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| 2. |
- Andermann, E., et al.
(author)
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Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (>= 60 years) and younger (18-59 years) adults
- 2021
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In: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 169
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Journal article (peer-reviewed)abstract
- Objective: To investigate the safety and tolerability of eslicarbazepine acetate (ESL), a once-daily oral anti-seizure drug (ASD), in older and younger adult patient populations. Methods: Two post-hoc pooled data analyses were performed: one from three Phase III studies in patients with focal (partial-onset) seizures who were taking 1-3 concomitant ASDs; the other from five Phase II studies in patients from non-epilepsy populations not taking other ASDs chronically and/or at a clinically-effective anti-seizure dose. The frequencies of treatment-emergent adverse events (TEAEs) were calculated for the older (>= 60 years) and younger (18-59 years) adults separately. Results: In the focal seizures study pool, 4.1 % of patients (58/1431) were aged >= 60 years. The overall frequency of TEAEs was 77.5 % in older ESL-treated patients and 72.6 % in younger ESL-treated patients (p = 0.495). For patients who received placebo, the overall frequency of TEAEs was 50.0 % in the older adults and 57.5 % in the younger adults (p = 0.531). The overall placebo-adjusted frequency of TEAEs was 27.5 % in older adults and 15.1 % in younger adults. The placebo-adjusted frequencies of the TEAEs dizziness, somnolence, headache, nausea, diplopia, blurred vision, and ataxia were >= 5 % higher, and frequencies of vomiting and vertigo were >= 2 % higher in older than younger adults. The overall frequency of TEAEs leading to discontinuation was 15.0 % in older ESL-treated patients and 17.6 % in younger ESL-treated patients (p = 0.647); the frequency increased with increasing ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 5.6 % in older adults and 6.6 % in younger adults (p = 0.847). In the non-epilepsy study pool, 30.2 % of patients (515/1705) were aged >= 60 years. The overall frequency of TEAEs was 56.9 % in older ESL-treated patients and 58.8 % in younger ESL-treated patients. The placebo-adjusted frequencies were 14.9 % in older and 15.1 % in younger ESL-treated patients. The placebo-adjusted frequencies of the TEAEs nausea, vomiting, fatigue, and vertigo were >= 2 % higher in older adults, whereas somnolence was >= 2 % higher in younger adults. The overall frequency of TEAEs leading to discontinuation was 18.3 % in older ESL-treated patients and 12.1 % in younger ESL-treated patients (p = 0.003); frequencies were not related to ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 8.0 % in older adults and 5.6 % in younger adults (p = 0.407). Conclusion: Analyses of adverse event data support the safety and tolerability of ESL in adults aged >= 60 years. In the limited number of older patients with focal seizures taking ESL plus concomitant ASDs (n = 40), the frequency of TEAEs was generally higher than in younger adults. However, in the non-epilepsy patient group (in which the number of older patients was ten times larger; 427 patients taking ESL without concomitant ASDs), no marked age-related TEAE differences were observed, suggesting that increased ASD load associated with adjunctive therapy may complicate treatment selection in older patients, due to risk of increased adverse events. As is common practice for all ASDs, balancing clinical response and tolerability is needed in this vulnerable group of patients.
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| 3. |
- Andermann, E., et al.
(author)
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Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures
- 2018
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In: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 82, s. 119-127
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. Methods: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400 mg (studies 301 and 302 only), 800 mg, or 1200 mg once daily (QD) for 14 weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. Results: The analysis population included 1447 patients (ESL, n = 1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p = 0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p = 0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p = 0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200 mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs were (0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL. and 0.7% and 0.5% taking placebo, respectively. Conclusions: In phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. The incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo. © 2017
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| 4. |
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| 5. |
- Bauer, J, et al.
(author)
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Levetiracetam: a long-term follow-up study of efficacy and safety.
- 2006
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In: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 114:3, s. 169-76
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the efficacy and safety of long-term add-on treatment with levetiracetam 1,000-4,000 mg/day. PATIENTS AND METHODS: In this multicenter, open-label follow-up study, 505 patients, from 10 European countries, who had benefited from previous add-on treatment with levetiracetam in a clinical trial or compassionate-use program were enrolled; 274 (54.3%) stayed to the end. Most then continued levetiracetam by prescription or in a named patient program, where it was not yet commercially available. Mean treatment duration was 1,045 days (range: 24 days to >7 years). Median daily dosage was 3,000 mg/day (range: 250-6,000 mg/day), with 250 (49.5%) patients receiving levetiracetam for >3 years. RESULTS: Median total and partial seizure frequency per week over the evaluation period were 0.8 and 0.7; seizure frequency per week was generally stable over time and remained low. There was a probability of 6.6% of remaining seizure-free for the first 3 years, and of 18.9% of having a seizure-free period of at least 3 years at any time. Most adverse events were mild or moderate and unrelated to study drug. Levetiracetam was well tolerated, and provided stable seizure control during long-term treatment.
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| 6. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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A Phase II Randomized Trial to Explore the Potential for Pharmacokinetic Drug-Drug Interactions with Stiripentol or Valproate when Combined with Cannabidiol in Patients with Epilepsy
- 2020
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In: Cns Drugs. - : Springer Science and Business Media LLC. - 1172-7047 .- 1179-1934. ; 34:6, s. 661-672
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Journal article (peer-reviewed)abstract
- Background In recent randomized, placebo-controlled, phase III trials, highly purified cannabidiol demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome. It is anticipated that antiepileptic drugs such as stiripentol and valproate will be administered concomitantly with cannabidiol. Objectives This trial evaluated the effect of cannabidiol on steady-state pharmacokinetics of stiripentol or valproate in patients with epilepsy, and the safety and tolerability of cannabidiol. Methods This phase II, two-arm, parallel-group, double-blind, randomized, placebo-controlled trial recruited male and female patients with epilepsy aged 16-55 years. Patients receiving a stable dose of stiripentol or valproate were randomized 4:1 to receive concomitant double-blind cannabidiol or placebo. Patients received plant-derived, highly purified cannabidiol medicine (Epidiolex(R) in the USA; Epidyolex(R) in the EU; 100 mg/mL oral solution) at a dose of 20 mg/kg/day from day 12 to 26, following a 10-day dose-escalation period. Blood samples for pharmacokinetic evaluations were collected on days 1 and 26 before stiripentol/valproate dosing and up to 12 h postdose. Treatment-emergent adverse events (AEs) were recorded. Results In total, 35 patients were recruited to the stiripentol arm (n = 14) or the valproate arm (n = 21). Both the safety and the pharmacokinetic populations of the stiripentol arm comprised 14 patients (2 placebo; 12 cannabidiol). The safety population of the valproate arm comprised 20 patients (4 placebo; 16 cannabidiol; one withdrew before receiving treatment); the pharmacokinetic population comprised 15 patients (3 placebo; 12 cannabidiol). Concomitant cannabidiol led to a small increase in stiripentol exposure (17% increase in maximum observed plasma concentration [C-max]; 30% increase in area under the concentration-time curve over the dosing interval [AUC(tau)]). Concomitant cannabidiol also had little effect on valproate exposure (13% decrease in C-max; 17% decrease in AUC(tau)) or its metabolite, 2-propyl-4-pentenoic acid (4-ene-VPA) (23% decrease in C-max; 30% decrease in AUC(tau)). All changes in exposure are expressed as the dose-normalized geometric mean (CV%) day 26 to day 1 ratio. The most common AE was diarrhea; most AEs were mild. Two patients discontinued cannabidiol because of serious AEs (rash [n = 1] in the stiripentol arm; hypertransaminasemia [n = 1] in the valproate arm). A separate in vitro study investigated the bidirectional effect of cannabidiol, or its metabolite 7-carboxy-cannabidiol, on valproate plasma protein binding; no change in plasma protein binding was observed for either compound. Conclusions The clinical relevance of the increase in stiripentol exposure is unknown; patients receiving cannabidiol and stiripentol concomitantly should be monitored for adverse reactions as individual patient responses may vary. Coadministration of cannabidiol did not affect the pharmacokinetics of valproate or its metabolite, 4-ene-VPA, in adult patients with epilepsy. Safety results were consistent with the known safety profile of cannabidiol at a dose of 20 mg/kg/day. Clinicaltrials.gov: NCT02607891.
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| 7. |
- Ben-Menachem, Elinor, 1945
(author)
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AAN/AES guidelines on use of new AEDS.
- 2005
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In: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:1, s. 30-2
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Journal article (peer-reviewed)
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| 8. |
- Ben-Menachem, Elinor, 1945
(author)
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Data from regulatory studies: What do they tell? What don't they tell?
