Lamotrigine

Lamotrigine is an antiepileptic used, as sole treatment or in combination with other antiepileptic drugs, for partial seizures and primary and secondarily generalised tonic-clonic seizures. It is also used for myoclonic seizures and may be tried for atypical absence, atonic, and tonic seizures in the Lennox-Gastaut syndrome. Lamotrigine may cause serious skin rash especially in children. Lamotrigine has similar efficacy and better tolerability to carbamazepine.

• Lamotrigine is now licensed in the UK for monotherapy use in adults and in children over 12 years.¹
  Lamotrigine is a first-line drug for patients with partial seizures and with generalised seizures.
• It is also used for seizures associated with Lennox-Gastaut syndrome
• Trigeminal neuralgia (unlicensed indication)
• Lamotrigine (in combination with an antidepressant) is indicated for the treatment of acute bipolar depression in patients with a history of mania. It is also indicated for prophylactic treatment of bipolar disorder in those for whom depressive relapse is a greater problem (less effective in treatment and prevention of mania)²

• Closely monitor (including hepatic, renal and clotting function tests)
• Consider withdrawal if rash, fever, influenza-like symptoms, drowsiness, or worsening of seizure control develops. Lamotrigine given with other antiepileptics has been associated with a rapidly progressive illness with status epilepticus, multi-organ dysfunction, disseminated intravascular coagulation and death
• Avoid abrupt withdrawal (taper off over 2 weeks or longer) unless serious skin reaction occurs
• Hepatic impairment (reduce dose)
• Renal impairment (active metabolite may accumulate)
• Elderly
• Pregnancy (benefit of treatment outweighs risk to the fetus)
• Monitor body-weight in children and review dose if necessary
• Blood disorders: the CSM has advised prescribers to be alert for symptoms and signs suggestive of bone-marrow failure such as anaemia, bruising, or infection. Aplastic anaemia, bone-marrow depression and pancytopenia have been associated rarely with lamotrigine
• Warn patients to see their doctor immediately if rash or influenza-like symptoms associated with hypersensitivity develop

Avoid the following if possible, or monitor frequently.

• Lamotrigine does not seem to interact with other antiepileptic drugs, although it may increase levels the active metabolite of carbamazepine
• Hepatic enzyme inducers increase lamotrigine clearance, reducing its half-life. Therefore higher doses of lamotrigine need to be used with concomitant enzyme inducing drugs such as phenytoin and carbamazepine
• Inhibitors of hepatic enzymes, such as sodium valproate, block the metabolism of lamotrigine so that reduced doses of lamotrigine have to be used if both drugs are given together
• Patients taking a combination of an enzyme-inducing antiepileptic drug and sodium valproate will exhibit intermediate half-life values
• The tolerability to any particular lamotrigine level may be reduced when patients are also taking carbamazepine

• Headaches, ataxia, diplopia, insomnia, nausea, dizziness, fever, malaise, influenza-like symptoms and drowsiness are the most commonly reported acute adverse effects of lamotrigine, particularly during dose escalation
• A skin rash is the commonest idiosyncratic side effect of this drug and affects up to 5% of patients. The incidence is higher in combination with sodium valproate or if larger initial doses of lamotrigine are used
• Serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (rarely with fatalities) have developed especially in children. Most rashes occur in the first 8 weeks. The CSM has advised that factors associated with increased risk of serious skin reactions include concomitant use of valproate, initial lamotrigine dosing higher than recommended and more rapid dose escalation than recommended

More rarely reported adverse effects include:

• Hepatic dysfunction, lymphadenopathy, leucopenia, and thrombocytopenia
• Rash, angioedema, and photosensitivity
• Diplopia, blurred vision, conjunctivitis
• Irritability, aggression, tremor, agitation, confusion

• The recommended starting dose is 25 mg. This dose is given on alternate days in patients receiving concomitant sodium valproate and daily as monotherapy or in patients receiving other antiepileptic drugs
• The maximum recommended dose is 400-500 mg/day in two divided doses
• Treatment should be slowly titrated upwards over a period of several weeks as too rapid titration may be associated with an increased incidence of adverse events, particularly skin rash

• Lamotrigine blood levels increase linearly with increasing dosage. There is a large inter-patient variability in blood levels at which an optimum response is achieved. Different lamotrigine dosages are required depending on interacting co-medication with other antiepileptic drugs
• The target range for lamotrigine is 4-16 mcmol/L
• There is good correlation between plasma and saliva concentrations