Lamotrigine, a phenyltriazine compound, is an antiepileptic used mainly for monotherapy or adjunctive treatment of partial seizures and primary and secondarily generalised tonic-clonic seizures. It may be used for seizures associated with the Lennox-Gastaut syndrome and for the maintenance treatment of bipolar disorder. The doses given below for the use of lamotrigine in epilepsy are those licensed in the UK; similar doses are given in the United States of America (US and USA) although the use of lamotrigine is more limited than in the UK.
- The initial oral dose for use as monotherapy is 25 mg once daily for 2 weeks followed by 50 mg once daily for 2 weeks; thereafter the dose is increased by a maximum of 50 to 100 mg every 1 to 2 weeks to usual maintenance doses of 100 to 200 mg daily, given as a single dose or in 2 divided doses. Some patients have required up to 500 mg daily
- The initial oral dose of lamotrigine for use as an adjunct to therapy with enzyme-inducing antiepileptics (but not with valproate) is 50 mg once daily for 2 weeks followed by 50 mg twice daily for 2 weeks; thereafter the dose is increased by a maximum of 100 mg every 1 to 2 weeks to usual maintenance doses of 200 to 400 mg daily given in 2 divided doses. Some patients have required up to 700 mg daily
- In those taking valproate the initial oral dose of lamotrigine is 25 mg every other day for 2 weeks followed by 25 mg once daily for 2 weeks; thereafter the dose is increased by a maximum of 25 to 50 mg every 1 to 2 weeks to usual maintenance doses of 100 to 200 mg daily given as a single dose or in 2 divided doses
- In those taking oxcarbazepine but no enzyme-inducing or -inhibiting antiepileptics the dosage regimen of adjunctive lamotrigine is as for monotherapy
If the potential for interaction with adjunctive antiepileptics is unknown, treatment with lamotrigine should be started with lower doses such as those used with valproate. For comment on the need to modify maintenance doses when starting or stopping oral contraceptives see Sex Hormones, under Interactions, above.
For doses in children, see below. In the management of bipolar disorder, the target dose of lamotrigine is 200 mg daily as monotherapy; for patients taking valproate the target dose is 100 mg daily and in those taking enzyme-inducing drugs (but not with valproate) the target dose is 400 mg daily. Lamotrigine should be started at a reduced dose and increased gradually to the target dose in a regimen similar to that used in the treatment of epilepsy.
Doses should be reduced in patients with hepatic impairment regardless of indication.
As with other antiepileptics, withdrawal of lamotrigine therapy or transition to or from another type of antiepileptic therapy should be made gradually to avoid precipitating an increase in the frequency of seizures. For a discussion on whether or not to withdraw antiepileptic therapy in seizure-free patients. Licensed drug information recommends that regardless of indication the withdrawal of lamotrigine should be tapered over at least 2 weeks.
Administration in children. Lamotrigine is used as an adjunct in the treatment of partial seizures and primary and secondarily generalised tonic-clonic seizures in children aged 2 years and over; it is used as monotherapy in those over 12 years of age. Lamotrigine may also be used for seizures associated with the Lennox-Gastaut syndrome.
The doses given below are those licensed in the UK; similar doses are given in the United States of America (US and USA) although the use of lamotrigine is more limited than in the UK.
- In those taking enzyme-inducing antiepileptics (but not with valproate) the initial oral dose of lamotrigine is 600 micrograms/kg daily in 2 divided doses for 2 weeks followed by 1.2 mg/kg daily for 2 weeks; thereafter the dose is increased by a maximum of 1.2 mg/kg every 1 to 2 weeks to usual maintenance doses of 5 to 15 mg/kg daily given in 2 divided doses
- In those taking valproate the initial oral dose of lamotrigine is 150 micrograms/kg once daily for 2 weeks followed by 300 micrograms/kg once daily for 2 weeks; thereafter the dose is increased by a maximum of 300 micrograms/kg every 1 to 2 weeks to usual maintenance doses of 1 to 5 mg/kg daily, given as a single dose or in 2 divided doses
- In those taking oxcarbazepine but no enzyme-inducing or -inhibiting antiepileptics the initial oral dose of lamotrigine, given as a single dose or in 2 divided doses, is 300 micrograms/kg daily for 2 weeks, followed by 600 micrograms/kg daily for 2 weeks; thereafter the dose is increased by a maximum of 600 micrograms/kg every 1 to 2 weeks to usual maintenance doses of 1 to 10 mg/kg daily, to a maximum of 200 mg daily.
If the calculated daily dose of lamotrigine lies between 1 and 2 mg, then 2 mg may be given on alternate days for the first 2 weeks of therapy. Lamotrigine should not be given if the calculated daily dose is less than 1 mg.
Children over 12 years of age may be given the adult dosage regimen for monotherapy and adjunctive therapy.
Administration in hepatic impairment. UK licensed product information for lamotrigine recommends that doses should be reduced by about 50% in patients with moderate hepatic impairment (Child-Pugh category B), and by about 75% in severe impairment (Child-Pugh category C). US licensed product information recommends that doses should be reduced by about 25% in patients with moderate to severe hepatic impairment without ascites, and by about 50% in those with severe hepatic impairment with ascites.
Anxiety disorders. Small studies have suggested that lamotrigine may relieve some of the symptoms of post-traumatic stress disorder.
Bipolar disorder. In a multicentre placebo-controlled study involving 195 patients, lamotrigine 50 or 200 mg daily by mouth produced dose-related improvement in patients with bipolar disorder experiencing a major depressive episode. Further data from randomised controlled studies have confirmed benefit for depressive symptoms (although not for mania), and reviews have generally favoured its use, although some have queried the strength of the evidence. Guidelines for the treatment of bipolar disorder now recommend lamotrigine as a first-line option for bipolar depression, and it is licensed for such use in a number of countries (see also Uses and Administration, above).
