Testing the nonclinical Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm with an established anti-seizure medication: Levetiracetam case study.

Levetiracetam (LEV), a well-established anti-seizure medication (ASM), was launched before the original ICH S7B nonclinical guidance assessing QT prolongation potential and the introduction of the Comprehensive In Vitro Proarrhythmia Assay (CiPA) paradigm. No information was available on its effects on cardiac channels. The goal of this work was to "pressure test" the CiPA approach with LEV and check the concordance of nonclinical core and follow-up S7B assays with clinical and post-marketing data.

Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union.

Background: Sodium oxybate (Xyrem), approved by the European Medicines Agency (EMA) for narcolepsy with cataplexy, is only available through risk mitigation programs due to potential adverse effects including respiratory and central nervous system depression, neuropsychiatric events, and misuse.

Objective: We report findings from a survey evaluating effectiveness of the European Union Xyrem Risk Management Plan (RMP).

Patients And Methods: A cross-sectional, online, multiple-choice survey was distributed to randomly selected healthcare professionals (HCPs) from six European countries (April 2016-May 2018).

Long-term compliance, safety, and tolerability of sodium oxybate treatment in patients with narcolepsy type 1: a postauthorization, noninterventional surveillance study.

Study Objectives: To evaluate adherence to sodium oxybate prescribing information for indication and dosage, patients' compliance with instructions for use, safety/tolerability in routine clinical practice, and abuse potential.

Methods: A postauthorization, noninterventional surveillance study (NCT00244465) in patients who were prescribed sodium oxybate according to current practice by sleep disorders specialists. Patients were monitored for ≤18 months.

Safety of cetirizine in pregnancy.

Managing symptoms of allergic rhinitis (AR) and urticaria in pregnant women is important to reduce complications and negative outcomes. The objective of this study was to provide information on the pregnancy outcomes of women exposed to the antihistamine cetirizine (CTZ). The UCB Pharma Patient Safety Database was searched for pregnancies up to 28 February 2015.

Risk of QT prolongation and torsade de pointes associated with exposure to hydroxyzine: re-evaluation of an established drug.

Several noncardiac drugs have been linked to cardiac safety concerns, highlighting the importance of post-marketing surveillance and continued evaluation of the benefit-risk of long-established drugs. Here, we examine the risk of QT prolongation and/or torsade de pointes (TdP) associated with the use of hydroxyzine, a first generation sedating antihistamine. We have used a combined methodological approach to re-evaluate the cardiac safety profile of hydroxyzine, including: (1) a full review of the sponsor pharmacovigilance safety database to examine real-world data on the risk of QT prolongation and/or TdP associated with hydroxyzine use and (2) nonclinical electrophysiological studies to examine concentration-dependent effects of hydroxyzine on a range of human cardiac ion channels.

Brivaracetam in Unverricht-Lundborg disease (EPM1): Results from two randomized, double-blind, placebo-controlled studies.

Objective: To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1).

Methods: Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (≥16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score ≥30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up-titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study.