Evaluation of Safety in Exceeding Maximum Adult Doses of Commonly Used Second-Generation Antiepileptic Drugs in Pediatric Patients

Messinger, Mindl; Misra, Sunita N.; Clark, Gary D.; DiCarlo, Shannon

doi:10.5863/1551-6776-22.4.256

Cited by 2 publications

(1 citation statement)

References 14 publications

(13 reference statements)

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“…In the setting of partial adherence, this may result in supratherapeutic doses without elevated serum concentrations or signs of medication side effects. This is verified in the study by Messinger et al 1 as none of the patients taking supratherapeutic doses of lamotrigine, zonisamide, topiramate, oxcarbazepine, or levetiracetam (see Messinger et al 1 Table 2) had median serum drug concentrations that exceeded the therapeutic range (and for the first 3 medications no patient had a single value exceeding the therapeutic range). Additionally, even with supratherapeutic doses for lamotrigine, zonisamide, and topiramate, median serum concentrations were only mid-range or lower.…”

Section: Lessonmentioning

confidence: 68%

Safety of Supratherapeutic Doses of Newer Antiepileptic Drugs in Children: What Have We Really Learned?

Wheless¹

2017

The Journal of Pediatric Pharmacology and Therapeutics

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Section: Lessonmentioning

confidence: 68%

Safety of Supratherapeutic Doses of Newer Antiepileptic Drugs in Children: What Have We Really Learned?

Wheless¹

2017

The Journal of Pediatric Pharmacology and Therapeutics

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A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics: Role of Extrapolation

et al. 2018

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Most antiepileptic drugs (AEDs) receive regulatory approval for children years after the drug is available in adults, encouraging off-label use of the drug in children and hindering attempts to obtain quality pediatric data in controlled trials. Extrapolating adult efficacy data to pediatrics can reduce the time between approval in adults and that in children. To extrapolate efficacy from adults to children, several assumptions must be supported, such as (1) a similar disease progression and response to interventions in adults and children, and (2) similar exposure response in adults and children. The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) addressed these assumptions in focal-onset seizures (FOS), the most common seizure type in both adults and children. PEACE reviewed the biological and clinical evidence that supported the assumptions that children with FOS have a similar disease progression and response to intervention as adults with FOS. After age 2 years, the pathophysiological underpinnings of FOS and the biological milieu in which seizures are initiated and propagated in children, seizure semiology, electroencephalographic features, etiology and AED response to FOS in children are similar to those in adults with FOS. PEACE concluded that extrapolation of efficacy data in adults to pediatrics in FOS is supported by strong scientific and clinical evidence. However, safety and pharmacokinetic (PK) data cannot be extrapolated from adults to children. Based on extrapolation, eslicarbazepine is now approved for children with FOS, down to age 4 years. Perampanel, lacosamide and brivaracetam are now undergoing PK and safety studies for the purposes of extrapolation down to age 2 or 4 years. When done in conjunction with PK and safety investigations in children, extrapolation of adult data from adults to children can reduce the time delay between approval of effective and safe AEDs in adults and approval in children.

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Evaluation of Safety in Exceeding Maximum Adult Doses of Commonly Used Second-Generation Antiepileptic Drugs in Pediatric Patients

Abstract: It appears safe to use doses exceeding the maximum approved dose of the evaluated AEDs in pediatric patients, with appropriate counseling and monitoring for adverse effects.

Cited by 2 publications

References 14 publications

Safety of Supratherapeutic Doses of Newer Antiepileptic Drugs in Children: What Have We Really Learned?

Safety of Supratherapeutic Doses of Newer Antiepileptic Drugs in Children: What Have We Really Learned?

A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics: Role of Extrapolation

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