Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database

Objectives This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified. Design This is a retrospective review of suspected adverse drug reaction (ADR)...

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Main Authors: Egunsola, Oluwaseun, Star, Kristina, Juhlin, Kristina, Kardaun, Sylvia, Choonara, Imti, Sammons, Helen
Format: Article
Published: BMJ 2017
Online Access:https://eprints.nottingham.ac.uk/47339/
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author Egunsola, Oluwaseun
Star, Kristina
Juhlin, Kristina
Kardaun, Sylvia
Choonara, Imti
Sammons, Helen
author_facet Egunsola, Oluwaseun
Star, Kristina
Juhlin, Kristina
Kardaun, Sylvia
Choonara, Imti
Sammons, Helen
author_sort Egunsola, Oluwaseun
building Nottingham Research Data Repository
collection Online Access
description Objectives This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified. Design This is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR. Setting Reports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015. Patients Data for patients aged ≤17 years old were extracted. Results There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/ TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10–22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)). Conclusions The results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period.
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spelling nottingham-473392020-05-04T18:58:59Z https://eprints.nottingham.ac.uk/47339/ Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database Egunsola, Oluwaseun Star, Kristina Juhlin, Kristina Kardaun, Sylvia Choonara, Imti Sammons, Helen Objectives This study aims to characterise paediatric reports with lamotrigine (LTG) and Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN), and to explore whether potential risk factors can be identified. Design This is a retrospective review of suspected adverse drug reaction (ADR) reports. Reported time from LTG start to SJS/TEN onset, indication for use and dose was explored. To identify potential risk groups, report features (eg, ages, patient sex, co-reported drugs) for LTG and SJS/TEN were contrasted with two reference groups in the same database, using shrinkage logOR. Setting Reports were retrieved from VigiBase, the WHO global database of individual case safety reports, in January 2015. Patients Data for patients aged ≤17 years old were extracted. Results There were 486 reports of SJS/TEN in LTG-treated paediatric patients. Ninety-seven per cent of the cases with complete information on time to onset of SJS/ TEN occurred within 8 weeks of initiation of LTG therapy. The median time to onset was 15 days (IQR: 10–22 days). The proportion of SJS/TEN with LTG and valproic acid (VPA) co-reporting was significantly more than non-cutaneous ADRs (43% vs 19%, (logOR: 1.60 (99% CI: 1.33 to 1.84)). Conclusions The results suggest that VPA co-medication with LTG therapy is a risk factor for SJS/TEN in the paediatric population. Although this relationship has been identified from individual case reports, this is the first supportive study from a large compilation of cases. SJS/TEN risk is highest in first 8 weeks of treatment with LTG in children and clinicians should be aware of this risk during this period. BMJ 2017-08-04 Article PeerReviewed Egunsola, Oluwaseun, Star, Kristina, Juhlin, Kristina, Kardaun, Sylvia, Choonara, Imti and Sammons, Helen (2017) Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database. BMJ Paediatrics Open, 1 . e000039. ISSN 2399-9772 http://bmjpaedsopen.bmj.com/content/1/1/e000039 doi:10.1136/bmjpo-2017-000039 doi:10.1136/bmjpo-2017-000039
spellingShingle Egunsola, Oluwaseun
Star, Kristina
Juhlin, Kristina
Kardaun, Sylvia
Choonara, Imti
Sammons, Helen
Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title_full Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title_fullStr Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title_full_unstemmed Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title_short Retrospective review of paediatric case reports of Stevens-Johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
title_sort retrospective review of paediatric case reports of stevens-johnson syndrome and toxic epidermal necrolysis with lamotrigine from an international pharmacovigilance database
url https://eprints.nottingham.ac.uk/47339/
https://eprints.nottingham.ac.uk/47339/
https://eprints.nottingham.ac.uk/47339/