Res 26: 345–349

    Article  CAS  Google Scholar 

  160. Nagai K, Shimizu T, Togo A, Takeya M, Yokomizo Y, Sakata Y, Matsuishi T, Kato H (1997) Decrease in serum levels of valproic acid during treatment with a new carbapenem, panipenem/betamipron [8]. J Antimicro Chemother 39: 295–296

    Article  CAS  Google Scholar 

  161. Duncan JS, Patsalos PN, Shorvon SD (1991) Effects of discontinuation of phenytoin, carbamazepine, and valproate on concomitant antiepileptic medication. Epilepsia 32: 101–115

    Article  PubMed  CAS  Google Scholar 

  162. Jonville AP Gauchez AS, Autret E, Billard C, Barbier P, Nsabiyumva F, Breteau M (1991) Interaction between isoniazid and valproate. A case of valproate overdosage [1]. Eur J Clin Pharm 40: 197–198

    CAS  Google Scholar 

  163. Perucca E (1996) Establised antiepileptic drugs. In: MJ Brodie, DM Treiman (eds) Modern Management of epilepsy. Baillière’s Clinical Neurology International practice and research. Baillière Tindall, London, 693–722

    Google Scholar 

  164. Hooper WD, Franklin Me, Glue P Banfield CR, Radwanski E, Mc Laughlin DB, McIntyre ME, Dickinson RG, Eadie MJ (1996) Effect of felbamate on valproic acid disposition in healthy volunteers: inhibition of beta-oxidation. Epilepsia 37: 91–97

    Article  PubMed  CAS  Google Scholar 

  165. Wagner ML, Graves NM, Leppik IE, Remmel RP, Shumaker RC, Ward DL, Perhach JL (1994) The effect of felbamate on valproic acid disposition. Clin Pharmacol Ther 56: 494–502

    Article  PubMed  CAS  Google Scholar 

  166. Felbamate Core Product Information (1998) Schering-Plough

    Google Scholar 

  167. Gustayson LE, Cato A, Guenther HJ, et al (1995) Lack of clinically important drug interactions between tiagabine and carbamazepine, phenytoin or valproate. Epilepsia 36 (Suppl 3): S159—S160

    Google Scholar 

  168. Robert E, Guibaud P (1982) Maternal valproic acid and congenital neural defects. Lancet 2: 1142

    Google Scholar 

  169. Lindhout D, Omtzigt JGC (1992) Pregnancy and the risk of teratogenicity. Epilepsia 33 (Suppl 4) S41—S48

    PubMed  Google Scholar 

  170. Janz D, Dam M, Richens A, Bossi L, Helge H, Schmidt D (eds) (1982) Epilepsy, pregnancy and the child. Raven Press, New York

    Google Scholar 

  171. Centers for Disease Control (1983) Valproate: a new cause of birth defects - report from Italy and follow up from France. Morbidity and Motality Weekly Report 32: 438–439

    Google Scholar 

  172. Samren EB, van Duijn CM, Koch S, Hiilesmaa VK, Klepel H, Bardy AH, Beck-Mannagetta G, Deichl AW, Gaily E, Granstrom ML, Meinardi H, Grobbee DE, Hofman A, Janz D, Lindhout D (1997) Maternal use antiepileptic drugs and the risk of major congenital malformations: A joint European prospective study of human teratogenesis associated with maternal epilepsy. Epilepsia 38: 981–990

    Article  PubMed  CAS  Google Scholar 

  173. Omtzigt JGC, Los FJ, Grobbee DE, Pijpers L, Jahoda MGJ, Brandenburg H, Stewart PA, Gaillard HLJ, Sachs ES, Wladimiroff JW, Lindhout D (1992) The risk of spina bifida aperta after first-trimester exposure to valproate in a prenatal cohort. Neurology 42: 119–125

    PubMed  CAS  Google Scholar 

  174. MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the MRC Vitamin Study. Lancet 338: 132–37

    Google Scholar 

  175. Elmazar MM, Thiel R, Nau H (1992) Effect of supplementation with folinic acid, vitamin B6, and vitamin B12 on valproic acid-induced teratogenesis in mice. Fund App Toxicol 18: 389–394

    Article  CAS  Google Scholar 

  176. Hansen DK, Grafton TF (1991) Lack of attenuation of valproic acid-induced effects by folinic acid in rat embryos in vitro. Teratology 43: 575–582

    Article  PubMed  CAS  Google Scholar 

  177. Hansen DK, Grafton TF, Dial SL, Gehring TA, Siitonen PH (1995) Effect of supplemental folic acid on valproic acid-induced embryotoxicity and tissue zinc levels in vivo. Teratology 52: 277–285

    Article  PubMed  CAS  Google Scholar 

  178. Wilcken DE (1997) MTHFR 677 »T mutation, folate intake, neural-tube defect, and risk of cardiovascular disease. Lancet 350: 603–604

    Article  PubMed  CAS  Google Scholar 

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  1. Epilepsy Research Group, Goethestrasse 5, D-14163, Berlin, Germany

    Dieter Schmidt

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  1. Department of Pharmacology, Toxicology, and Pharmacy, School of Veterinary Medicine, BĂĽnteweg 17, Bldg. 225, D-30559, Hannover, Germany

    Wolfgang Löscher

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Schmidt, D. (1999). Adverse effects and interactions with other drugs. In: Löscher, W. (eds) Valproate. Milestones in Drug Therapy. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8759-5_10

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  • DOI: https://doi.org/10.1007/978-3-0348-8759-5_10

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