Add on Valproate to Lamotrigine Algorithm for Treating Patients with Epilepsy*

Patient presents with Seizures has Partial or Primary Generalized Epilepsy (simple partial, complex partial, primary or secondarily generalized tonic clonic, absence, juvenile myoclonic, atonic, etc)

Has been treated with lamotrigine to a level which caused adverse effects with some or no control of seizuresAddition of valproate will increase lamotrigine levels.

Obtain baseline lamotrigine plasma concentration prior to starting VPA

Initiate dose at 15mg/kg/day in divided dosesValproate (sodium valproate, divalproex sodium )

(Depakene(valproic acid), Depakote/Depakote ER, Depakote Sprinkles, Depakote liquid)

Reduce lamotrigine dose by 50% when initiate VPA if patient was on maximum tolerated dose.

Increase valproate (VPA) by 250-500 mg/day per week to an initial maintenance dose of ~ 40-60mg/kg/day(target concentration 50-100mcg/ml –this is not an absolute number)

Inhibits the cytochrome P-450 enzymes and monitoring of concomitant drug therapy is advised. Subsequent reductions in lamotrigine dose may be needed

Patient returns to clinic in 2-4 weeks to monitor for efficacy, side effects. (see drug information for common adverse effects)

Return based on frequency of seizures.Drug level monitoring required if adverse events or efficacy/compliance in question

Patient not doing well on drug

Patient doing well on drug/few or no seizures

Patient no adverse events/seizures not controlled

continue to titrate to maintenance dose

(up to 60mg/kg/day)

Titrate VPA to chosen maintenance dose

Maintain lamotrigine or reduce lamotrigine

by 25% each week to DC.May reduce slower to

meet patient needs

Patient returns to clinic(4-8 weeks depending frequency)

Patient returns to clinic(4-8 weeks depending frequency)

Patient doing well* Patient doing wellPatient not doing well

Adverse Events/No seizuresreduce/DC lamotrigine dose

Modify dosage form VPAModify schedule VPA

Adverse Events/Seizuresreduce/DC lamotrigine dose

Increase dosage VPAModify schedule VPA

Seizures/no adverse eventsIncrease Dose VPA

Reduce lamotrigine dose 25%

Reduce lamotrigine dose

Increase VPA dose to tolerated conc.

Continued adverse events/seizuresChange dosage form or schedule VPAContinue to control for adverse effects

Reduce lamotrigine dose/Increase VPA

Continued adverse eventsReduce lamotrigine 25% each week

Adverse events/no seizures

Adverse events/no seizures

* When changing to Depakote ER follow package insert guidelines, increase dose by 8-20% over Depakote maintenance dose.Indications for Valproate (Depakote, valproic acid) http://www.epilepsy.com/medications/valproic-acid, http://epilepsy.com/medications/divalproex-sodium Developed for Epilepsy.com by Ruth Nemire, Pharm D, Nova Southeastern University College of Pharmacy