Lamotrigine and Valproate combination

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.