Background When use of a single antiseizure medication (ASM) fails to induce seizure remission, add-on therapy is justified. Perampanel (PER) is approved in Europe as adjunctive therapy for focal, focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures. Aim of the study was to establish whether PER is suitable for first add-on use. Methods A Delphi methodology was adopted to assess consensus on a list of 39 statements produced by an Expert Board of 5 epileptologists. Using an iterative process, statements were finalized by a Delphi Panel of 84 Italian pediatric and adult neurologists. Each statement was rated anonymously to determine level of agreement on a 9-point Likert scale. Consensus was established as agreement by at least 80% of the panelists. The relevance of each statement was also assessed on a 3-point scale. Results Consensus was achieved for 37 statements. Characteristics of PER considered to justify its use as first add-on include evidence of a positive impact on quality of life based on long term retention data, efficacy, tolerability, and ease of use; no worsening of cognitive functions and sleep quality; a low potential for drug interactions; a unique mechanism of action. Potential unfavorable factors are the need for a relatively slow dose titration; the potential occurrence of behavioral adverse effects; lack of information on safety when used in pregnancy; limited access to plasma PER levels. Conclusion Perampanel has many features which justify its use as a first add-on. Choice of an ASM as first add-on should be tailored to individual characteristics.
Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.
Introduction: When monotherapy used alone or sequentially fails to achieve seizure control, a trial of combination therapy may be considered. Objective: To define optimal criteria to guide choice of an antiseizure medication (ASM) for use as first add-on. Methods: A standardized Delphi procedure was applied to produce a list of consensus statements. First, an Expert Board consisting of 5 epileptologists agreed on a set of 46 statements relevant to the objective. The statements were then finalized through an iterative process by a Delphi Panel of 84 Italian pediatric and adult neurologists with expertise in the management of epilepsy. Panel members provided anonymous ratings of their level of agreement with each statement on a 9-point Likert scale. Results: Consensus, defined as agreement by at least 80% of Panel members, was reached for 36 statements. Medication-related factors considered to be important for drug selection included efficacy, tolerability and safety, interaction potential, mechanism of action, and ease of use. The need to optimize adherence and to tailor drug selection to individual characteristics was emphasized. Conclusions: Choice of an ASM for first add-on requires consideration of many factors, many of which also apply to choose initial treatment. Factors more specifically relevant to add-on use include drug interaction potential and the preference for an ASM with a different mechanism of action.
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