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Lamotrigine: Difference between revisions

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{{MedTemplate
{{MedTemplate
| generic           = Lamotrigine
| generic           = Lamotrigine
| brand             = Lamictal
| brand             = Lamictal (IR), Lamictal XR, Lamictal ODT
| structure         =  
| structure         =
| classes           = Mood Stabilizer, Anticonvulsant
| classes           = [[:Category:Anticonvulsants|Anticonvulsant]], [[:Category:Mood stabilizers|Mood stabilizer]], [[:Category:Sodium channel blockers|Sodium channel blocker]]
| mechanism          = Sodium channel blocker; inhibits glutamate release
| uses             = <vote slug="partial-seizures-use">Partial-onset and generalized tonic-clonic seizures (FDA, adjunct or monotherapy)</vote>, <vote slug="lennox-gastaut-use">Lennox-Gastaut syndrome (FDA)</vote>, <vote slug="bipolar-maintenance-use">Bipolar I disorder maintenance, particularly prevention of depressive episodes (FDA)</vote>, <vote slug="bipolar-depression-acute-use">Bipolar depression, acute (off-label, modest evidence)</vote>
| uses               =  
| starting_dose     = '''Slow titration is essential to mitigate Stevens-Johnson syndrome risk.''' Standard adult: 25 mg PO daily for 2 weeks, then 50 mg daily for 2 weeks, then 100 mg daily for 1 week, then 200 mg daily target. Double the rate if on enzyme inducers (carbamazepine, phenytoin); halve the rate if on valproate
| starting_dose     =  
| preparations     = IR tablets 25, 100, 150, 200 mg; chewable dispersible tablets 2, 5, 25 mg; ODT 25, 50, 100, 200 mg; XR tablets 25, 50, 100, 200, 250, 300 mg
| preparations       =  
| fda_max          = 400 mg/day (bipolar monotherapy); 700 mg/day (epilepsy with enzyme-inducing comedication)
| routes            =  
| pill_id           =
| onset              =
| routes            = Oral
| duration           =  
| onset            = Antiepileptic effect within days at therapeutic level; mood-stabilizing effect emerges over weeks
| halflife          =  
| duration         = 24 hours (often divided BID at higher doses)
| bioavailability    =  
| halflife          = ~25-33 hours alone; ~15 hours with enzyme inducers; '''≥60 hours with valproate''' (UGT inhibition)<ref name="lamictal-label">FDA Prescribing Information, Lamictal (lamotrigine), GSK, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf</ref>
| pregnancy         =  
| bioavailability   = ~98% (oral)<ref name="lamictal-label" />
| legal              =  
| 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" />
| intro              =  
| 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" />
| pharmacokinetics   =  
| 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.
| pharmacodynamics  =  
| indications        =  
| dosing             =  
| effects            =  
| contraindications  =
| interactions      =
| pregnancy_details  =
| monitoring         =  
| counseling        =  
| anecdotes          =  
| seealso            =  
| references        =  
}}
}}


[[Category:Mood_Stabilizers]]
== References ==
<references />


[[Category:Anticonvulsants]]
[[Category:Mood stabilizers]]
[[Category:Sodium channel blockers]]
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