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Role of Liver Function Tests in Monitoring Anticonvulsant Use

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Abstract

Early investigations suggested the utility of routine monitoring of serum biochemistry to identify patients at risk for rare, idiosyncratic acute liver failure and other forms of serious hepatotoxicity associated with the use of anticonvulsants. Such monitoring became the standard recommendation. Clinical examination and serum biochemistry screening are standard practice before starting a patient on anticonvulsants. Patients with aggravated hepatic dysfunction or overt hepatic disease should not receive anticonvulsants associated with acute hepatic failure such as valproic acid (sodium valproate) or felbamate, and those at increased risk for acute hepatic failure should receive these drugs only after careful consideration of all the circumstances.

The available scientific evidence, however, does not support indiscriminate and repeated serum biochemistry monitoring for patients receiving anticonvulsants, mainly because moderate elevations of transaminase and alkaline phosphatase levels are common in asymptomatic patients receiving these drugs, and serum biochemistry changes are not always present in the early course of acute anticonvulsant-associated hepatic failure. Careful history-taking and notification of patients, caregivers and physicians of high risk groups and the warning symptoms and signs of incipient hepatic failure, such as decreased alertness, jaundice, vomiting, haemorrhage, increased frequency of seizures, anorexia and oedema, especially during the first 6 months of treatment, are the best methods for early detection.

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References

  1. Jeavons PM, Clarke JE. Sodium valproate in the treatment of epilepsy. BMJ 1974; 2: 584–6

    Article  PubMed  CAS  Google Scholar 

  2. Loyning Y, Johannessen SI, Ritland LS, et al. Cases of serious/fatal hepatotoxicity due to valproate: recommended control scheme and preliminary results. In: Oxley J, Janz D, Meinardi H, editors. Chronic toxicity of antiepileptic drugs. New York: Raven, 1982: 47–70

    Google Scholar 

  3. Stenzel E, Albani M, Doose H, et al. Valproat-Therapie und Lebertoxizität. Pädiatr Prax 1987; 35: 159–63

    Google Scholar 

  4. Physicians desk reference. 51st ed. Montvale (NJ): Medical Economics Company, 1997

  5. Pellock JM, Willmore LJ. A rational guide to routine blood monitoring in patients receiving antiepileptic drugs. Neurology 1991; 41: 961–4

    Article  PubMed  CAS  Google Scholar 

  6. Camfield C, Camfield P, Smith E, et al. Asymptomatic children with epilepsy: little benefit from screening anticonvulsant-induced liver, blood, or renal damage. Neurology 1996; 36: 838–41

    Article  Google Scholar 

  7. Fenichel GM, Greene HL. Valproate hepatotoxicity: two new cases, a summary of others, and recommendations. Pediatr Neurol 1985; 1: 109–13

    Article  PubMed  CAS  Google Scholar 

  8. Erasmus C, Hjelm M, Wilson J. The value of routine liver function monitoring during sodium valproate therapy. Br J Clin Pract 1983: 727 Suppl.: 77–8

    Google Scholar 

  9. Silberstein SD, Willmore LJ. Divalproex sodium: migraine treatment and monitoring. Headache 1996; 36(4):239–42

    Article  PubMed  CAS  Google Scholar 

  10. Callaghan N, Majeed T, O’Connell A, et al. Acomparative study of serum F protein and other liver function tests as an index of hepatocellular damage in epileptic patients. Acta Neurol Scand 1994; 89(4): 237–41

    Article  PubMed  CAS  Google Scholar 

  11. Schmidt D. Adverse effects of antiepileptic drugs. New York: Raven Press, 1982

    Google Scholar 

  12. Oxcarbazepine. Product monograph. Basle, Switzerland: Novartis, 1997

  13. Topamax. Product monograph. Cilag International, 1996

  14. Richens A. Lamotrigine: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 897–902

    Google Scholar 

  15. Schmidt D, Shorvon S. The epilepsies. In: Brandt T, Caplan LR, Dichgans J, et al., editors. Neurological disorders: course and treatment. San Diego (CA): Academic Press, 1996: 159–82

    Google Scholar 

  16. König StA, Elger CE, Vassella F, et al. Empfehlungen zu Blutuntersuchungen und klinischer Überwachung zur Früherkennung des Valproat-assoziierten Leberversagens. Nervenarzt. Schweiz Ärztezeitung 1998; 79(14): 580–5

    Google Scholar 

  17. Morselli PL, Lloyd KG, Palminteri R. Progabide. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 997–1009

    Google Scholar 

  18. Schmidt D, Krämer G. The new antiepileptic drugs: implications for avoidance of adverse effects. Drug Saf 1994; 11: 422–31

    Article  PubMed  CAS  Google Scholar 

  19. Tiagabine. Product monograph. Mainz: Novo-Nordisk, 1997

  20. Asconape JJ, Penry JK, Dreifuss FE, et al. Valproate-associated pancreatitis. Epilepsia 1993; 34: 177–83

    Article  PubMed  CAS  Google Scholar 

  21. Powell-Jackson PR, Tredger JM, Williams R. Hepatotoxicity to sodium valproate: a review. Gut 1984; 25: 673–81

    Article  PubMed  CAS  Google Scholar 

  22. Bryant AE, Dreifuss FE. Valproic acid hepatic fatalities: III. US experience since 1986. Neurology 1996; 46: 465–9

    Article  PubMed  Google Scholar 

  23. Dreifuss FE, Santilli N, Langer DH, et al. Valproic acid hepatic fatalities: a retrospective review. Neurology 1987; 37: 397–400

