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Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care
In April 2013, the Ministry of Health and Health Sciences Authority of Singapore jointly issued recommendations for HLA-B*15:02 genotyping before starting carbamazepine (CBZ) in new patients of Asian ancestry as standard of care. The Ministry of Health also approved a 75% subsidy for HLA-B*15:02 gen...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221117/ https://www.ncbi.nlm.nih.gov/pubmed/32457602 http://dx.doi.org/10.3389/fphar.2020.00527 |
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author | Sung, Cynthia Tan, Liesbet Limenta, Michael Ganesan, Ganga Toh, Dorothy Chan, Cheng Leng |
author_facet | Sung, Cynthia Tan, Liesbet Limenta, Michael Ganesan, Ganga Toh, Dorothy Chan, Cheng Leng |
author_sort | Sung, Cynthia |
collection | PubMed |
description | In April 2013, the Ministry of Health and Health Sciences Authority of Singapore jointly issued recommendations for HLA-B*15:02 genotyping before starting carbamazepine (CBZ) in new patients of Asian ancestry as standard of care. The Ministry of Health also approved a 75% subsidy for HLA-B*15:02 genotyping to all patients on subsidy at public healthcare institutions. To understand the impact of these regulatory decisions, we researched the usage patterns for CBZ and levetiracetam, the trend of Stevens–Johnson syndrome/toxic epidermal necrolysis [Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)] reports associated with antiepileptic drugs and the take-up rates of HLA-B*15:02 tests in Singapore. In the 5-year post-policy period, we found that the annual number of reported SJS/TEN cases associated with all antiepileptic drugs was significantly decreased by 57% (p = 0.015); SJS/TEN cases associated with CBZ and phenytoin reduced by 92% and 42% respectively. New CBZ users decreased by 31% while new levetiracetam users approximately doubled. The annual number of HLA-B*15:02 tests conducted increased from 444 to approximately 1,200. Regulatory recommendations for HLA-B*15:02 genotyping as standard of care coupled with government subsidy for the test had contributed to a reduction in CBZ SJS/TEN in Singapore by >90%, in line with that observed in other Asian countries with similar policies. Additionally, the number of phenytoin-SJS/TEN cases also declined. Taken together, this represents a successful example of precision medicine through implementation of a genotyping program to reduce a rare but serious adverse drug reaction among at-risk individuals, while preserving the availability of an effective and low-cost medicine for the broader population. |
format | Online Article Text |
id | pubmed-7221117 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72211172020-05-25 Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care Sung, Cynthia Tan, Liesbet Limenta, Michael Ganesan, Ganga Toh, Dorothy Chan, Cheng Leng Front Pharmacol Pharmacology In April 2013, the Ministry of Health and Health Sciences Authority of Singapore jointly issued recommendations for HLA-B*15:02 genotyping before starting carbamazepine (CBZ) in new patients of Asian ancestry as standard of care. The Ministry of Health also approved a 75% subsidy for HLA-B*15:02 genotyping to all patients on subsidy at public healthcare institutions. To understand the impact of these regulatory decisions, we researched the usage patterns for CBZ and levetiracetam, the trend of Stevens–Johnson syndrome/toxic epidermal necrolysis [Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)] reports associated with antiepileptic drugs and the take-up rates of HLA-B*15:02 tests in Singapore. In the 5-year post-policy period, we found that the annual number of reported SJS/TEN cases associated with all antiepileptic drugs was significantly decreased by 57% (p = 0.015); SJS/TEN cases associated with CBZ and phenytoin reduced by 92% and 42% respectively. New CBZ users decreased by 31% while new levetiracetam users approximately doubled. The annual number of HLA-B*15:02 tests conducted increased from 444 to approximately 1,200. Regulatory recommendations for HLA-B*15:02 genotyping as standard of care coupled with government subsidy for the test had contributed to a reduction in CBZ SJS/TEN in Singapore by >90%, in line with that observed in other Asian countries with similar policies. Additionally, the number of phenytoin-SJS/TEN cases also declined. Taken together, this represents a successful example of precision medicine through implementation of a genotyping program to reduce a rare but serious adverse drug reaction among at-risk individuals, while preserving the availability of an effective and low-cost medicine for the broader population. Frontiers Media S.A. 2020-05-07 /pmc/articles/PMC7221117/ /pubmed/32457602 http://dx.doi.org/10.3389/fphar.2020.00527 Text en Copyright © 2020 Sung, Tan, Limenta, Ganesan, Toh and Chan http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Sung, Cynthia Tan, Liesbet Limenta, Michael Ganesan, Ganga Toh, Dorothy Chan, Cheng Leng Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title | Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title_full | Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title_fullStr | Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title_full_unstemmed | Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title_short | Usage Pattern of Carbamazepine and Associated Severe Cutaneous Adverse Reactions in Singapore Following Implementation of HLA-B*15:02 Genotyping as Standard-of-Care |
title_sort | usage pattern of carbamazepine and associated severe cutaneous adverse reactions in singapore following implementation of hla-b*15:02 genotyping as standard-of-care |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221117/ https://www.ncbi.nlm.nih.gov/pubmed/32457602 http://dx.doi.org/10.3389/fphar.2020.00527 |
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