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New Add-on Therapy for Partial-onset Epilepsy
Table 2: Adverse Effects of Antiepileptic Medications
Medication Common Adverse Events Serious Adverse Events
Felbamate Aplastic anemia, hepatic failure.
Topiramate Adult: Extremity paresthesia, weight loss, cognitive slowing, Renal calculi. Rarely: acute myopia in closed-angle glaucoma.
ataxia, dizziness, fatigue, somnolence, depression, and agitation.
Pediatric: fatigue, somnolence, anorexia, and anxiety.
Oxcarbamazepine Headache, weight gain, somnolence, dizziness, rash, hyponatremia,
alopecia, gastrointestinal upset, allergic rash.
Hyponatremia (uncommon in patients <17 years of age but
reported in 2.5% of adults and 7.4% of elderly people).
Exacerbation of seizures in juvenile idiopathic generalized epilepsies.
Lamotrigine Ataxia, diplopia, headache, tremor, blood dyscrasias, gastrointestinal Rash often associated with rapid titration. Severe rash, more common in
upset, psychosis, somnolence, insomnia and hypersensitivity reactions. children on valproate, may lead to rare but potentially-fatal Stevens-Johnson
Exacerbation of seizures in juvenile myoclonic epilepsy syndrome (0.1%).
Zonisamide Somnolence, fatigue, headache, weight gain, dizziness, anorexia, ataxia, Spontaneous abortions/ congenital abnormalities rate of 7%,
tremor, confusion, speech abnormalities, mental slowing, and irritability ~2x that of general population.
Renal calculi in 1.5% of patients, oligohidrosis in some children.
Allergic reactions in patients with sensitivity to sulfonamides.
Tigabine Diarrhea, somnolence, asthenia, depressed mood, emotional lability, Reports of convulsive and nonconvulsive status epilepticus with tigabine—
nervousness, tremor, dizziness, ataxia, abnormal thinking, abdominal pain, use with caution in a patient with a history of status epilepticus.
pharyngitis, confusion, psychosis, and skin rash. Contraindicated in absence or partial epilepsies with generalized spike
Children have a reduced clearance of tigabine. wave on electrocardiogram and in severe hepatic impairment,
pregnancy, and lactation.
Gabapentin Somnolence, ataxia, dizziness, nystagmus, tremor, fatigue, diplopia, rhinitis,
headache, nausea, or vomiting. Rash in 0.5%, neutropenia in 0.2%.
Levetiracetam Headache, accidental injury, convulsion, infection, asthenia, somnolence,
dizziness, pain, pharyngitis, and flu-like syndrome.
Pregabalin Dizziness, somnolence, ataxia, weight gain. May increase creatinine kinase,
decrease platelet count and increase PR interval.
once-daily administration and lack of drug interactions with other AEDs. There have been reports of both convulsive and non-convulsive status
The half-life of zonisamide may be decreased from 63 to 27–46 hours epilepticus with tigabine usage, and therefore it should be used
when co-administered with pheytoin, carbamazepine, phenobarbital, with caution in a patient with a history of status epilepticus. It is
or valproic acid, although zonisamide has no effect on the levels of contraindicated in absence epilepsy and in partial epilepsies with generalized
these medications.
10,19
spike wave on electrocardiogram (EEG), where it may worsen seizure control.
21
Although generally well-tolerated, the most commonly reported adverse Gabapentin
reactions with zonisamide were somnolence, fatigue, headache, weight Gabapentin is approved for the treatment of partial and secondarily
gain, dizziness, anorexia, ataxia, tremor, confusion, speech abnormalities, generalized tonic-clonic seizures. It binds the alpha-2 delta subunit of
mental slowing, and irritability. Zonisamide has been associated with Ca channels in the cerebral cortex, hippocampus, and spinal cord,
renal calculi in 1.5% of patients, and its carbonic anhydrase-inhibiting reducing the influx of Ca at nerve terminals, in turn reducing excitatory
effects may produce oligohidrosis in some children. Zonisamide should neurotransmitters release.
3,6,19,16,23,24
not be used in patients with known allergies to sulfonamides, as it may
produce allergic reactions in these individuals. Gabapentin, unlike many other newer AEDs, has a relatively poor
bioavailability of less than 60%, which is altered primarily by variable
Tigabine absorption via an L-amino acid transporter. At doses greater than 1,200mg,
Tigabine is used as add-on therapy in patients with partial or secondarily bioavailability further drops off to ~35%. Gabapentin neither binds to
generalized seizures. Tigabine, a derivative of the GABA uptake inhibitor plasma proteins nor is metabolized (and does not induce hepatic enzymes),
nipecotic acid, reversibly inhibits GABA transporter-1.
20,21
It binds 96% to and it is excreted entirely unchanged. Gabapentin has an elimination half-
plasma proteins and is metabolized by the hepatic P450 system. In a life of five to nine hours. In patients with compromised renal function,
patient co-medicated with enzyme-inducing drugs, tigabine’s plasma dosing must be adjusted according to creatinine clearance.
3,6,16,19
Owing to
half-life of four to eight hours may be reduced slightly to four to five its lack of drug interactions, lack of plasma protein-binding, and renal
hours. Its metabolism and removal from the body is reduced in liver excretion, gabapentin is particularly useful in patients with hepatic or renal
patients. Tigabine induces a minor decrease in valproate levels (valproate disease, or in patients on complex drug regimens.
3,10,23–25
It is typically well
has no effect on tigabine levels), but does not alter the efficacy of oral tolerated, with common adverse effects being somnolence, ataxia, and
contraceptives. P450-inducing drugs increase the clearance of tigabine dizziness. No significant serious idiosyncratic or systemic adverse effects of
by roughly two-thirds.
10,20–22
gabapentin have been reported.
23,25
US NEUROLOGY 51
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