    Google Scholar 

  24. Dreifuss FE, Langer DH, Moline KA, et al. Valproic acid hepatic fatalities: III. US experience since 1984. Neurology 1989; 39: 201–7

    Article  PubMed  CAS  Google Scholar 

  25. Appleton RE, Farell K, Applegarth DA, et al. The high incidence of valproate hepatotoxicity may relate to familial metabolic defects. Can J Neurol Sci 1990; 17: 145–8

    PubMed  CAS  Google Scholar 

  26. Harding BN, Egger J, Portmann B, et al. Progressive neuronal degeneration of childhood with liver disease. Brain 1986; 109: 181–206

    Article  PubMed  Google Scholar 

  27. Strassburg HM, Sauer M, Ketelsen UP, et al. Letale Valproat-Unverträglichkeit bei progressiver zerebraler Poliodystrophie Alpers. In: Lütschg J, editor. Aktuelle Neuropädiatrie 1990. Berlin: Springer, 1990: 258–63

    Google Scholar 

  28. Dodson WE. Discussion. In: Schmidt D, Perucca E, editors. The place of felbamate in the treatment of Lennox-Gastaut syndrome: an update [abstract]. Proceedings of a meeting; 1997 Apr 22–23: Düsseldorf. sHertogenbosch: Vanzuiden Comm, 1997: 8

  29. Fisher RS, Kerrigan JF. Vigabatrin: toxicity. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 931–9

    Google Scholar 

  30. Data on file, Parke-Davis, 1993

  31. Ramsay RE. Clinical efficacy and safety of gabapentin. Neurology 1994; 44Suppl. 5: S23–30

    PubMed  CAS  Google Scholar 

  32. Vigabatrin. Product monograph. Bad Soden: Hoechst Marion Roussell, 1997

  33. Seino M, Naruto S, Ito T, et al. Zonisamide. In: Levy RH, Mattson RH, Meldrum BS, editors. Antiepileptic drugs. 4th ed. New York: Raven, 1995: 1011–23

    Google Scholar 

  34. Jeavons PM. Hepatotoxicity of antiepileptic drugs. In: Oxley J, Janz D, Meinardi H. Chronic toxicity of antiepileptic drugs. New York: Raven, 1982: 1–45

    Google Scholar 

  35. Scheffner D, König StA, Rauterberg-Ruland I, et al. Fatal liver failure in 16 children with valproate therapy. Epilepsia 1988; 29: 530–42

    Article  PubMed  CAS  Google Scholar 

  36. Siemes H, Nau H, Seidel U, et al. Irreversibles valproat-assoziiertes Leberversagen. Monatsschr Kinderheilkd 1992; 140: 869–75

    PubMed  CAS  Google Scholar 

  37. Suchy FJ, Balisteri WF, Buchino JJ, et al. Acute hepatic failure associated with the use of sodium valproate. N Engl J Med 1979; 300: 962–6

    Article  PubMed  CAS  Google Scholar 

  38. Zäh W, Rengeling M, Rühl G, et al. Akute Lebernekrose durch Valproinat. Dtsch Med Wochenschr 1985; 110: 956–9

    Article  PubMed  Google Scholar 

  39. O’Neil MG, Perdun CS, Wilson MB, et al. Felbamate-associated fatal acute hepatic necrosis. Neurology 1996; 46: 1457–9

    Article  PubMed  Google Scholar 

  40. Data on file. Kenilworth, USA: Schering-Plough, 1997

  41. Zimmerman HJ, Ishak KG. Valproate-induced hepatic injury: analysis of 23 fatal cases. Hepatology 1982; 2: 591–7

    Article  PubMed  CAS  Google Scholar 

  42. Yuen AWC, Bihari DJ. Multi-organ failure and disseminated intravascular coagulation in severe convulsive seizures [letter]. Lancet 1992; 340: 618

    Article  PubMed  CAS  Google Scholar 

  43. Ussery XT, Henar EL, Black DD, et al. Acute liver injury after protracted seizures in children. Pediatr Gastroenterol 1989; 9: 421–5

    Article  CAS  Google Scholar 

  44. Brown SW, Clarke MA, Tomlin PI. Fatal liver failure following generalized tonic-clonic seizures. Seizure 1992; 1: 75–7

    Article  PubMed  CAS  Google Scholar 

  45. Ware S, Milliward-Sadler GH. Acute liver disease associated with sodium valproate. Lancet 1980; II: 1110–3

    Article  Google Scholar 

  46. Williams R. Hepatic disorders: discussion. In: Oxley J, Janz D, Meinardi H, editors. Chronic toxicity of antiepileptic drugs. New York: Raven Press, 1982: 79–84

    Google Scholar 

  47. Tredger JM, Sherwood RA. The liver: new functional, prognostic and diagnostic tests. Ann Clin Biochem 1997; 34: 121–41

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Epilepsy Research Group Berlin, Berlin, Germany

    Dieter Schmidt & Hartmut Siemes

  2. Paediatric Clinic, DRK Kliniken Westend, Berlin, Germany

    Hartmut Siemes

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  1. Dieter Schmidt
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  2. Hartmut Siemes
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Correspondence to Dieter Schmidt.

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Schmidt, D., Siemes, H. Role of Liver Function Tests in Monitoring Anticonvulsant Use. Mol Diag Ther 10, 321–328 (1998). https://doi.org/10.2165/00023210-199810050-00002

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