Long-Term Open-Label Study of Adjunctive Topiramate in Infants With Refractory Partial-Onset Seizures

Puri, Vinay; Ness, Seth; Sattaluri, Sita; Wang, Steven; Todd, Mike J.; Yuen, Eric; Eerdekens, Mariëlle; Nye, Jeffrey S.; Manitpisitkul, Prasarn; Shalayda, Kevin; Ford, Lisa

doi:10.1177/0883073811406982

Cited by 17 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patients with DS may be taking multiple concurrent ASMs and still treatment in those patients may fail to achieve adequate seizure control [15]. Topiramate, stiripentol, ethosuximide, and high-dose valproic acid-common concomitant ASMs for patients with DS-have been associated with anorexia [7,16,17].…”

Section: Discussionmentioning

confidence: 99%

Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth

Gil‐Nagel

Sullivan

Ceulemans

et al. 2021

Epilepsy & Behavior

View full text Add to dashboard Cite

Objective: Appetite disturbance and growth abnormalities are commonly reported in children with Dravet syndrome (DS). Fenfluramine (Fintepla) has demonstrated profound reduction in convulsive seizure frequency in DS and was recently approved for use in DS in the US and EU. Prior to its use in epilepsy, fenfluramine was approved to suppress appetite in obese adults. Here, we evaluated the impact of fenfluramine on weight and growth in patients with DS treated for !12 months or !24 months and compared the results with growth curves in normative reference populations and published historical controls among patients with DS. Methods: Historical control data from a recent study of 68 patients with DS show decreases in height and weight Z-scores of $0.1 standard deviation (SD) for every 12-month increase in age (Eschbach K. Seizure. 2017;52:117-22). Anthropometric data for fenfluramine were extracted from an open-label extension (OLE) study of eligible patients with DS (2-18 y/o; fenfluramine dose: 0.2-0.7 mg/kg/day). Z-score analyses were based on the Boston Children's Hospital algorithm and assessed potential impact of fenfluramine on growth at OLE baseline, at Month 12, and at Month 24. A mixed-effect model for repeated measures (MMRM) estimated changes in height and weight over time. Height and weight Z-scores were also analyzed by dose group (0.2-<0.3 mg/kg/day, 0.3-<0.5 mg/kg/day, and 0.5-0.7 mg/kg/day), averaged over time. Results: At the time of analysis, 279 patients were treated with fenfluramine for !12 months; 128 were treated for !24 months. Relative to the reference population with DS, fenfluramine treatment for !12 months or for !24 months had minimal impact on height or weight over time as assessed by Zscore analyses. No substantial dose-dependent changes from baseline were observed at Month 12 nor at Month 24. MMRM showed that patients treated with fenfluramine for !12 months (N = 262) had an estimated change in Z-score per year of À0.056 for height and À0.166 for weight. For patients with data from all three time points (baseline, 12 months, and 24 months; N = 110), estimated changes in Z-scores per year were À0.025 for height and À0.188 for weight. MMRM projections based on normative reference growth curves were comparable to growth data from historical control populations with DS. Significance/Conclusion: Long-term treatment with fenfluramine had minimal impact on the growth of patients with DS as demonstrated by differences in Z-scores for height and weight at 12 months and at

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth

Gil‐Nagel

Sullivan

Ceulemans

et al. 2021

Epilepsy & Behavior

View full text Add to dashboard Cite

show abstract

“…2 In an open-label extension study of 284 paediatric patients aged 1 to 24 months with epilepsy and TPM prescription for up to 1 year, 7% developed kidney stone or bladder stone diagnosed clinically or by sonogram. 11 Mahmoud et al 2 also reported five asymptomatic stone formers in 96 children on TPM. The median time between initiation of TPM treatment and stone detection by USG was 21.2 months.…”

mentioning

confidence: 95%

Nephrolithiasis associated with the use of topiramate in children

2017

View full text Add to dashboard Cite

“…1). The OLE safety data were reported previously as part of a combined analysis of long‐term safety (Puri et al., 2011). The study was conducted in 17 centers in five countries (U.S.A., Brazil, India, Russia, and Ukraine).…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics and safety of adjunctive topiramate in infants (1–24 months) with refractory partial‐onset seizures: A randomized, multicenter, open‐label phase 1 study

et al. 2012

Self Cite

View full text Add to dashboard Cite

SUMMARYPurpose: To characterize the pharmacokinetics of adjunctive topiramate in infants (1-24 months) with refractory partial-onset seizures (POS); also to evaluate safety and tolerability of topiramate in the dose range of 3-25 mg/kg/day. Methods: In this open-label phase 1 study, infants (N = 55) with refractory POS receiving at least one concurrent antiepileptic drug (AED) were enrolled. Infants were stratified by age and randomly assigned to one of four topiramate target dose groups (3-, 5-, 15-, or 25 mg/kg/ day). Treatment was initiated at 3 mg/kg/day with titration to the target dose by weekly dose escalation. Topiramate was administered daily in two divided doses as oral liquid (5 mg/ml for infants <9 kg or those who could not tolerate solid foods) or sprinkle capsule (25 mg) formulations. Following seven consecutive days of topiramate administration at the target dose, four blood samples were collected from each infant for pharmacokinetic assessments (predose, 1-3, 4-6, and 8-10 . Apparent steady state oral clearance (CL ss /F) remained similar across all topiramate target dose groups and was independent of creatinine clearance, age, and weight. Mean values for CL ss /F were approximately twofold greater in infants receiving concomitant enzymeinducing AEDs versus enzyme-inhibiting AEDs. Topiramate was well tolerated and safety findings were consistent with previous reports in children and adults. Most common treatment emergent adverse events ( ‡10%) were upper respiratory tract infection, fever, vomiting, somnolence, and anorexia. Significance: In infants (1-24 months), topiramate exhibited linear steady state pharmacokinetics over the dose range 3-25 mg/kg/day, and CL ss /F of topiramate was independent of dose. Moreover, the concomitant enzymeinducing AEDs doubled the clearance of topiramate. Topiramate was generally well tolerated as adjunctive therapy at doses up to 25 mg/kg/day.

show abstract

Long-Term Open-Label Study of Adjunctive Topiramate in Infants With Refractory Partial-Onset Seizures

Cited by 17 publications

References 30 publications

Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth

Treatment with fenfluramine in patients with Dravet syndrome has no long-term effects on weight and growth

Nephrolithiasis associated with the use of topiramate in children

Pharmacokinetics and safety of adjunctive topiramate in infants (1–24 months) with refractory partial‐onset seizures: A randomized, multicenter, open‐label phase 1 study

Contact Info

Product

Resources

About