levine.qxp 1/8/08 10:20 am Page 50
Epilepsy
Table 1: The Administration of Antiepileptic Medications
Medication Metabolism Drug Interactions Adult Dosing Pediatric Dosing
Felbamate Hepatic. Valproate increased levels Start 1,200mg divided TID-QID, increase by Start 15mg/kg/day, titrate weekly
600 weekly to max of 3,600/day up to 45mg/kg/day
Increased PHT and CBZ *Reduce other AEDs by ≥20% *Reduce other AEDs by ≥20% when
P450 inducers reduce when starting felbamate starting felbamate
t
1/2
from 30 to14 hours *Approved for >14 years of age
Topiramate ~15% metabolized by P450-inducers may significantly Start 25mg daily or BID, titrate over Start 0.5–1mg/kg/day, titrate by
hepatic P450 system, reduce levels several weeks to months to typical effective 0.5–1mg/kg/day every 2 weeks to
~85% excreted unchanged May inactivate low-dose dose of 200–600mg/day divided BID typical effective dose of 9–11mg/kg/day
in urine. oral contraceptives *In renal failure, dosages must be reduced *In renal failure, dosages must be reduced
*Approved for >2 years of age
Oxcarbamazepine Hepatic metabolism with May inactivate oral contraceptives Start 600mg/day divided BID, titrate to Start 10mg/kg/day divided BID, titrate to
renal excretion. 400mg/day 30mg/kg
*May be substituted for carbamazepine with *Approved for >4 years of age
3:2 oxcarbazepine:carbamazepine ratio
Lamotrigine Hepatic metabolism with P450-inducers may significantly Administered BID. