Lamotrigine: Difference between revisions
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{{MedTemplate | {{MedTemplate | ||
| generic | | generic = Lamotrigine | ||
| brand | | brand = Lamictal (IR), Lamictal XR, Lamictal ODT | ||
| structure | | structure = | ||
| classes | | classes = [[:Category:Anticonvulsants|Anticonvulsant]], [[:Category:Mood stabilizers|Mood stabilizer]], [[:Category:Sodium channel blockers|Sodium channel blocker]] | ||
| | | 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) | ||
| fda_max = | | pill_id = | ||
| routes | | routes = Oral | ||
| onset | | onset = Antiepileptic effect within days at therapeutic level; mood-stabilizing effect emerges over weeks | ||
| duration | | duration = 24 hours (often divided BID at higher doses) | ||
| halflife | | 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> | ||
| bioavailability = ~98% (oral)<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" /> | |||
| | | 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). The HLA-B*15:02 allele substantially elevates SJS risk in Asian populations; CPIC and FDA support pre-treatment HLA-B*15:02 testing in at-risk patients<ref name="cpic-hla">CPIC Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine, applicable by extension to lamotrigine. https://cpicpgx.org/guidelines/guideline-for-carbamazepine-and-hla-b/</ref>. | ||
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}} | }} | ||
== References == | |||
<references /> | |||
[[Category:Anticonvulsants]] | |||
[[Category:Mood stabilizers]] | [[Category:Mood stabilizers]] | ||
[[Category:Sodium channel blockers]] | [[Category:Sodium channel blockers]] | ||
Revision as of 06:41, 23 May 2026
Lamotrigine
Lamictal (IR), Lamictal XR, Lamictal ODT
Experience
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Summary
Common uses
Partial-onset and generalized tonic-clonic seizures (FDA, adjunct or monotherapy)0, Lennox-Gastaut syndrome (FDA)0, Bipolar I disorder maintenance, particularly prevention of depressive episodes (FDA)0, Bipolar depression, acute (off-label, modest evidence)0
Pharmacy
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
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
US FDA Max
400 mg/day (bipolar monotherapy); 700 mg/day (epilepsy with enzyme-inducing comedication)
Pharmacology
Routes
Oral
Onset
Antiepileptic effect within days at therapeutic level; mood-stabilizing effect emerges over weeks
Duration
24 hours (often divided BID at higher doses)
Half-life
~25-33 hours alone; ~15 hours with enzyme inducers; ≥60 hours with valproate (UGT inhibition)[2]
Bioavailability
~98% (oral)[2]
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[2]
Legal status
Purported mechanism
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.0 Metabolized predominantly by UGT1A4 glucuronidation (not CYP), which is why valproate doubles exposure (UGT inhibition) and carbamazepine, phenytoin, rifampin halve exposure (UGT induction). The HLA-B*15:02 allele substantially elevates SJS risk in Asian populations; CPIC and FDA support pre-treatment HLA-B*15:02 testing in at-risk patients[1].
References
- ↑ CPIC Guideline for HLA Genotype and Use of Carbamazepine and Oxcarbazepine, applicable by extension to lamotrigine. https://cpicpgx.org/guidelines/guideline-for-carbamazepine-and-hla-b/
- ↑ 2.0 2.1 2.2 2.3 FDA Prescribing Information, Lamictal (lamotrigine), GSK, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020241s045s051lbl.pdf