Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome
Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Case Reports in Medicine |
| Online Access: | http://dx.doi.org/10.1155/2018/5371854 |
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| author | Marta Vázquez Cecilia Maldonado Natalia Guevara Andrea Rey Pietro Fagiolino Antonella Carozzi Carlos Azambuja |
| author_facet | Marta Vázquez Cecilia Maldonado Natalia Guevara Andrea Rey Pietro Fagiolino Antonella Carozzi Carlos Azambuja |
| author_sort | Marta Vázquez |
| collection | DOAJ |
| description | Lamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens–Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Hereby, we present the case of an 8-year-old boy who suffered from SJS and other complications two weeks after LTG was added to his VPA treatment in order to control his seizures. VPA is known to decrease LTG clearance via reduced glucuronidation. In this case, the minor elimination pathway of LTG would play a more important role, and the formation of an arene oxide metabolite would be enhanced. As this reactive metabolite is detoxified mainly by enzymatic reactions, involving microsomal epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or GSH-S-transferases is either defective or inhibited or a depletion of intracellular glutathione levels is taking place. VPA can cause inhibition of epoxide hydrolase enzymes and/or depletion of glutathione levels leading to adverse cutaneous reactions. |
| format | Article |
| id | doaj-art-3bec99c4d5f84706bd1c1716a49b0a21 |
| institution | Kabale University |
| issn | 1687-9627 1687-9635 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Case Reports in Medicine |
| spelling | doaj-art-3bec99c4d5f84706bd1c1716a49b0a212025-02-03T05:57:58ZengWileyCase Reports in Medicine1687-96271687-96352018-01-01201810.1155/2018/53718545371854Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson SyndromeMarta Vázquez0Cecilia Maldonado1Natalia Guevara2Andrea Rey3Pietro Fagiolino4Antonella Carozzi5Carlos Azambuja6Department of Pharmaceutical Sciences, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, 11800 Montevideo, UruguayDepartment of Pharmaceutical Sciences, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, 11800 Montevideo, UruguayDepartment of Pharmaceutical Sciences, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, 11800 Montevideo, UruguayDepartment of Neuropediatrics, Faculty of Medicine, Universidad de la República, Avenida General Flores 2125, 11800 Montevideo, UruguayDepartment of Pharmaceutical Sciences, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, 11800 Montevideo, UruguayGenia-Genetics Molecular Laboratory, Bulevar General Artigas 922, 11300 Montevideo, UruguayGenia-Genetics Molecular Laboratory, Bulevar General Artigas 922, 11300 Montevideo, UruguayLamotrigine (LTG) is currently indicated as adjunctive therapy for focal and generalized tonic-clonic seizures and for treatment of bipolar disorder and neuropathic pain. A common concern with LTG in children is the frequency of appearance of skin rash. The intensity of this adverse effect can vary from transient mild rash to Stevens–Johnson syndrome (SJS), which can be fatal mainly when LTG is coadministered with valproic acid (VPA). Hereby, we present the case of an 8-year-old boy who suffered from SJS and other complications two weeks after LTG was added to his VPA treatment in order to control his seizures. VPA is known to decrease LTG clearance via reduced glucuronidation. In this case, the minor elimination pathway of LTG would play a more important role, and the formation of an arene oxide metabolite would be enhanced. As this reactive metabolite is detoxified mainly by enzymatic reactions, involving microsomal epoxide hydrolase and/or GSH-S-transferases and these enzymes are polymorphically expressed in humans, arene oxide toxicity is increased when epoxide hydrolase or GSH-S-transferases is either defective or inhibited or a depletion of intracellular glutathione levels is taking place. VPA can cause inhibition of epoxide hydrolase enzymes and/or depletion of glutathione levels leading to adverse cutaneous reactions.http://dx.doi.org/10.1155/2018/5371854 |
| spellingShingle | Marta Vázquez Cecilia Maldonado Natalia Guevara Andrea Rey Pietro Fagiolino Antonella Carozzi Carlos Azambuja Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome Case Reports in Medicine |
| title | Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome |
| title_full | Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome |
| title_fullStr | Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome |
| title_full_unstemmed | Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome |
| title_short | Lamotrigine-Valproic Acid Interaction Leading to Stevens–Johnson Syndrome |
| title_sort | lamotrigine valproic acid interaction leading to stevens johnson syndrome |
| url | http://dx.doi.org/10.1155/2018/5371854 |
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