Lamotrigine
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.
Lamotrigine can be used on its own or in combination with sodium valproate. When used in combination with Valproate, both the maximum doses of lamotrigine and valproate need to be adjusted.
The starting dose of lamotrigine is smaller and the dose is increased carefully and gradually.
Important: Dosing information
Initiation and escalation dosing on this webpage are a guide only.
All medications must be individualised based on:
- patient age, weight, co-morbidities
- disease, seizure type, frequency, duration
- medication metabolism, interactions, side-effect profile characteristics.
Further consultation with appropriate formularies or a paediatric neurologist may be required.
Dosing
Commonly used regime (not for patients on sodium valproate)
- If the patient is on sodium valproate, see: Lamotrigine and sodium valproate combination.
- 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).
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.
Formulary
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.
No drug level monitoring is currently available and no routine blood tests are required.
Lamotrigine may aggravate myoclonic seizures and syndromes with predominant myoclonic seizures.
Resources
This information is reviewed annually by the Sydney Children’s Hospitals Network Paediatric Epilepsy NSW working group which includes medical, nursing, and pharmacy representation.