Lamotrigine: Difference between revisions
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MDElliottMD (talk | contribs) parser-claude: Lamotrigine MedTemplate refill, Top 300 stub upgrade |
MDElliottMD (talk | contribs) home-claude: fix CPIC citation hard errors (CPIC scope does not cover these medicines; correct to PharmGKB/DPWG/FDA label where applicable) |
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| pregnancy = '''Among the safest mood stabilizers in pregnancy''' with reassuring monotherapy registry data, in sharp contrast to valproate. Estrogen-containing contraceptives accelerate lamotrigine metabolism, requiring dose adjustments at start and stop of contraception<ref name="lamictal-label" /> | | pregnancy = '''Among the safest mood stabilizers in pregnancy''' with reassuring monotherapy registry data, in sharp contrast to valproate. Estrogen-containing contraceptives accelerate lamotrigine metabolism, requiring dose adjustments at start and stop of contraception<ref name="lamictal-label" /> | ||
| legal = [[USLegal:Prescription only|Rx-only]] in US. Carries the FDA '''Boxed Warning for serious skin reactions''' including Stevens-Johnson syndrome and toxic epidermal necrolysis, with the risk concentrated in the first 2-8 weeks of therapy and elevated by rapid titration<ref name="lamictal-label" /> | | legal = [[USLegal:Prescription only|Rx-only]] in US. Carries the FDA '''Boxed Warning for serious skin reactions''' including Stevens-Johnson syndrome and toxic epidermal necrolysis, with the risk concentrated in the first 2-8 weeks of therapy and elevated by rapid titration<ref name="lamictal-label" /> | ||
| mechanism = <vote slug="lamotrigine-mech-claim">Voltage-gated sodium channel blocker in the inactivated state, reducing high-frequency repetitive neuronal firing and consequently reducing presynaptic glutamate release. The mood-stabilizing mechanism is incompletely characterized but is plausibly the same glutamatergic dampening applied to limbic circuits.</vote> Metabolized predominantly by UGT1A4 glucuronidation (not CYP), which is why '''valproate doubles exposure''' (UGT inhibition) and '''carbamazepine, phenytoin, rifampin halve exposure''' (UGT induction). | | mechanism = <vote slug="lamotrigine-mech-claim">Voltage-gated sodium channel blocker in the inactivated state, reducing high-frequency repetitive neuronal firing and consequently reducing presynaptic glutamate release. The mood-stabilizing mechanism is incompletely characterized but is plausibly the same glutamatergic dampening applied to limbic circuits.</vote> Metabolized predominantly by UGT1A4 glucuronidation (not CYP), which is why '''valproate doubles exposure''' (UGT inhibition) and '''carbamazepine, phenytoin, rifampin halve exposure''' (UGT induction). HLA-B*15:02 is associated with lamotrigine-induced SJS/TEN in Asian populations, but the association is weaker than for carbamazepine.<ref name="zeng2015lam">Zeng T, Long YS, Min FL, Liao WP. Association of HLA-B*1502 allele with lamotrigine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese subjects: a meta-analysis. Int J Dermatol. 2015;54(4):488-493. PMID 25428396.</ref> In European-ancestry patients, HLA-B*38:01 has been identified as a risk allele for lamotrigine-induced SJS.<ref name="kazeem2009lam">Kazeem GR, Cox C, Aponte J, Messenheimer J. High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenet Genomics. 2009;19(9):661-665. PMID 19668019.</ref> The FDA Lamictal label notes HLA-B*15:02 as a risk factor for lamotrigine SJS/TEN in patients of Asian ancestry but does not require pre-treatment HLA testing for lamotrigine as the carbamazepine label does.<ref name="lamictal-label" /> CPIC has published a guideline for carbamazepine and oxcarbazepine HLA testing; no formal CPIC guideline for lamotrigine HLA testing has been published. | ||
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