Algorithm for Adding Valproate to Lamotrigine

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 seizures Addition of valproate will increase lamotrigine levels. Obtain baseline lamotrigine plasma concentration prior to starting VPA

Initiate dose at 15mg/kg/day in divided doses Valproate (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 doing well Patient not Patient no adverse events/ on drug/few or no seizures doing well on drug seizures not controlled

Titrate VPA to chosen Adverse Adverse maintenance dose events/no seizures events/no seizures Maintain lamotrigine or continue to titrate to reduce lamotrigine maintenance dose by 25% each week to DC. Reduce (up to 60mg/kg/day) May reduce slower to Reduce lamotrigine dose meet patient needs lamotrigine dose 25% Increase VPA dose to tolerated conc.

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

Continued adverse events/seizures Continued adverse events Change dosage form or schedule VPA Reduce lamotrigine 25% each week Continue to control for adverse effects Reduce lamotrigine dose/Increase VPA

Patient doing well* Patient not doing well Patient doing well

Adverse Events/Seizures Adverse Events/No seizures Seizures/no adverse events reduce/DC lamotrigine dose reduce/DC lamotrigine dose Increase Dose VPA Increase dosage VPA Modify dosage form VPA Modify schedule VPA Modify schedule VPA

* 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