Epilepsy. Lamotrigine is used in the treatment of epilepsy (). It is used in partial seizures with or without secondary generalisation, and in generalised tonic-clonic seizures, although valproate is the drug of choice in the latter where these are associated with the syndrome of primary generalised epilepsy. It is also recommended in absence seizures, although the evidence base is not particularly strong, and may be used in juvenile myo-clonic epilepsy and tried in tonic or atonic seizures. As monotherapy for partial seizures with or without secondary generalisation, lamotrigine was found to be better than carbamazepine (the established first-line drug) in terms of time to treatment failure and tolerability. In patients with newly-diagnosed partial seizures with or without secondary generalisation, lamotrigine had a similar efficacy to carbamazepine, but again was better tolerated. A systematic review of randomised, placebo-controlled studies concluded that lamotrigine is also effective in reducing the seizure frequency when added to current antiepileptic regimens in patients with refractory partial seizures. As monotherapy for primary generalised and unclassifiable seizures lamotrigine was found to be significantly inferior to valproate (the established first-line drug) in terms of seizure control, with almost twice the failure rate; valproate was also significantly more effective for achieving 12-month remission and prolonging the time to first seizure. Benefit was seen with adjunctive lamotrigine when compared with placebo in children and adults for treatment-resistant primary generalised seizures; it was also suggested that lamotrigine therapy may be appropriate when determination of the type of epilepsy in these patients is not possible.
Lamotrigine appears to be an effective adjunctive treatment in children with the Lennox-Gastaut syndrome. It has also been found to be effective and well tolerated as adjunctive therapy in paediatric patients with refractory epilepsy including those with developmental impairment; it was particularly effective in absence and atypical seizures in this open-label study. (Evidence for the use of lamotrigine to treat absence seizures, as for the other common alternatives ethosuximide and valproate, is, however, generally poor.)
Migraine. Case reports and open studies have suggested that lamotrigine may be of benefit in the prophylaxis of migraine aura.
Motor neurone disease. Lamotrigine has been tried as a potential therapy for amyotrophic lateral sclerosis (see Motor Neurone Disease) but with disappointing results.
Movement disorders. Symptomatic improvement and a trend towards decreased chorea was reported with lamotrigine in a double-blind, placebo-controlled study of 64 patients with Huntington’s chorea () with motor signs of less than 5 years’ duration. There was, however, no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months.
Neuropathic pain. There is growing evidence that lamotrigine is of use in the management of neuropathic pain. It was effective when used with carbamazepine or phenytoin in the treatment of refractory trigeminal neuralgia, and has also shown promise in the treatment of pain associated with HIV-related distal sensory neuropathy (). Some benefit has been found in the treatment of diabetic neuropathy (). Case reports and a placebo-controlled trial have also indicated that lamotrigine may be effective in central post-stroke pain (). More recently, the use of lamotrigine in neuropathic pain has been reviewed. Based on the same studies, one review concluded that lamotrigine is an effective treatment for various types of neuropathic pain and that further studies are warranted while another concluded that it is unlikely to be of benefit and that further studies are probably not justified.
Schizophrenia. Lamotrigine has been tried as adjunctive therapy in treatment-resistant schizophrenic patients and a benefit has been reported in few studies, although patient numbers have been small. However, a systematic review of the use of lamotrigine in schizophrenia concluded that the evidence for its use was poor, although it was suggestive of a positive effect on symptoms.
International Brand Drug Names
The information about drugs (tablets, pills, capsules, creams, solution, nasal spray, inhaler) around the world.
Argentina: Dafex; Epilepax; Lagotran; Lamictal; Lamirax; Lamotril; Latrigin;
Australia: Elmendos; Lamictal; Lamidus; Lamitrin; Lamogine; Seaze;
Austria: Bipolam; Gerolamic; Lamictal; Lamotriglax;
Belgium: Lambipol; Lamictal;
Brazil: Lamictal; Lamitor; Neural; Neurium;
Chile: Daksol; Lafigin; Lamictal; Lomarin; Meganox; Tradox; Trizol;
Czech Republic: Danoptin; Epimil; Epiral; Lameton; Lamictal; Lamiger; Lamogine; Lamolep; Lamotax; Lamotri; Lamotrix; Latrigil; Plexxo; Rubimar; Triginet;
France: Lamicstart; Lamictal;
Germany: Elmendos; Lamictal; Lamo; Lamotriax; Lamotrig;
Greece: Lamictal; Lamotrix;
Hong Kong: Lamictal;
Hungary: Epitrigine; Lamictal; Lamitrin; Lamolep; Plexxo;
India: Lamepil; Lametec;
Ireland: Lamictal; Larig;
Israel: Lamictal; Lamodex; Lamogine;
Malaysia: Lamictal; Lamotrix;
Mexico: Lamdra; Lamictal; Limatic; Protalgine;
Netherlands or Holland: Lamictal; Lamitor; Lamochem; Lamomont; Lamotifi; Plexxo; Symla;
New Zealand: Lamictal; Mogine;
Poland: Danoptin; Epilactal; Lamia; Lamilept; Lamitrin; Lamotrihexal; Lamotrix; Plexxo; Triginet;
Russia: Convulsan (Конвульсан); Lamictal (Ламиктал); Lamitor (Ламитор); Lamolep (Ламолеп);
South Africa: Epitec; Lamictin; Lamitor;
Spain: Crisomet; Labileno; Lamictal;
UK or Britain: Lamictal;
US or USA: Epitrogine; Lamictal;
Venezuela: Epifon; Lamictal.
Selections from the book: “Martindale: The Complete Drug Reference. Thirty-sixth edition”. Pharmaceutical Press. 2009
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