Abstract
During the past few years, the use and substitution of generic antiepileptic drug products has been increasing both in the United States as well as globally. Although these less expensive products may represent an important alternative for many patients, there may be reasons for concern. Despite well-controlled regulatory studies, concerns persist regarding potential therapeutic inequivalence in some patients with epilepsy. These concerns have prompted some in the US neurology community as well as patient advocacy groups to question the current regulatory requirements for both establishing bioequivalence as well as product substitution. In addition, recent data have questioned the actual cost savings associated with generic substitution in this unique patient population. This article reviews current regulatory requirements and pharmacokinetic, biopharmaceutical, and clinical outcome issues that clinicians, pharmacists, and policymakers should consider regarding generic substitution of these complicated agents.
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References and Recommended Reading
Berg MJ: What’s the problem with generic antiepileptic drugs? A call to action. Neurology 2007, 68:1245–1246.
Liow K, Barkley G, Pollard J, et al.: Position statement on the coverage of anticonvulsant drugs for the treatment of epilepsy. Neurology 2007, 68:1249–1250.
Gidal BE, Tomson T: Debate: Substitution of generic drugs in epilepsy: Is there cause for concern? Epilepsia 2009, 49:56–62.
Bialer M: Generic products of antiepileptic drugs (AEDs): Is it an issue? Epilepsia 2007, 48:1825–1832.
Crawford P, Feely M, Guberman A, Kramer G: Are there potential problems with generic substitution of antiepileptic drugs? A review of issues. Seizure 2006, 15:165–176.
Wilner A: Physicians underestimate the frequency of generic carbamazepine substitution: results of a survey and review of the problem. Epilepsy Behav 2002, 3:522–525.
Guberman A, Corman C: Generic substitution for brand name antiepileptic drugs: a survey. Can J Neurol Sci 2000, 27:37–43.
Berg MJ: Abstract 2.105. Presented at the 60th annual meeting of the American Epilepsy Society. San Diego; December 1–5, 2006.
Haskins LS, Tomaszewski KJ, Crawford P: Patient and physician reactions to generic antiepileptic substitution in the treatment of epilepsy. Epilepsy Behav 2005, 7:98–105.
Papsdorf TB, Ablah E, Ram S, et al.: Patient perception of generic antiepileptic drugs in the Midwestern United States. Epilepsy Behav 2009, 14:150–153.
Berg MJ, Gross RA, Tomaszewski KJ, et al.: Generic substitution in the treatment of epilepsy. Case evidence of breakthrough seizures. Neurology 2008, 71:525–530.
Amidon GL, Lennernas H, Shah V, Crison J: A theoretical basis for a biopharmaceutics drug classification system; the correlation of in vitro product dissolution and in vivo bioavailability. Pharm Res 1995, 12:413–420.
Spina E: Carbamazepine: chemistry, biotransformation, and pharmacokinetics. In Antiepileptic Drugs, edn 5. Edited by Levy RH, Mattson RH, Meldrum BS, Perucca E. Philadelphia: Lippincott Williams & Wilkins; 2002:236–246.
Dickens M, Chen C: Lamotrigine: chemistry, biotransformation, and pharmacokinetics. In Antiepileptic Drugs, edn 5. Edited by Levy RH, Mattson RH, Meldrum BS, Perucca E. Philadelphia: Lippincott Williams & Wilkins; 2002:370–379.
Bialer M. Oxcarbazepine: chemistry, biotransformation, and pharmacokinetics. In Antiepileptic Drugs, edn 5. Edited by Levy RH, Mattson RH, Meldrum BS, Perucca E. Philadelphia: Lippincott Williams & Wilkins; 2002:459–465.
Meyer MC, Straugh AB: Biopharmaceutical factors in seizure control and drug toxicity. Am J Hosp Pharm 1993, 50(12 Suppl 5):S17–S22.
Tyrer J, Eadie M, Sutherland J, Hooper W: Outbreak of anticonvulsant intoxication in an Australian city. Br Med J 1970, 4:271–273.
Meyer MC, Straugh AB, Jarvi EJ, et al.: The bioinequivalence of carbamazepine tablets with a history of clinical failures. Pharm Res 1992, 12:1612–1616.
Merer MC, Straugh AB, Mhatre RM, et al.: The relative bioavailability and in vivo-in vitro correlations for four marketed carbamazepine tablets. Pharm Res 1998, 11:1787–1791.
Mayer T, May TW, Altenmuller DM, et al.: Clinical problems with generic antiepileptic drugs. Clin Invest Drug 1999, 18:17–26.
Revankar SN, Desai ND, Bhatt AD, et al.: Comparison of absorption rate and bioavailability of two brands of carbamazepine. J Assoc Physicians India 1999, 47:699–702.
Gidal BE: Drug absorption in the elderly: biopharmaceutical considerations for antiepileptic drugs. Epilepsy Res 2006, 68S:S65–S69.
Birnbaum A, Hardie NA, Leppik IE, et al.: Variability of total phenytoin serum concentrations within elderly nursing home residents. Neurology 2003, 60:555–559.
Rosenbaum DH, Rowan J, Tuchman L, French JA: Comparative bioavailability of a generic phenytoin and Dilantin. Epilepsia 1994, 335:656–600.
Burkhardt RT, Leppik IE, Blesi K, et al.: Lower phenytoin serum levels in persons switched from brand to generic phenytoin. Neurology 2004, 63:1494–1496.
Wilder BJ, Leppik I, Hietpas TJ, et al.: Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules. Neurology 2001, 57:582–589.
Zachry WM, Doan Quynhchau D, Clewell JD, Smith BJ: Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes. Epilepsia 2009, 50:493–500.
Andermann F, Duh M, Gosselin A, Paradis P: Compulsory generic switching of antiepileptic drugs: high switchback rates to branded compounds compared with other drug classes. Epilepsia 2007, 48:464–469.
LeLorier J, Duh MS, Paradis PE, et al.: Clinical consequences of generic substitution of lamotrigine for patients with epilepsy. Neurology 2008, 27:2179–2186.
Duh MS, Andermann F, Paradis PE, et al.: The consequences of generic substitution for antiepileptic drugs in a public payer setting: the case of lamotrigine. Dis Manag 2007, 10:216–225.
Lelorier J, Duh MS, Paradis P, et al.: Economic impact of generic substitution of lamotrigine: projected costs in the US using findings in a Canadian setting. Curr Med Res Opin 2008, 24:1069–1081.
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Gidal, B.E. Bioequivalence of antiepileptic drugs: How close is close enough?. Curr Neurol Neurosci Rep 9, 333–337 (2009). https://doi.org/10.1007/s11910-009-0050-5
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DOI: https://doi.org/10.1007/s11910-009-0050-5