In 2009 the first case-control analysis to determine the odds of AED substitution among patients requiring emergency care was published in the journal Epilepsia (Zachry, et al). Using the Ingenix LabRX data base, the study reported that patients who had an epileptic event requiring emergency care, who had not required care for at least six months, had 81% greater odds of having an AED formulation switch.
The results of the Zachry study have been replicated using a different data base (PharMetrics) and an even larger control group. Published in the July 2009 issue of the journal Pharmacotherapy, Rascati and colleagues conclude: “Patients who had an epileptic event requiring acute care were about 80% more likely than matched controls without an acute event to have recently had an antiepileptic drug substitution. Replication of a previously published case-control analysis revealed a similar association between substitution involving A-rated antiepileptic drugs and subsequent epileptic events requiring acute care, thereby lending credibility to the findings.”
Most recently, in an article titled “Antiepileptic drugs: the drawbacks of generic substitution,” the journal The Lancet Neurology stated that “until firm evidence supporting the safety of generic switching becomes available, we should err on the side of caution and ensure that AEDs are excluded from any sweeping policies that promote automatic generic substitution.”
In addition, the journal Neurology published a study by Labiner, et al., which found that with five common AEDs in the U.S., generic substitution was associated with significantly greater use of medical resources and risk of epilepsy-related medical events, compared to brand use.
Links to these articles, and others, appear below.
- Antiepileptic drugs: the drawbacks of generic substitution. The Lancet Neurology, Vol. 9; p. 227 (2010)
Andermann, F., et al, Compulsory generic switching of antiepileptic drugs: Higher switchback rates to branded compounds compared with other drug classes. Epilepsia, 48(3); 464-469 (2007).
- Berg, M.J., et al, Generic substitution in the treatment of epilepsy: Case evidence of breakthrough seizures. Neurology 71; 535-530 (2008).
- Berg, M.J., et al, Generic substitution in the treatment of epilepsy: Patient and physician perceptions. Epilepsy & Behavior 13 693–699 (2008).
- Burkhardt, R.T., PharmD, et al., Lower phenytoin serum levels in persons switched from brand to generic phenytoin. Neurology 63 (2004).
- Duh, M.S, et al, The risks and costs of multiple-generic substitution of topiramate. Neurology 72; 2122-2129 (2009).
- Freely, M., et al, Risk management in epilepsy: generic substitution and continuity of supply. European Journal of Hospital Pharmacy Science Vol. 11, Issue 4; 83 – 87 (2005).
- Hansen R.N., Campbell J.D., Sullivan S.D., Association between antiepileptic drug switching and epilepsy-related events. (2009) Epilepsy and Behavior,15 (4); 481-485 (2009).
- Helmers, Sandra, et al., Economic burden associated with the use of generic antiepileptic drugs in the United States. Epilepsy & Behavior 18; 437-444 (2010).
- Labiner, D.M., et al., Generic antiepileptic drugs and associated medical resource utilization in the United States. Neurology 74: 1566-1574 (2010).
Mayer, T., et al, Clinical Problems with Generic Antiepileptic Drugs: Comparison of Sustained-Release Formulations of Carbamazepine. Clinical Drug Investigation, Volume 18,Number 1, 17-26(10) (1999).
- McAuley, J.W., et al, An assessment of patient and pharmacist knowledge of and attitudes toward reporting adverse drug events due to formulation switching in patients with epilepsy. Epilepsy & Behavior 14; 113-117 (2009).
- Nielsen, K.A., et al, Comparative daily profiles with different preparations of lamotrigine: A pilot investigation. Epilepsy & Behavior 13; 127-140 (2008).
- Rascati, K.L., Ph.D.,et al, Effects of Antiepileptic Drug Substitutions on Epileptic Events Requiring Acute Care. Pharmacotherapy, Volume 29, Number 7 (2009).
- Steinhoff, B.J., et al., Substitution of Anticonvulsant Drugs. Therapeutics and Clinical Risk Management 5: 449-457 (2009).
- Zachry, W.M. III., et al., Case-control analysis of ambulance, emergency room, or inpatient hospital events for epilepsy and antiepileptic drug formulation changes. Epilepsia, 50 (3); 493-500 (2009).