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.
Literatur
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
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
Banahan BF, Bonnarens JK, Bentley JK (1998) Generic substitution of NTI drugs: issues for formulary committee consideration. Formulary 33:1082–1096
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
Bialer M (2007) Generic products of antiepileptic drugs (AEDs): is it an issue? Epilepsia 10:1825–1832
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
Crawford P, Hall WW, Chappell B et al (1996) Generic prescribing for epilepsy. Is it safe? Seizure 1:1–5
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
Duh MS, Paradis PE, Latremouille-Viau D et al (2009) The risks and costs of multiple-generic substitution of topiramate. Neurology 24:2122–2129
EMEA (2008) Guidelines for the investigation of bioequivalence. http://www.emea.europa.eu/pdfs/human/qwp/140198enrev1.pdf
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
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
FDA (2008) Therapeutic equivalence of generic drugs – letter to health practitioners. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/ucm073182.htm
FDA (2009) Part 320 bioavailability and bioequivalence requirements 21CFR320.33. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=320.33
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
Gilman JT, Alvarez LA, Duchowny M (1993) Carbamazepine toxicity resulting from generic substitution. Neurology 12:2696–2697
Heaney DC, Beran RG, Halpern MT (2002) Economics in epilepsy treatment choices: our certain fate? Epilepsia 32–38
Jobst BC, Holmes GL (2004) Prescribing antiepileptic drugs: should patients be switched on the basis of cost? CNS Drugs 10:617–628
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
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
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
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
MacDonald JT (1987) Breakthrough seizure following substitution of Depakene capsules (Abbott) with a generic product. Neurology 12:1885
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
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
Meyer MC, Straughn AB (1993) Biopharmaceutical factors in seizure control and drug toxicity. Am J Hosp Pharm 12[Suppl 5]:17–22
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
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
Pharma-Barometer (2009) GKV: Einsparungen durch Generika halten an. http://www.dasinnovativsteprodukt.com/501/index.php?id=1888
Scottish Intercollegiate Guidelelines Network (2005) Diagnosis and management of epilepsy in adults: a national clinical guideline. http://www.sign.ac.uk/pdf/sign70.pdf
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/
Tyrer JH, Eadie MJ, Sutherland JM et al (1970) Outbreak of anticonvulsant intoxication in an Australian city. Br Med J 5730:271–273
Welty TE, Pickering PR, Hale BC et al (1992) Loss of seizure control associated with generic substitution of carbamazepine. Ann Pharmacother 6:775–777
Wilner AN (2004) Therapeutic equivalence of generic antiepileptic drugs: results of a survey. Epilepsy Behav 5:995–998
Wyllie E, Pippenger CE, Rothner AD (1987) Increased seizure frequency with generic primidone. JAMA 9:1216–1217
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
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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
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DOI: https://doi.org/10.1007/s00115-010-2933-8