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Side effects include dizziness, drowsiness, headaches, hyporexia, nausea and vomiting,
weight loss, skin rashes, irritability, impaired concentration and fatigue. These are mostly
transient and seem to be related to the dose and rate of titration. Nephrolithiasis has also been
reported, particularly in Caucasians and people starting it should increase their fluid intake to
reduce this risk. It is not recommended for women of child-bearing age as there are issues
about its teratogenic potential.

AEDs marketed elsewhere

Felbamate
Felbamate is a di-carbamate closely related to meprobamate. Its exact mechanism of action
is not known but it appears to reduce seizures both by increasing seizure threshold and by
inhibiting seizure spread.

It is a drug with a broad spectrum of action but due to its safety profile it is used as a drug of
last resort in people with intractable epilepsy, particularly in those within the Lennox-Gastaut
spectrum. The usual dose is between 2400 and 4800 mg/day. The recommended starting dose
for most people is 400 mg once daily, titrating upwards every week in 400 mg/day increments
up to 2400 mg/day in two or three divided doses. After that the dose can be increased by 600
mg/day each week until seizure control is achieved or side effects develop.

Felbamate exhibits significant pharmacokinetic interactions with phenytoin, carbamazepine
and valproic acid: plasma phenytoin concentrations rise by 20% upon introduction of
felbamate; plasma carbamazepine concentrations are reduced by 2025% but there is a
concurrent increase in the concentrations of 10,11-epoxi-carbazepine, a metabolite of
carbamazepine; plasma valproate concentrations increase by about 50% during co-
medication with felbamate. The exact mechanism of these pharmacokinetic interactions is
unknown but their magnitude requires dosage adjustments. Felbamate metabolism is also
inducible by carbamazepine and phenytoin, and higher doses of felbamate may be necessary
during co-administration with these AEDs.

The most frequently reported side effects during felbamate therapy have been neurological
(diplopia, insomnia, dizziness, headache and ataxia), and gastrointestinal (anorexia, nausea
and vomiting). A major use-limiting problem is its potential to cause aplastic anaemia and
liver failure, affecting as many as one in 3000 people exposed to the drug. Hence, it seems
prudent to limit its use to severe intractable cases where potential benefit outweighs the risk.

Antiepileptic drugs currently in development

At present there are not many potential antiepileptic compounds undergoing clinical
evaluation and there is only one, brivitiracetam which is in the final stages of development.