Skip to main content
Log in

Umstellungen zwischen Lamotrigin-Präparaten bei Epilepsiepatienten

Erfahrungen einer universitären Epilepsieambulanz

Changing lamotrigine preparations in epilepsy patients

Experiences of a university epilepsy outpatient centre

  • Originalien
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Die zunehmende Verfügbarkeit von Generika auch bei Antikonvulsiva der 2. Generation hat zu einer Diskussion über mögliche Kostenersparnis einerseits und mögliche Verschlechterung der Effektivität und Verträglichkeit einer etablierten Epilepsietherapie andererseits geführt. In der hier vorgestellten retrospektiven Analyse bei ambulant mit Lamotrigin behandelten Patienten werden die Häufigkeit mit einer behandelnden Epilepsieambulanz nicht abgesprochener Umstellungen und ihre Auswirkungen auf die Anfallskontrolle und Verträglichkeit der Therapie analysiert. Bei 13 von 285 mit Lamotrigin behandelten Patienten wurde ein Präparatewechsel vorgenommen, hierbei kam es bei 6 Patienten zu einem Anfallsrezidiv nach 3-monatiger bis 6-jähriger Anfallsfreiheit, 3 Patienten litten unter neu auftretenden Nebenwirkungen. Im Vergleich zu einer gematchten Kontrollgruppe war das relative Risiko für einen Verlust der Anfallskontrolle 17fach, für Nebenwirkungen 3fach erhöht. Konsekutive Serumkonzentrationsbestimmungen weisen auf einen Zusammenhang mit einer veränderten Pharmakokinetik der Präparate hin. Die Häufigkeit dieser umstellungsassoziierten Probleme wird unter medizinischen und sozioökonomischen Gesichtspunkten diskutiert.

Summary

An increasing number of second-generation antiepileptic drugs have become available as generics. There is an ongoing debate as to whether this opens up ways to save costs or if efficacy and tolerability of an established treatment are at stake. We here present a retrospective analysis of outpatients treated with lamotrigine regarding the frequency of treatment switches and its effects on seizure control and tolerability. In 13 of 285 patients under treatment with lamotrigine the prescribed drug was changed; in 6 of these seizure relapse occurred after a period of 3 months to 6 years of seizure freedom and 3 patients experienced new side effects. Compared to matched controls, the risk for loss of seizure control was significantly elevated by a factor of 17; adverse events were three times more frequent (n.s.). Consecutive determinations of serum levels suggest that these problems were related to changes in the pharmacokinetics of different formulations. Frequent problems related to a switch of medication are discussed under medical and socio-economic aspects.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. American Academy of Neurology (1990) Assessment: generic substitution for antiepileptic medication. Report of the therapeutics and technology assessment subcommittee of the American academy of neurology. Neurology 11:1641–1643

    Google Scholar 

  2. Andermann F, Duh MS, Gosselin A et al (2007) Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes. Epilepsia 3:464–469

    Article  CAS  Google Scholar 

  3. Banahan BF, Bonnarens JK, Bentley JK (1998) Generic substitution of NTI drugs: issues for formulary committee consideration. Formulary 33:1082–1096

    Google Scholar 

  4. Berg MJ, Gross RA, Tomaszewski KJ et al (2008) Generic substitution in the treatment of epilepsy: case evidence of breakthrough seizures. Neurology 7:525–530

    Article  CAS  Google Scholar 

  5. Bialer M (2007) Generic products of antiepileptic drugs (AEDs): is it an issue? Epilepsia 10:1825–1832

    Article  Google Scholar 

  6. Crawford P, Feely M, Guberman A et al (2006) Are there potential problems with generic substitution of antiepileptic drugs? A review of issues. Seizure 3:165–176

    Article  Google Scholar 

  7. Crawford P, Hall WW, Chappell B et al (1996) Generic prescribing for epilepsy. Is it safe? Seizure 1:1–5

    Article  Google Scholar 

  8. Duh MS, Andermann F, Paradis PE et al (2007) The economic consequences of generic substitution for antiepileptic drugs in a public payer setting: the case of lamotrigine. Dis Manag 4:216–225

    Article  Google Scholar 

  9. Duh MS, Paradis PE, Latremouille-Viau D et al (2009) The risks and costs of multiple-generic substitution of topiramate. Neurology 24:2122–2129

    Article  CAS  Google Scholar 

  10. EMEA (2008) Guidelines for the investigation of bioequivalence. http://www.emea.europa.eu/pdfs/human/qwp/140198enrev1.pdf

  11. Epilepsy Foundation (2009) Epilepsy patients‘ experiences changing the formulation of the drugs they use to prevent seizures. http://www.epilepsyfoundation.org/medicationswitching/Consumer_Survey_Report_Recommendations.pdf

  12. FDA (1997) Criteria and evidence to assess actual or potential bioequivalence problems. The US code of federal regulations. 21 CFR 320. 33(C):206–207