- 2005
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In: Acta neurologica Scandinavica. Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314 .- 1600-0404. ; 181, s. 21-5
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Journal article (peer-reviewed)abstract
- Phase III studies of antiepileptic drugs (AEDs) are specifically designed to satisfy strict regulatory criteria. As they are conducted in protocol-restricted patient populations over short treatment periods and employ fixed study designs and dosing schedules, they are not fully representative of 'real-life' clinical practice. Therefore, in order to provide an overall assessment of clinical performance, regulatory studies must be backed up by post-marketing clinical experience. Phase IV studies provide information on a drug's performance in a setting more closely representing real clinical practice, with broader patient populations and a more flexible approach to individual treatment. Prospective long-term studies allow the determination of efficacy and safety (and cost-effectiveness) over extended treatment periods; these studies and audit data provide a means of assessing idiosyncratic side effects, unusual interactions and the effects of an AED in rare patient groups. By complementing regulatory evidence with real-life clinical experience, a comprehensive assessment of the risks and benefits of an AED can be made.
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| 9. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies
- 2016
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In: Neurology. - 0028-3878. ; 87:3, s. 314-323
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Journal article (peer-reviewed)abstract
- Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16-80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8 -week baseline and a 12 -week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n = 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%-29.6%) for 50 mg/d (p = 0.0015), 24.4% (16.8%-31.2%) for 100 mg/d (p < 0.00001), and 24.0% (15.3%-31.8%) for 200 mg/d (p < 0.00001). The >50% responder rate was 34.2% (50 mg/d, p 0.0015), 39.5% (100 mg/d, p < 0.00001), and 37.8% (200 mg/d, p = 0.00003) vs 20.3% for placebo (p < 0.01). Across the safety population groups (n = 1,262), 90.0% to 93.9% completed the studies. Treatment -emergent adverse events (TEAEs) were reported by 68.0% BRV overall (n 803) and 62.1% placebo (n = 459). Serious TEAEs were reported by 3.0% (BRV) and 2.8% (placebo); 3 patients receiving BRV and one patient receiving placebo died. TEAEs in >5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS.
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| 10. |
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| 11. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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Epilepsi
- 2011
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In: Läkemedelsboken 2011-2012. - Uppsala. : Läkemedelsverket. - 9789197960502 ; , s. 965-76
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Book chapter (peer-reviewed)
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| 12. |
- Ben-Menachem, Elinor, 1945
(author)
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Epilepsy as a warning sign for stroke.
- 2005
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In: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:1, s. 42-3
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Journal article (peer-reviewed)
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| 13. |
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| 14. |
- Ben-Menachem, Elinor, 1945
(author)
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Eslicarbazepine acetate: a well-kept secret?
- 2010
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In: Epilepsy currents. - : SAGE Publications. - 1535-7511 .- 1535-7597. ; 10:1, s. 7-8
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Journal article (peer-reviewed)abstract
- PURPOSE: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ≥4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1–2 antiepileptic drugs (AEDs). METHODS: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n= 102) or once-daily ESL 400 mg (n= 100), 800 mg (n= 98), or 1,200 mg (n= 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). RESULTS: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p= 0.0003) and 800-mg (p= 0.0028) groups [analysis of covariance (ANCOVA) of log-transformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56–62% of patients), lamotrigine (25–27%), and valproic acid (22–28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. DISCUSSION: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.
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| 15. |
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| 16. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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Guidelines--are they useful?
- 2006
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In: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 47:Suppl 1, s. 62-4
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Journal article (peer-reviewed)abstract
- Antiepileptic drug (AED) guidelines are developed to improve medical decision making, to provide guidance and recommendation for patient management, to develop standards to judge or assess clinical practice, and to keep the cost-benefit ratio at an acceptable level. These guidelines are derived from evidence-based medicine (EBM), a four-tiered grading system that is used to analyze clinical trials and published experiments independent of clinical bias and experience. Although guidelines may not answer all questions it is critical that clinicians using them consider the available evidence, as well as the quality of the evidence, when incorporating the information in their decision making.
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| 17. |
- Ben-Menachem, Elinor, 1945
(author)
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Infantile spasms and epilepsy currents.
