Psychiatry and clinical neurosciences · 2025
Flunitrazepam increases the risk of lamotrigine-induced cutaneous adverse reactions: Combined analysis of medical big data and clinical research.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Bando Hiroshi, Goda Mitsuhiro, Nakataki Masahito, Hirai Keita, Nitta Yuki, Kawada Kei, Yoshioka Toshihiko, Kanda Masaya, Ogawa Atsushi, Mukuta-Murakami Chiaki, Tsujinaka Kaito, Miyata Koji, Kitagawa Kohei, Niimura Takahiro, Aizawa Fuka, Yagi Kenta, Izawa-Ishizawa Yuki, Chuma Masayuki, Naito Takafumi, Tasaki Yoshikazu, Numata Shusuke, Ishizawa Keisuke
Аннотация
AIM: The concomitant use of lamotrigine and valproic acid, a uridine diphosphate (UDP)-glucuronosyltransferase inhibitor, is a known risk factor for lamotrigine-induced rashes, which may develop into fatal or severe cutaneous adverse reactions. No drugs other than valproic acid have been shown to increase lamotrigine concentrations in humans by inhibiting UDP-glucuronosyltransferase. The treatment of bipolar disorder and epilepsy is often combined with other medications, which may affect the risk of rash. We aimed to identify medications that increased the risk of lamotrigine-induced rashes using clinical data.
METHODS: We used VigiBase to search for drugs associated with the increased number of reported severe cutaneous adverse reactions when combined with lamotrigine. In a retrospective study, we collected information on patients from electronic medical records and used propensity score matching to compare the incidence of lamotrigine-induced rash with and without flunitrazepam use. Furthermore, we compared lamotrigine concentrations between patients treated with and without flunitrazepam in a prospective observational study.
RESULTS: VigiBase analysis showed that flunitrazepam significantly increased the reporting odds ratio for lamotrigine-related severe cutaneous adverse reactions. In the retrospective study, combining lamotrigine with flunitrazepam significantly increased the incidence of rashes. In the prospective observational study, lamotrigine with flunitrazepam significantly increased the concentration-to-dose ratio.
CONCLUSION: Flunitrazepam use may affect lamotrigine concentration and increase the risk of rash. These results have implications for the choice of sleep medication. In addition, when lamotrigine is used in combination with flunitrazepam, the lamotrigine dosing design should address lamotrigine-induced rash management.
METHODS: We used VigiBase to search for drugs associated with the increased number of reported severe cutaneous adverse reactions when combined with lamotrigine. In a retrospective study, we collected information on patients from electronic medical records and used propensity score matching to compare the incidence of lamotrigine-induced rash with and without flunitrazepam use. Furthermore, we compared lamotrigine concentrations between patients treated with and without flunitrazepam in a prospective observational study.
RESULTS: VigiBase analysis showed that flunitrazepam significantly increased the reporting odds ratio for lamotrigine-related severe cutaneous adverse reactions. In the retrospective study, combining lamotrigine with flunitrazepam significantly increased the incidence of rashes. In the prospective observational study, lamotrigine with flunitrazepam significantly increased the concentration-to-dose ratio.
CONCLUSION: Flunitrazepam use may affect lamotrigine concentration and increase the risk of rash. These results have implications for the choice of sleep medication. In addition, when lamotrigine is used in combination with flunitrazepam, the lamotrigine dosing design should address lamotrigine-induced rash management.