Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data

Rohracher, Alexandra; Zimmermann, Georg; Villanueva, Vicente; Garamendi, Íñigo; Sander, Josemir W.; Wehner, Tim; Shankar, Rohit; Ben‐Menachem, Elinor; Brodie, Martin J.; Pensel, Max Christian; Gennaro, Giancarlo Di; Maurousset, Aude; Strzelczyk, Adam; Rheims, Sylvain; Rácz, A.; Menzler, Katja; Bertol-Alegre, Vicente; García‐Morales, Irene; López‐González, Francisco Javier; Toledo, Manuel; Carpenter, Katherine; Trinka, Eugen

doi:10.1111/epi.14520

Cited by 74 publications

(101 citation statements)

References 48 publications

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“…Compared to other so-called real-life observational survey including reports from our center [4,[9][10][11][18][19][20] the responder rates were relatively low and the incidence of adverse events relatively high. The easiest explanation for this discrepancy is that in the cohort investigated here we only included in-patients where in most other observational surveys out-patients predominated.…”

Section: Discussionmentioning

confidence: 65%

“…Even more, we saw a similar phenomenon concerning tolerability: 23% (n = 7) of patients with adverse events showed plasma levels below 180 ng/ml and 7% (n = 2) showed plasma levels below 86 ng/ml. The most common adverse events with PER are somnolence and dizziness [3][4][5]8,10,11,14]. If somnolence occurred, it was observed at levels between 133 ng/ml and 744 ng/ml.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma samples were drawn between 7.30 and 7.45 o'clock the next morning under fasting conditions. Because of the long half-life of approximately 105 h without the influence of enzyme-inducing drugs that reduce the elimination half-life markedly, [3,5,[7][8][9][10][11][12][13] PER plasma concentrations were measured only if the PER dose had been stable for at least 3 weeks. A stable plasma steady state is reached within 10-19 days after increases or decreases of the PER dose [7].…”

Section: Methodsmentioning

confidence: 99%

“…PER is the first in-class, selective, noncompetitive alpha-amino-3hydroxy-5-methyl-4-isoxazolepropionate acid (AMPA) receptor antagonist used in epilepsy therapy [3][4][5] that was introduced to the German market in 2012 [2]. Because of its pharmacokinetic profile with an elimination half-life of up to 105 h, once daily dosing at bedtime is recommended [3][4][5][6][7][8][9][10][11][12]. Potent cytochrome (CYP)3A4 inducers, such as carbamazepine, phenytoin, or oxcarbazepine, may markedly accelerate the elimination half-life time to approximately 25 h and decrease plasma concentrations of PER [3,5,[7][8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

“…Because of its pharmacokinetic profile with an elimination half-life of up to 105 h, once daily dosing at bedtime is recommended [3][4][5][6][7][8][9][10][11][12]. Potent cytochrome (CYP)3A4 inducers, such as carbamazepine, phenytoin, or oxcarbazepine, may markedly accelerate the elimination half-life time to approximately 25 h and decrease plasma concentrations of PER [3,5,[7][8][9][10][11][12][13]. This resulted in less efficacy in the pivotal phase III trials as an adjunct, although still statistically significant superiority over placebo was apparent [14].…”

Section: Introductionmentioning

confidence: 99%

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Plasma concentration and clinical effects of perampanel—The Kork experience

Steinhoff

Hübers

Kurth

et al. 2019

Seizure

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A B S T R A C TPurpose: To investigate the correlation between steady-state plasma concentrations of perampanel (PER) with efficacy and tolerability in adult patients with difficult-to-treat epilepsy. Methods: PER plasma concentrations were assessed at steady-state conditions in 92 adult patients (57% female, 43% male, mean age 39,5 years, age range 20-73 years). All patients had been treated with PER at a stable dose for at least 3 weeks. Clinical efficacy was assessed on the day of measuring the plasma concentrations by a retrospective analysis of the seizure frequency and adverse effects. Results: The mean overall plasma concentration was 323,5 ng/ml (range 19 ng/ml -2436 ng/ml). The corresponding mean dose was 7,5 mg (range 2 mg -12 mg). PER dose and plasma concentration showed a close linear correlation. Plasma levels and doses varied widely concerning both efficacy and tolerability of PER. The differences between plasma levels of responders and non-responders were not statistically significant. Therefore a clinically useful general reference range could not be defined. Conclusion: Our data do not indicate a reliable therapeutic range for PER plasma concentrations. Individual reference ranges varied widely. Therapeutic drug monitoring (TDM) may still be helpful in certain clinical situations.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma concentration and clinical effects of perampanel—The Kork experience