- 2005
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In: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 5:4, s. 157-8
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Journal article (peer-reviewed)abstract
- The United Kingdom Infantile Spasms Study Comparing Vigabatrin with Prednisolone or Tetracosactide at 14 Days: A Multicentre, Randomised Controlled Trial Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, O'Callaghan FJ, Verity CM, Osborne JP Lancet 2004;364:1773–1778 Infantile spasms, a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms. Methods The United Kingdom Infantile Spasms Study assessed these treatments in a multicenter, randomized controlled trial in 150 hospitals in the United Kingdom. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin, 100 mg/kg/day; oral prednisolone, 40 mg/day; or intramuscular tetracosactide depot, 0.5 mg (40 IU) on alternate days. Analysis was by intention to treat. Results Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin ( n = 52) or hormonal treatments (prednisolone, n = 30; tetracosactide, n = 25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were 40 (73%) of 55 infants assigned hormonal treatments (prednisolone, 21 of 30 [70%]; tetracosactide, 19 of 25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference, 19%; 95% CI, 1%–36%, p = 0.043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants receiving hormonal treatments and 28 (54%) of 52 infants receiving vigabatrin. No deaths were recorded. Conclusions Cessation of spasms was more likely in infants given hormonal treatments than in those given vigabatrin. Adverse events were common with both treatments.
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| 18. |
- Ben-Menachem, Elinor, 1945
(author)
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Introduction
- 2013
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In: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 127, s. 1-2
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Journal article (other academic/artistic)
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| 19. |
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| 20. |
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| 21. |
- Ben-Menachem, Elinor, 1945
(author)
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Is prolactin a clinically useful measure of epilepsy?
- 2006
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In: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 6:3, s. 78-9
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Journal article (peer-reviewed)abstract
- Use of Serum Prolactin in Diagnosing Epileptic Seizures: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Chen DK, So YT, Fisher RS Neurology 2005;65(5):668–675 (Review) The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis. Methods The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate. Results Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic–clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic–clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test–induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures. Recommendations Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic–clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).
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| 22. |
- Ben-Menachem, Elinor, 1945
(author)
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Is topiramate tops?
- 2008
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In: Epilepsy currents / American Epilepsy Society. - : SAGE Publications. - 1535-7597. ; 8:3, s. 60-1
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Journal article (peer-reviewed)abstract
- TOPIRAMATE MONOTHERAPY IN NEWLY DIAGNOSED EPILEPSY IN CHILDREN AND ADOLESCENTS: Glauser TA, Dlugos DJ, Dodson WE, Grinspan A, Wang S, Wu SC EPMN-106/INT-28 Investigators. J Child Neurol2007226:693-69917641254 A double-blind, dose-controlled study evaluated topiramate as monotherapy in 470 patients with newly diagnosed (3 months) epilepsy or epilepsy relapse in the absence of therapy. In addition to having at least 2 lifetime-unprovoked seizures, patients had 1 or 2 partial-onset seizures or generalized-onset tonic-clonic seizures during a 3-month retrospective baseline. The trial included a large cohort (N = 151, 32%) of children and adolescents 6 to 15 years of age. Eligible patients were randomized to treatment groups in which topiramate was titrated to target maintenance dosages of either 400 mg/day (n = 77) or 50 mg/day (n = 74). Patients were followed for at least 6 months. Based on Kaplan-Meier analyses, the primary efficacy endpoint of time to first seizure favored the higher topiramate dose in both the overall population and the cohort of children/adolescents. The probability that children/adolescents remaining in the study were seizure free at 6 months was 78% in the 50-mg target dose group and 90% with the higher dose. At 12 months, the probability of being seizure free was 62% and 85%, respectively. The incidence of treatment-limiting adverse events was 4% in the 50-mg target dose group and 14% in the group assigned to 400 mg as a target dose. The most common adverse events, excluding typical childhood illnesses, were headache, appetite decrease, weight loss, somnolence, dizziness, concentration/attention difficulty, and paresthesia. As shown in this subset analysis, topiramate is effective and well tolerated as monotherapy in children and adolescents.
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| 23. |
- Ben-Menachem, Elinor, 1945
(author)
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Lacosamide: an investigational drug for adjunctive treatment of partial-onset seizures.
- 2008
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In: Drugs of today (Barcelona, Spain : 1998). - : Clarivate Analytics (US). - 1699-3993. ; 44:1, s. 35-40
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Journal article (peer-reviewed)abstract
- Lacosamide, (R)-2-acetamido-N-benzyl-3-meth- oxypropionamide, is a new chemical entity specifically synthesized as an anticonvulsive drug candidate, which appears to have a novel dual mode of action. Its pharmacokinetic characteristics have been studied in young and elderly healthy adults, as well as in adults with epilepsy or diabetic neuropathic pain. After oral administration, lacosamide is rapidly and completely absorbed. An elimination half-life of 13 hours allows for twice-daily dosing. Lacosamide has a low potential for drug-drug interactions. Both oral and intravenous formulations of lacosamide are being developed. In completed placebo-controlled clinical trials, lacosamide has demonstrated efficacy as adjunctive therapy for reduction of seizure frequency in patients with uncontrolled partial-onset seizures, and has been generally well tolerated. For patients treated with lacosamide, the most frequently reported adverse events in placebo-controlled trials include dizziness, headache, nausea and diplopia. When used as short-term replacement for oral lacosamide, intravenous lacosamide has a comparable safety profile to oral lacosamide. Results from clinical trials to date suggest that lacosamide may be a useful pharmacological treatment option for patients with partial-onset seizures.
