Lamotrigine

Usage

  • Lamotrigine is most commonly used in generalised epilepsies.
  • It has also been shown to be efficacious in focal seizure disorders.
  • The PBS indication is for epileptic seizures with the following clinical criteria:
    • The condition must have failed to be controlled satisfactorily by other anti-epileptic drugs; OR

    • Patient must be a woman of childbearing potential.

  • Care must be taken when combined with valproate (see later section).
  • Lamotrigine was found to be less efficacious than sodium valproate and ethosuximide in Childhood Absence Epilepsy. 1

 Resources

  • 1Tracy A. Glauser et al. Ethosuximide, Valproic Acid, and Lamotrigine in Childhood Absence Epilepsy. N Engl J Med 2010; 362:790-799

Side effects

Possible side effects:

  • Rash is the most serious side effect to monitor. Steven Johnson Syndrome has a higher risk of occurring in children than adults on lamotrigine. Co-treatment with sodium valproate is a significant risk factor (see section: lamotrigine and valproate combination). Previous skin reaction to another anticonvulsant also increases the risk. Starting at low dose and increasing very slowly decreases risk. Development of rash while on lamotrigine warrants urgent medical review. Red flags are new onset conjunctivitis, mucosal peeling, and systemic signs.
  • It is thought to be safer in pregnancy compared to sodium valproate; however there is still risk of teratogenicity. Pregnancy must be carefully monitored by a neurologist as drug levels change (see section: AED Prescribing - Pregnancy).
  • Patients often feel better on lamotrigine as it is a mood stabiliser.
  • Insomnia may occur and it is sometimes helpful to give the dosage early in the day.
  • Uncommon side effects include liver and haematological abnormalities.
  • Rarely ataxia or drowsiness are noted.

For a complete list of adverse effects, appropriate formularies should be consulted.

Dosing

  • The below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Commonly used regime (***not for patients on sodium valproate)

  • Patient <12 years of age: 4-5mg/kg/day is a low target dose. Higher doses up to approximately 8mg/kg/day monotherapy can be used. Lamotrigine can be given in 1 or 2 daily doses. In higher doses, consultation with a Paediatric Neurologist may be helpful.
  • Weeks 1-2: 0.3 mg/kg/day in 1-2 divided doses.
  • Weeks 3-4: 0.5 mg/kg/day in 1-2 divided doses. Can continue this regime to the target dose. Slow escalation is mandatory.   
  • Dosages per kilogram can only be used up to weights of 30-40kgs.
  • For children <24 months: initial doses may need to be administered every other day due to limited strengths of available products.
  • Adult patients: Recommended adult maintenance dosage: 200mg-400mg (particularly if on enzyme inducer).
  • ***If the patient is on sodium valproate, see section: Lamotrigine and sodium valproate combination.

Preparation

  • Tablets 5mg, 25mg, 50mg, 100mg, 200mg.
  • No syrup form.

Monitoring

  • No drug level monitoring is currently available and no routine blood tests are required.

Interactions | Precautions

Care must be taken when lamotrigine is combined with sodium valproate.

Cardiac Safety Warning

A joint Task Force of the International League Against Epilepsy (ILAE) and the American Epilepsy Society (AES) has published an advisory on lamotrigine use, following a recent cardiac safety warning issued by the US Food and Drug Administration (FDA) (26 January 2021).

  • The FDA has added a caution for use of lamotrigine in patients with an underlying cardiac or rhythm problem (Brugada Syndrome and other sodium channelopathies), cardiac disease or cardiac abnormality.
  • You can access the advisory via this link:  Lamotrigine advisory (see section 2)

Lamotrigine may aggravate myoclonic seizures and syndromes with predominant myoclonic seizures.

 

Information last reviewed: 24/04/2023.