Steinhoff

Hübers

Kurth

et al. 2019

Seizure

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PROVE: Retrospective, non‐interventional, Phase IV study of perampanel in real‐world clinical care of patients with epilepsy

et al. 2022

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Objective To assess retention, dosing, efficacy, and safety of perampanel in a large cohort of patients with epilepsy during routine clinical care. Methods PROVE was a retrospective, non‐interventional Phase IV study (NCT03208660). Data were obtained retrospectively from the medical records of patients in the United States initiating perampanel after January 1, 2014, according to treating clinicians' recommendation. Retention rate was the primary efficacy endpoint. Secondary efficacy endpoints included median percent changes in seizure frequency per 28 days from baseline, seizure‐freedom rate, and overall investigator impression of seizure effect. Safety endpoints included incidence of treatment‐emergent adverse events (TEAEs). Efficacy and safety were also assessed according to baseline use of enzyme‐inducing antiseizure medications (EIASMs). Results Overall, 1703 patients were enrolled and included in the Safety Analysis Set (SAS; ≥1 baseline EIASMs, n = 358 [21.0%]; no baseline EIASMs, n = 1345 [79.0%]). Mean (standard deviation [SD]) cumulative duration of exposure to perampanel was 17.4 (15.7) months; mean (SD) daily perampanel dose was 5.6 (2.7) mg. The most frequent perampanel titration intervals were weekly (23.4%) and every 2 weeks (24.7%). Across the SAS, 24‐month retention rate was 48.1% (n = 501/1042). Based on overall investigator impression at the end of treatment, 51.9%, 35.8%, and 12.3% of patients in the SAS experienced improvement, no change, or worsening of seizures, respectively. TEAEs occurred in 704 (41.3%) patients; 79 (4.6%) had serious TEAEs. The most common TEAE was dizziness (7.3%). There was some variation in efficacy according to EIASM use, while retention rates and safety were generally consistent. Significance In this final analysis of >1700 patients with epilepsy receiving perampanel in routine clinical care, favorable retention and sustained efficacy were demonstrated for ≥12 months.

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Effectiveness and safety of mono‐ and add‐on perampanel in pediatric patients with epilepsy: Experience from a single‐center retrospective study

Li,

Guo,

et al. 2023

Epilepsia Open

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ObjectiveTo evaluate the effectiveness and safety of perampanel (PER) monotherapy (MT) or add‐on therapy (AT) in Chinese children with epilepsy, as well as to evaluate the data from routine therapeutic drug monitoring (TDM) of PER for these pediatric patients.MethodsThis retrospective and observational study was carried out on children with epilepsy (n = 340) from 2020 to 2022 at the Children's Hospital of Nanjing Medical University. Outcome measures were the responder rate (50% or greater seizure reduction), long‐term efficacy, and tolerability (number and types of adverse events) in MT and AT groups. Concentrations of plasma PER obtained from these patients, if available, were analyzed too.ResultsA total of 279 patients achieved at least 3 months of therapy, and 58.1% responded to PER therapy. 53 of the responders were seizure‐free (32.7%). The retention rate dropped from 88.0% at 3 months to 40.6% at 12 months after treatment. Patients with MT achieved better seizure control than those with AT (P <0.001). Intriguingly, PER exerted a very weak effect on patients who took more than 2 ASMs or were diagnosed with drug‐resistant epilepsy. There were no significant differences in tolerability between the two groups. In addition, 179 patients were routinely monitored for PER, and the trough concentrations (C0) for these patients ranged from 30.0 to 992.0 ng/mL. However, no significant difference in C0 was observed between responders and nonresponders (333 ng/mL vs 325.5 ng/mL, P = 0.264).SignificanceThis study provides effectiveness and safety data on Chinese children with epilepsy treated with PER either as MT or as AT. The efficacy of patients receiving MT was much better than cases administered with more than 2 ASMs or diagnosed with drug‐resistant epilepsy. In addition, no association was found between the plasma PER concentration and efficacy or safety.

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Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data

Cited by 74 publications

References 48 publications

Plasma concentration and clinical effects of perampanel—The Kork experience

Plasma concentration and clinical effects of perampanel—The Kork experience

PROVE: Retrospective, non‐interventional, Phase IV study of perampanel in real‐world clinical care of patients with epilepsy

Effectiveness and safety of mono‐ and add‐on perampanel in pediatric patients with epilepsy: Experience from a single‐center retrospective study

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