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| 24. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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Long-term safety and efficacy of lacosamide and controlled-release carbamazepine monotherapy in patients with newly diagnosed epilepsy
- 2019
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In: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 60:12, s. 2437-2447
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Journal article (peer-reviewed)abstract
- Objective: A large-scale, double-blind trial (SP0993; NCT01243177) demonstrated that lacosamide was noninferior to controlled-release carbamazepine (carbamazepine-CR) in terms of efficacy, and well tolerated as first-line monotherapy in patients (≥16years of age) with newly diagnosed epilepsy. We report primary safety outcomes from the double-blind extension of the noninferiority trial (SP0994; NCT01465997) and post hoc analyses of pooled long-term safety and efficacy data from both trials. Methods: Patients were randomized 1:1 to lacosamide or carbamazepine-CR. Doses were escalated (lacosamide: 200/400/600mg/d; carbamazepine-CR: 400/800/1200mg/d) based on seizure control. Eligible patients continued randomized treatment in the extension. Primary outcomes of the extension were treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations due to TEAEs. Post hoc analyses of data from combined trials included 12- and 24-month seizure freedom and TEAEs by number of comorbid conditions. Results: A total of 886 patients were treated in the initial trial and 548 in the extension; 211 of 279 patients (75.6%) on lacosamide and 180/269 (66.9%) on carbamazepine-CR completed the extension. In the extension, 181 patients(64.9%) on lacosamide and 182 (67.7%) on carbamazepine-CR reported TEAEs; in both groups, nasopharyngitis, headache, and dizziness were most common. Serious TEAEs were reported by 32 patients (11.5%) on lacosamide and 22 (8.2%) on carbamazepine-CR; 12 (4.3%) and 21 (7.8%) discontinued due to TEAEs. In the combined trials (median exposure: lacosamide 630days; carbamazepine-CR 589days), Kaplan-Meier estimated proportions of patients with 12- and 24-month seizure freedom from first dose were 50.8% (95% confidence interval 46.2%-55.4%) and 47.0% (42.2%-51.7%) on lacosamide, and 54.9% (50.3%-59.6%) and 50.9% (46.0%-55.7%) on carbamazepine-CR. Incidences of drug-related TEAEs and discontinuations due to TEAEs increased by number of comorbid conditions and were lower in patients on lacosamide. Significance: Long-term (median~2years) lacosamide monotherapy was efficacious and generally well tolerated in adults with newly diagnosed epilepsy. Seizurefreedom rates were similar with lacosamide and carbamazepine-CR. © 2019 UCB Biopharma SPRL. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.
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| 25. |
- Ben-Menachem, Elinor, 1945, et al.
(author)
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Long-term safety and tolerability of lacosamide monotherapy in patients with epilepsy: Results from a multicenter, open-label trial
- 2021
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In: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:3
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Journal article (peer-reviewed)abstract
- The primary objective of this trial (SP1042; NCT02582866) was to assess long-term safety and tolerability of lacosamide monotherapy (200-600 mg/day) in adults with focal (partial-onset) seizures or generalized tonic-clonic seizures (without clear focal origin). This Phase III, long-term, open-label, multicenter, follow-up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double-blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment-emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide: 84 (79.2%) completed the trial and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety-six (90.6%), 64 (60.4%), and 44 (41.5%) patients had >= 12, >= 24, and >= 36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (>= 4%) TEAEs were headache (10 [9.4%]), nasopharyngitis (eight [7.5%]), and back pain (five [4.7%]). One (0.9%) patient discontinued due to a TEAE (sudden unexpected death in epilepsy; not considered drug-related), 14 (13.2%) patients reported serious TEAEs, and seven (6.6%) patients reported TEAEs that were considered drug-related. Overall, long-term lacosamide monotherapy was generally well tolerated up to 600 mg/day, with no new safety signals identified.
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