Lamotrigine is an antiepileptic medicine used in epilepsy (partial-onset seizures, primary generalised tonic-clonic seizures and Lennox-Gastaut syndrome) and for the maintenance treatment of bipolar disorder. The dose is increased slowly to avoid skin rashes, which can be serious. It should not be stopped suddenly.
Also known as: Lamictal
Combining Lamotrigine with Carbamazepine reduces Lamotrigine concentrations, possibly requiring a higher dose; Lamotrigine may also increase the toxicity of the Carbamazepine metabolite.
The interaction is bidirectional: carbamazepine induces lamotrigine glucuronidation and reduces its concentrations by about 40–50%, potentially requiring a lamotrigine dose increase; conversely, lamotrigine inhibits epoxide hydrolase and can raise the active metabolite carbamazepine-10,11-epoxide, causing toxicity (nystagmus, ataxia, diplopia) even with carbamazepine levels in range. Titrate lamotrigine according to response, watch for epoxide toxicity signs and consider epoxide monitoring if available.
Carbamazepine + lamotrigine: carbamazepine lowers lamotrigine levels (glucuronidation induction) and lamotrigine may raise carbamazepine-epoxide. Monitor both.
Carbamazepine induces the glucuronidation of Lamotrigine, lowering its levels; Lamotrigine may raise carbamazepine-10,11-epoxide, increasing toxicity.
Monitor seizure control and signs of neurological toxicity (diplopia, ataxia).
Rash or signs of a serious reaction require discontinuation and evaluation.
Adjust the Lamotrigine dose according to response and, if available, serum levels; watch for neurological toxicity.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Combining Valproate with Lamotrigine increases Lamotrigine concentrations, with an increased risk of serious skin reactions, including Stevens-Johnson syndrome.
Lamotrigine is primarily metabolised by glucuronidation via UGT2B7 (and UGT1A4). Valproate potently inhibits these enzymes, increasing lamotrigine half-life from 25 h to 60 h and doubling steady-state levels. The most serious risk is Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), especially when the initial dose is high or titration is rapid. The Portuguese Prontuário Terapêutico recommends: initial dose 12.5 mg/day (instead of 25 mg), increases of 25 mg every 2 weeks (instead of weekly), and immediate discontinuation at any skin rash. Monitor for skin rashes daily during the first 8 weeks.
Valproate doubles lamotrigine levels via UGT2B7 inhibition. Risk of SJS/TEN especially at high initial doses.
Valproate inhibits the glucuronidation of Lamotrigine, doubling its half-life and raising its concentrations; the risk of severe rash is highest in the first months.
Watch for rash, fever, lymphadenopathy or flu-like symptoms in the first 8 weeks.
Any rash or symptoms suggestive of a serious reaction require immediate discontinuation of Lamotrigine and medical evaluation.
Reduce the Lamotrigine dose (approximately half) when given with Valproate and increase it very gradually.
DailyMed/FDA (NIH/NLM) — approved Valproic acid label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a33f7657-ad0f-43e9-ba48-024746e6d08e ; approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Alcohol can increase lamotrigine metabolism (enzyme induction) and reduce anticonvulsant efficacy; acute intake also potentiates sedation.
Avoid alcohol; if unavoidable, keep intake stable.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733
Lamotrigine can be administered with or without food, with no relevant change in absorption.
Take at the same time every day, with or without food.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733
Lamotrigine can cause severe skin rash (SJS/TEN); the risk is higher with rapid titration and in susceptible patients.
Titrate slowly per protocol and stop at any skin rash.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733
Lamotrigine is eliminated renally; renal impairment reduces clearance and increases the risk of toxicity.
Reduce the maintenance dose in renal impairment and adjust in haemodialysis.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733
Lamotrigine monotherapy has a relatively low risk of malformations, but the risk increases with polytherapy (especially with valproate).
Maintain monotherapy at the lowest effective dose; do not stop without reassessing seizure risk.
Present in breast milk in relevant amounts; generally considered compatible, monitoring the infant.
No specific contraception required; lamotrigine does not reduce the efficacy of hormonal contraceptives.
DailyMed/FDA (NIH/NLM) — approved Lamotrigine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57f04b9b-06cd-8044-e063-6394a90ae733
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Anticonvulsant and mood-stabilising effect; efficacy in epilepsy was shown in preventing seizure spread (MES, pentylenetetrazol and kindling models). Does not inhibit NMDA-receptor-mediated activity. Inhibits dihydrofolate reductase in vitro (clinical relevance unknown).
The proposed mechanism involves inhibition of voltage-sensitive sodium channels, stabilising neuronal membranes and modulating presynaptic release of excitatory amino acids (glutamate and aspartate).
Rapid, almost complete oral absorption (absolute bioavailability 98%), without relevant first-pass effect and unaffected by food; peak plasma levels 1.4-4.8 hours after dosing. Volume of distribution 0.9-1.3 L/kg; protein binding ~55%.
Metabolised predominantly by glucuronic acid conjugation (main metabolite: inactive 2-N-glucuronide); self-induction of metabolism (~25% half-life reduction with multiple doses). Glucuronidation inducers (carbamazepine, phenytoin, phenobarbital, rifampin, oral contraceptives) accelerate elimination; valproate inhibits it (half-life ~59 h). 94% of the dose is recovered in urine.
Elimination half-life of about 25-33 hours in healthy adults without concomitant medication; ~14.4 hours with enzyme inducers and ~58.8 hours with valproate.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
