Antiepileptic drug treatment in children

Hadjiloizou, Stavros; Bourgeois, Blaise F. D.

doi:10.1586/14737175.7.2.179

Cited by 34 publications

(30 citation statements)

References 106 publications

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“…VB (4-amino-5-hexenoic acid) is a GABA-aminotransferase inhibitor to antagonize the GABA degradation in synapses [191]. VB is rapidly absorbed in small intestines and widely distributed throughout the body [192].…”

Section: New Generation Aedsmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

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Section: New Generation Aedsmentioning

confidence: 99%

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Fan

Lee

Chang

et al. 2016

IJMS

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“…Epilepsy affects about 4 to 6 out of 1000 children below the age of 20 years, and the overall annual incidence rates of epilepsy for all seizure types range between 45 and 86 out of 100,000 children. Despite the availability of new antiepileptic drugs (AEDs), more than 25% of paediatric patients have inadequate seizure control on currently available AEDs, or experience significant adverse drug effects [2]. There remains a need for potent AEDs with a positive benefit-risk profile in this population.…”

Section: Introductionmentioning

confidence: 99%

Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years

Schoemaker¹,

Wade²,

Stockis

2017

Eur J Clin Pharmacol

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PurposeThe aims of the study were to develop a population pharmacokinetic model of orally administered brivaracetam in paediatric patients and to provide dosing suggestions.MethodsAnalysis included 600 brivaracetam plasma concentrations from a phase 2a study (NCT00422422; N01263) in 96 paediatric patients with epilepsy aged 1 month to 16 years, taking one to three concomitant antiepileptic drugs (AEDs). Pharmacokinetic analysis was performed using non-linear mixed effects modelling, and a stepwise covariate search was used to determine factors influencing brivaracetam clearance. Simulations were performed to investigate dosing regimens.ResultsThe final model consisted of first-order absorption, single compartment distribution and first-order elimination components with allometric scaling of clearance and volume using lean body weight and fixed allometric exponents. Co-administration with phenobarbital or carbamazepine was associated with a 29% (95%CI 17%/39%) and 32% (22%/42%) decrease in exposure, respectively. Co-administration with valproate was associated with an 11% (1%/23%) increase in exposure. Simulations demonstrated that the majority of children were predicted to have an exposure similar to that in adults, using an age-independent dosing regimen of 2.0 mg/kg bid with a maximum of 100 mg bid for body weight >50 kg.ConclusionsA paediatric dose adaptation of 2.0 mg/kg twice daily with a maximum of 100 mg twice daily for body weight >50 kg is predicted to ensure steady-state plasma concentrations in the same range as in adult patients receiving 100 mg twice daily (highest recommended dose). Data suggest no need to change brivaracetam dosing when used concomitantly with carbamazepine, phenobarbital or valproate.Electronic supplementary materialThe online version of this article (doi:10.1007/s00228-017-2230-6) contains supplementary material, which is available to authorized users.

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“…A significant amount of research exists detailing the side effect profiles of various AED drugs used in the treatment of seizure disorders. Several studies have explored patient tolerance and side effect comparisons of first-generation versus second-generation AEDs [10, 12–17]. While the second-generation AEDs have shown greater tolerability and lower side effect profiles, there is an ongoing debate about the cost effectiveness of these newer AEDs [12].…”

Section: Introductionmentioning

confidence: 99%

Identification and Prevention of Antiepileptic Drug Noncompliance: The Collaborative Use of State-Supplied Pharmaceutical Data

et al. 2014

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Background. Antiepileptic drugs (AEDs) noncompliance is associated with increased risk of seizures and morbidity in seizure disorder patients. Objective. To identify risk factors that correlated to higher levels of morbidity, measured by emergency room (ER) utilization by seizure disorder members taking AED. Methods. Patients with primary or secondary diagnosis of seizures, convulsions, and/or epilepsy and prescribed AEDs during an 11-month period were included in the study. Variables were analyzed using multivariate statistical analysis including logistic regression. Results. The study identified 201 members. No statistical significance (NS) between age, gender, number of tablets, type of drug, or other risk factors was associated with increased mortality. Statistical significance resulted with medication compliance review of 0–14 days, 15–60 days, and 61+ days between refills. 68% of patients with ER visit had noncompliance refill between 0 and 14 days compared to 52% of patients in non-ER group (P = 0.04). Contrastingly, 15% of ER group had refills within 15–60 days compared with 33% of non-ER group (P = 0.01). There was NS difference between two groups when noncompliance was greater than 60 days (P = 0.66). Conclusions. The study suggests that careful monitoring of pharmaceutical refill information could be used to identify AED noncompliance in epileptic patients.

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Antiepileptic drug treatment in children

Cited by 34 publications

References 106 publications

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism

Brivaracetam population pharmacokinetics in children with epilepsy aged 1 month to 16 years

Identification and Prevention of Antiepileptic Drug Noncompliance: The Collaborative Use of State-Supplied Pharmaceutical Data

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