Lamotrigine | Epilepsy clinician handbook
- 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.
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.
- 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.
Interactions and precautions
Care must be taken when lamotrigine is combined with sodium valproate.
- There is a significant synergistic drug interaction with valproate (valproate is an enzyme inhibitor, lamotrigine clearance is reduced and thus lamotrigine levels are higher).
- This can increase risk of a serious rash significantly (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis).
- Lower doses of lamotrigine and slow escalation are required.
- Oral contraceptives and the other anti-seizure medications that induce hepatic glucuronidation will also decrease the level of lamotrigine.
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 may aggravate myoclonic seizures and syndromes with predominant myoclonic seizures.