In a mini review, author a Roy G Beran discusses what is the relevance of a narrow therapeutic index (NTI) to the treatment of epilepsy [1].
Anti-seizure medications (ASMs) control approximately two thirds of seizures in people with epilepsy (PWE) [2], confirming that ASMs still require considerable expertise [3] to manage appropriate dosing, with a stable regime, devoid of unnecessary fluctuations, especially once stability and seizure freedom has been achieved.
The narrow therapeutic index (NTI) of ASMs, is of significance when treating PWE, who comprise approximately 2% of the population [4]. Some ASMs have more than 10 generic alternatives and the problem arises when substituting one generic formulation for another. As already demonstrated, this may either double or halve the available active ingredients [5] with potentially serious consequences for vulnerable PWE. A way to protect, against such generic substitution, is to prescribe using the ‘trade’ name of the ASM even if prescribing a generic alternative [6]. Use of the trade name is still allowed in Australia, even when using electronic prescriptions, as long as the generic constituents are also named within the prescription [7, 8].
Australian pharmacists often advocate generic substitution because of financial gain, rather than specific consideration of the patient’s needs [9]. The Australian Pharmaceutic Benefits Scheme has encouraged generic substitution of originator medicines [10] and, from December 1994, pharmacists had the option of generic substitution [11], raising considerable concern within the Australian Medical Association [11]. Then in 2017, the prescribing software for doctors was changed to make prescribing by active ingredient the default and effectively make generics prescribing mandatory [12]. Treating physicians retain the option to prohibit brand-name substitution when writing a prescription, but respect for this authority is far from universal [13], with some pharmacists totally ignoring this directive from the treating/prescribing doctor [13]. This has the potential to adversely affect PWE because of significant alterations in the bioavailability.
Often such criticisms are viewed as being hypothetical but that is far from the facts, as one case clearly shows. A patient admitted to hospital was automatically given the generic alternative of her usual ASM, as was included in the hospital formulary, and without her knowledge or consent. This resulted in halving the therapeutic blood levels of her ASM and causing her to experience break through seizures, after years of stable seizure control [14]. The patient was neither driving nor handling machinery, at the time of the seizure, but that was a case of good luck, rather than good management. Had she been injured in any way, as a result of the generic substitution, without advice nor consent, the hospital may well have been the subject of litigation due to negligence and failure to provide adequate warning of the risks of substitution [6].
The author therefore concludes that generic substitution requires advice and the patient’s consent. Prescribing, using trade names, may avoid brand-name substitution.
Conflict of interest
The author of the research paper [1] declared that there was no conflict of interest.
Abstracted by Professor Roy G Beran, Neurology Department, Liverpool Hospital, Liverpool, Australia.
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References
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12. GaBI Online - Generics and Biosimilars Initiative. Concerns over change to generics prescribing in Australia [www.gabionline.net]. Mol, Belgium: ProPharma Communications International; [cited 2022 Jul 1]. Available from: www.gabionline.net/es/genericos/general/Concerns-over-change-to-generics-prescribing-in-Australia
13. Beran RG. Generic substitution in contravention of doctor’s prescriptions. Intern Med J. 2015;45(10):1093.
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