EPILEPSY Update

AED Classification (Accrding to MOA) (Most conceptual)

Drug Chronology

New Drugs Under Trial

Classification as Old and New

EPILESY SYNDROMES

Mechanism of Action

Indication: AWSUM!!

Common Side Effects

Brivaracetam
4-n-propyl analogue of levetiracetam. Act by binding to the ubiquitous synaptic vesicle protein SV2. Phase II clinical trials in adult patients with refractory partial seizures were promising. Positive preliminary results from stage III trials have been recorded. 10 times more potent in mouse models than levetiracetam.

Felbamate
o Indication: o partial seizure o Lennox-Gastaut syndrome, o Because of serious potential toxicity, felbamate should be reserved for rare, compassionate use by physicians experienced in treating patients with epilepsy that is difficult to control. o Absorbed well orally with bioavailability greater than 90 percent. o The addition of phenytoin or carbamazepine reduces felbamate levels by 40 percent Category C Found in breast milk, breast feeding is not recommended o Pediatric use is approved only for adjunctive therapy in LGS. o Serious side effects appeared: Aplastic anemia and hepatic failure. Aplastic anemia: o 100 times greater risk than it is in the general population. One in every 3,600 to 5,000 patients.. o The fatality rate 30 percent. o Check for signs of infection, bleeding and easy bruising, or symptoms of anemia such as fatigue or weakness. Hepatotoxicity o one in every 24,000 to 34,000 pt. o Need for monitoring drug levels has not been established. o Base line:CBC,. Liver enzyme levels should be determined every one to two weeks,.Discontinue if the AST/ALT or bilirubin levels increase above baseline. o Because of serious side effects, felbamate is not recommended as first-line therapy in the treatment of seizures. The manufacturer recommends its use only in patients who do not adequately respond to alternative therapy and whose epilepsy is so severe that the substantial risks of aplastic anemia and hepatic failure are deemed acceptable. o Dosage:

Adult Monotherapy: Begin with 1,200 mg daily, given in 3/4devided dose.. Increase by 600 mg/2 weeks to a total daily dosage of 2,400 to 3,600 mg. Adjunctive therapy: If taking phenytoin,Valp or CBZ , a 20 to 35 percent dose reduction necessary.

Children LGS,2-15years-is 15 mg per kg, given in three to four divided doses. Dosages of other antiepileptic drugs should be reduced by 20 percent, with further reductions based on side effects or drug levels. The daily dosage should increase by 15 mg per kg weekly, to a maximum of 45 mg per kg.

Retigabine or ezogabine
o o o Used as a treatment for partial epilepsies. Developed by Valeant Pharmaceuticals and GlaxoSmithKline. Approval European Medicines Agency-trade name Trobalt-on March 28, 2011 US FDA - trade name Potiga - on June 10, 2010. MOA: otassium channel opener. Voltage gated. In brain. Among the newer anticonvulsants, retigabine was one of the most widely studied in the preclinical setting: it was the subject of over 100 published studies before clinical trials began. In preclinical tests, it was found to have a very broad spectrum of activitybeing effective in nearly all the animal models of seizures and epilepsy used: retigabine suppresses seizures induced by electroshock, electrical kindling of the amygdala,pentylenetetrazol, kainate, NMDA, and picrotoxin. Clinical trials o In a double-blind, randomized, placebo-controlled Phase II clinical trial, retigabine was added to the treatment regimen of 399 participants with partial seizures that were refractory to therapy with other antiepileptic drugs. The frequency with which seizures occurred was significantly reduced (by 23 to 35%) in participants receiving retigabine, and approximately one fourth to one third of participants had their seizure frequency reduced by more than 50%. Higher doses were associated with a greater response to treatment. Regulatory approval o The U.S. Food and Drug Administration accepted Valeant's New Drug Application for retigabine on December 30, 2009. o The FDA Peripheral and Central Nervous System Drugs Advisory Committee met on August 11, 2010 to discuss the process and unanimously recommended approval of Potiga for the intended indication (add-on treatment of partial seizures in adults). o However, the possibility of urinary retention as an adverse effect was considered a significant concern, and the panel's members recommended that some sort of monitoring strategy be used to identify patients at risk of bladder dysfunction. o Potiga was approved by the FDA on June 10, 2010, and is set to become available on the U.S. market afterscheduling by the Drug Enforcement Administration. Adverse effects o CNS:drowsiness, dizziness andvertigo, confusion, and slurred speech. o In 2013 FDA warned that, Potiga (Ezogabine) can cause blue skin discoloration and eye abnormalities characterized by pigment changes in the retina. o Psychiatric symptoms and difficulty urinating have also been reported, with most cases occurring in the first 2 months of treatment

o o

Stiripentol
MOA Increases GABA transmission. History In December 2001 EMA granted stiripentol orphan drug status for the treatment of severe myoclonic epilepsy in infancy (SMEI, also known as Dravet's syndrome). 2007, the EMA granted the drug a marketing authorisation that is valid throughout the European Union. Indications and usage It is indicated as an adjunctive therapy with sodium valproate and clobazam for treating severe myoclonic epilepsy in infancy (SMEI) In addition, it may be used to treat refractory childhood epilepsy in conjunction with carbamazepine. It appears to be less effective in adolescents and adults. Dosing Initial dose is 50 mg/kg per day. This may be increased up to 100 mg/kg per day, with a maximum of 4g. The dose to be divided into two or three with meals. The dose of other anticonvulsants may have to be reduced (possibly up to 50%