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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 seizureo Lennox-Gastaut syndrome,
o Because of serious potential toxicity, felbamate should be
reserved for rare, compassionate use byphysicians 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 recommendedo 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 ofseizures. 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 Children
Monotherapy:
Begin with 1,200 mg daily, given in 3/4devideddose..
Increase by 600 mg/2 weeks to a total daily dosageof 2,400 to
3,600 mg.
Adjunctive therapy:If taking phenytoin,Valp or CBZ , a 20 to
35percent dose reduction necessary.
LGS,2-15years-is 15 mg per kg, given in three tofour divided
doses.
Dosages of other antiepileptic drugs should bereduced by 20
percent, with further reductions
based on side effects or drug levels.
The daily dosage should increase by 15 mg per kgweekly, to a
maximum of 45 mg per kg.
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Retigabineor ezogabine
o Used as a treatment for partial epilepsies.o Developed by
Valeant Pharmaceuticals and GlaxoSmithKline.o Approval
European Medicines Agency-trade name Trobalt-on March 28, 2011
US FDA - trade name Potiga - on June 10, 2010.
o MOA: otassium channel opener. Voltage gated. In brain.o 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 andepilepsy used: retigabine
suppresses seizures induced by electroshock, electrical kindling of
theamygdala,pentylenetetrazol, kainate, NMDA, and picrotoxin.
o Clinical trialso 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 otherantiepileptic 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 totreatment.
o Regulatory approvalo 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-ontreatment of partial
seizures in adults).
o However, the possibility of urinary retention as an adverse
effect was considered a significant concern, andthe panel's members
recommended that some sort of monitoring strategy be used to
identify patients at riskof bladder dysfunction.
o Potiga was approved by the FDA on June 10, 2010, and is set to
become available on the U.S. marketafterscheduling by the Drug
Enforcement Administration.
o Adverse effectso 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 thefirst 2 months of
treatment
StiripentolMOA
Increases GABA transmission.
HistoryIn 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 myoclonicepilepsy in infancy
(SMEI)In addition, it may be used to treat refractory childhood
epilepsy in conjunction with carbamazepine. It appears to beless
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%