  13. FDA (2008) Therapeutic equivalence of generic drugs – letter to health practitioners. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm073182.htm

  14. FDA (2009) Part 320 bioavailability and bioequivalence requirements 21CFR320.33. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=320.33

  15. Feely M, Crawford P, Krämer G et al (2005) Risk management in epilepsy: generic substitution and continuity of supply. Eur J Hosp Pharm Sci 11:83–87

    Google Scholar 

  16. Gilman JT, Alvarez LA, Duchowny M (1993) Carbamazepine toxicity resulting from generic substitution. Neurology 12:2696–2697

    Google Scholar 

  17. Heaney DC, Beran RG, Halpern MT (2002) Economics in epilepsy treatment choices: our certain fate? Epilepsia 32–38

  18. Jobst BC, Holmes GL (2004) Prescribing antiepileptic drugs: should patients be switched on the basis of cost? CNS Drugs 10:617–628

    Article  Google Scholar 

  19. Krämer G, Dennig D, Schmidt D (2005) Für die Ad Hoc Kommission der Deutschen Gesellschaft für Epileptologie. Generika in der Epilepsietherapie: was ist zu beachten? Akt Neurol 32:275–278

    Article  Google Scholar 

  20. Langdon EH (2008) Switching to generic: the need for physician and patient consent when substituting antiepileptic medication. J Contemp Health Law Policy 1:166–195

    Google Scholar 

  21. LeLorier J, Duh MS, Paradis PE et al (2008) Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting. Curr Med Res Opin 4:1069–1081

    Article  Google Scholar 

  22. Liow K, Barkley GL, Pollard JR et al (2007) Position statement on the coverage of anticonvulsant drugs for the treatment of epilepsy. Neurology 16:1249–1250

    Article  Google Scholar 

  23. MacDonald JT (1987) Breakthrough seizure following substitution of Depakene capsules (Abbott) with a generic product. Neurology 12:1885

    Google Scholar 

  24. Majkowski J, Lason W, Daniel W (2004) Brand-name and generic drugs in the treatment of epilepsy: biopharmaceutical, pharmacological, clinical and economic problems. Epileptologie 12:365–389

    Google Scholar 

  25. Makus KG, McCormick J (2007) Identification of adverse reactions that can occur on substitution of generic for branded lamotrigine in patients with epilepsy. Clin Ther 2:334–341

    Article  CAS  Google Scholar 

  26. Meyer MC, Straughn AB (1993) Biopharmaceutical factors in seizure control and drug toxicity. Am J Hosp Pharm 12[Suppl 5]:17–22

  27. Paradis PE, Latremouille-Viau D, Moore Y et al (2009) Projected economic impact of clinical findings of generic entry of topiramate on G4 European countries. Curr Med Res Opin 7:1793–1805

    Article  CAS  Google Scholar 

  28. Perucca E, Albani F, Capovilla G et al (2006) Recommendations of the Italian league against epilepsy working group on generic products of antiepileptic drugs. Epilepsia 16–20

  29. Pharma-Barometer (2009) GKV: Einsparungen durch Generika halten an. http://www.dasinnovativsteprodukt.com/501/index.php?id=1888

  30. Scottish Intercollegiate Guidelelines Network (2005) Diagnosis and management of epilepsy in adults: a national clinical guideline. http://www.sign.ac.uk/pdf/sign70.pdf

  31. Swedish Medical Product Agency (MPA) (2004) Neurontin och Gabapentin Nycomed – varför inte utbytbara? http://www.lakemedelsverket.se/Alla-nyheter/NYHETER–-2004/Neurontin-och-Gabapentin-Nycomed – varfor-inte-utbytbara/

  32. Tyrer JH, Eadie MJ, Sutherland JM et al (1970) Outbreak of anticonvulsant intoxication in an Australian city. Br Med J 5730:271–273

    Article  Google Scholar 

  33. Welty TE, Pickering PR, Hale BC et al (1992) Loss of seizure control associated with generic substitution of carbamazepine. Ann Pharmacother 6:775–777

    Google Scholar 

  34. Wilner AN (2004) Therapeutic equivalence of generic antiepileptic drugs: results of a survey. Epilepsy Behav 5:995–998

    Article  PubMed  Google Scholar 

  35. Wyllie E, Pippenger CE, Rothner AD (1987) Increased seizure frequency with generic primidone. JAMA 9:1216–1217

    Article  Google Scholar 

  36. Zachry WM III, Doan QD, Clewell JD et al (2009) Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes. Epilepsia 3:493–500

    Article  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. Carius.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carius, A., Schulze-Bonhage, A. Umstellungen zwischen Lamotrigin-Präparaten bei Epilepsiepatienten. Nervenarzt 81, 423–434 (2010). https://doi.org/10.1007/s00115-010-2933-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-010-2933-8

Schlüsselwörter

Keywords

Navigation