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Paediatric Postmarketing Pharmacovigilance Using Prescription-Event Monitoring

Comparison of the Adverse Event Profiles of Lamotrigine Prescribed to Children and Adults in England

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Abstract

Background: Using postmarketing pharmacovigilance data collected shortly after market authorization of lamotrigine in the UK, a study was conducted to compare the adverse event (AE) profiles of children and adults taking lamotrigine, using modified signal detection methods.

Methods: Data from the lamotrigine Prescription Event Monitoring (PEM) study, an observational cohort study, were stratified by age and examined using summary statistics for adverse drug reactions (ADRs), reasons for stopping treatment, deaths and follow-up information. Incidence densities of AEs in children (0–17 years) and adults (≥18 years) in the first month of treatment were compared with months 2–6 to examine whether the AE rates were different in these two periods. AE rates in children were compared with those in adults (proportional reporting ratio [PRR] and incidence rate ratios), to compare the AE profiles between these age groups.

Results: The cohort included 2457 children and 7379 adults. Differences in the AE profiles between children and adults were observed. Rash (PRR 1.2) and Stevens-Johnson syndrome (PRR 4.5) were more commonly reported in children, and confusion more frequently in adults (PRR 6.3). In children, 33% of ADRs were reported to the Regulatory Authority compared with 44% in adults. A higher proportion of children stopped treatment due to lack of effectiveness (45% vs 38%). No deaths were attributed to lamotrigine.

Conclusions: This study demonstrated that signal detection methods can be used to detect quantitative and qualitative differences in the AE profiles between the first children and adults taking a newly licensed drug.

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Acknowledgements

We would like to record our keen appreciation of the cooperation of the general practitioners and numerous other colleagues, including Mr Shayne Freemantle, who have helped in this study. We would also like to thank, for their important participation, the Prescription Pricing Division of the NHS Business Services Authority (formerly known as the Prescription Pricing Authority) in England. In addition, we wish to thank Mrs Lesley Flowers for assistance with the preparation of this manuscript.

The Drug Safety Research Unit (DSRU) is a registered independent charity (no. 327206). It receives unconditional donations from pharmaceutical companies. The companies have no control over the conduct or publication of the studies conducted by the DSRU. The Unit has received such funds from Wellcome, the original manufacturer of lamotrigine. After the conclusion and initial report of this study, B. Aurich-Barrera took up employment with GlaxoSmithKline in 2006 (which merged in 2001 with Wellcome) and later, in October 2009, took up employment with Novartis. L. Wilton, D. Brown and S. Shakir have declared no conflicts of interest related to the content of this study.

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Authors and Affiliations

  1. Drug Safety Research Unit, Bursledon Hall, Blundell Lane, SO31 1AA, Southampton, UK

    Beate Aurich-Barrera, Lynda Wilton, David Brown &  Saad Shakir

  2. Division of Pharmacy Practice, School of Pharmacy and Biomedical Sciences, Portsmouth University, Portsmouth, UK

    Beate Aurich-Barrera, Lynda Wilton, David Brown &  Saad Shakir

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  1. Beate Aurich-Barrera
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  2. Lynda Wilton
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  3. David Brown
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  4. Saad Shakir
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Correspondence to Saad Shakir.

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Aurich-Barrera, B., Wilton, L., Brown, D. et al. Paediatric Postmarketing Pharmacovigilance Using Prescription-Event Monitoring. Drug-Safety 33, 751–763 (2010). https://doi.org/10.2165/11536830-000000000-00000

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