Overview
- 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.
Dosage
- 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.
A reasonable dosage regime for 2-12 year-olds is the commencement of lamotrigine 0.15mg/kg/second-daily (for a week), then 0.15mg/kg/daily (for 2 weeks). One can continue with an escalation of 0.15mg/kg/day each two weeks to the target dose. If the patient is tolerating the combination therapy, the lamotrigine titration dosage could be increased with careful monitoring (particularly looking for rash - see precautions tab) to 0.3mg/kg/day during the latter part of the escalation phase. The maintenance dose is 1-4mg/kg/day. Maximum dose is 5mg/kg/day given as a single dose or two equally divided doses. The maximum dose of lamotrigine with valproate in this age group is generally not above 200mg/day. Dosages per kilogram can only be used up to weights of 30-40kgs.
- Adding lamotrigine to valproate does not appear to affect valproate levels.
- On lamotrigine, a recommended maximum dose of valproate is approximately 30mg/kg.
- All anticonvulsants are potentially teratogenic and this is often dose-related (see section: AED Prescribing - Pregnancy)
- For a complete list of adverse effects, appropriate formularies should be consulted.
Interactions | Precautions
- Oral contraceptives and the other anticonvulsants that induce hepatic glucuronidation will also decrease the level of lamotrigine.
- 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.
Information last reviewed: 5/05/2023.