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 rash significantly.
  • Lower doses of lamotrigine and slow escalation are required.

Dosage

A reasonable dosage regime is commencement of lamotrigine 0.15mg/kg/second daily (for a week), then same dose daily (for 2 weeks), then increase every 2 weeks by 0.15mg/kg/day to target 1-3mg/kg/day.  Maximal dose 4-5mg/kg/day. 

  • Adding lamotrigine to valproate does not appear to affect valproate levels.
  • On lamotrigine, a recommended maximum dose of valproate is approximately 30mg/kg.
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs. Consult appropriate formularies for higher weights and in the adult range.
  • These dosages are only a guideline and appropriate formularies should be consulted as needed.
  • 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.