Intrapatient variation in antiepileptic drug plasma concentration after generic substitution vs stable brand-name drug regimens

Contin, Manuela; Alberghini, Lucia; Candela, Carmina; Benini, Giulia; Riva, R.

doi:10.1016/j.eplepsyres.2016.02.012

Cited by 28 publications

(21 citation statements)

References 14 publications

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“…Secondly, blood samples for LEV concentration measurements were not collected and scaled‐average bioequivalence was not evaluated , limiting the possibility of comparing drug bioavailability. Furthermore, clinical efficacy is not necessarily strictly correlated to blood plasma levels as it is known that intrapatient blood concentration oscillations occur over time . A further limitation of our study was the assessment of adherence in our outpatients using self‐report measures (face‐to‐face), although indirect instruments (pill counts, medication event‐monitoring systems and self‐reporting questionnaire) have been developed in the last few years .…”

Section: Discussionmentioning

confidence: 99%

Brand‐to‐generic levetiracetam switching: a 4‐year prospective observational real‐life study

Trimboli

Russo

Mumoli

et al. 2018

Euro J of Neurology

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Section: Discussionmentioning

confidence: 99%

Brand‐to‐generic levetiracetam switching: a 4‐year prospective observational real‐life study

Trimboli

Russo

Mumoli

et al. 2018

Euro J of Neurology

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“…A significant inter-day variability in intra-patient plasma concentrations was noted, even in patients stabilized with the same brand name product over time. 52 …”

Section: Main Textmentioning

confidence: 99%

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

Ilan

2020

Molecular Therapy - Methods & Clinical Development

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Chronic administration of drugs leads to the activation of compensatory mechanisms that may inhibit some of their activity and induce unwanted toxicity. These mechanisms are an obstacle for maintaining a sustainable effect for many chronic medications. Pathways that adapt to the burden induced by chronic drugs, whether or not related to the underlying disease, can lead to a partial or complete loss of effect. Variability characterizes many biological systems and manifests itself as large intra- and inter-individual differences in the response to drugs. Circadian rhythm-based chronotherapy is further associated with variability in responses noted among patients. This paper reviews current knowledge regarding the loss of effect of chronic medications and the range of variabilities that have been described in responses and loss of responses. Establishment of a personalized platform for overcoming these prohibitive mechanisms is presented as a model for ensuring long-term sustained medication effects. This novel platform implements personalized variability signatures and individualized circadian rhythms for preventing and opposing the prohibitive effect of the compensatory mechanisms induced by chronic drug administration.

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“…A retrospective analysis of therapeutic drug monitoring data from 2009 to 2014 analyzed the proportion of patients switched from branded to generic formulations that showed a >20% change in AED plasma concentration, compared to the proportion of patients showing a similar change in AED plasma concentrations on stable branded formulations . The proportion of patients with a change >20% in AED plasma concentrations was similar for lamotrigine (22% switched from brand to generic vs 33% maintained on brand) and levetiracetam (44% vs 38%), whereas it was higher in the group maintained on brand for topiramate (6% vs 41%, P < .01).…”

Section: Intra‐individual Variability Of Aed Serum Concentrationsmentioning

confidence: 99%

Generic antiepileptic drugs—Safe or harmful in patients with epilepsy?

Holtkamp

Theodore

2018

Epilepsia

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Summary Generic antiepileptic drugs (AED) are significantly cheaper than brand name drugs, and may reduce overall health care expenditures. Regulatory bodies in Europe and North America require bioequivalence between generic and innovator drugs with regard to area under the plasma concentration–time curve (AUC) and peak plasma concentration (Cmax); strict cutoff values have been defined. The main issue is if bioequivalence ensures therapeutic equivalence. Are switches from brand to generic, or between generic AEDs entirely safe or potentially harmful in patients with epilepsy? We summarized and evaluated the available evidence from bioequivalence, health care utilization, and clinical studies on safety of generic AEDs. In most cases, variations in AUC and Cmax were negligible when comparing innovator and generic AEDs. Due to interindividual pharmacokinetic and pharmacodynamic variability, measured differences between innovator and generic drugs may be the same as differences between different lots of the same brand. Studies from several countries based on insurance data have reported an increase in health care usage after switch from brand to generic AEDs; switchback rates are significantly higher for AEDs compared to other compounds. Patients may be confused, and nonadherence may increase, when AEDs are switched between manufacturers, perhaps due to changes in medication shape and color. But clinical studies do not report changes in seizure frequency and tolerability attributable to generics. Sufficient evidence indicates that most generics are bioequivalent to innovator AEDs; they do not pose a relevant risk for patients with epilepsy. However, some patients are reluctant towards variations in color and shape of their AEDs which may result in nonadherence. We recommend administering generics when a new AED is initiated. Switches from brand to generic AEDs for cost reduction and between generics, which is rarely required, generally seem to be safe, but should be accompanied by thorough counseling of patients on low risks.

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Intrapatient variation in antiepileptic drug plasma concentration after generic substitution vs stable brand-name drug regimens

Cited by 28 publications

References 14 publications

Brand‐to‐generic levetiracetam switching: a 4‐year prospective observational real‐life study

Brand‐to‐generic levetiracetam switching: a 4‐year prospective observational real‐life study

Overcoming Compensatory Mechanisms toward Chronic Drug Administration to Ensure Long-Term, Sustainable Beneficial Effects

Generic antiepileptic drugs—Safe or harmful in patients with epilepsy?

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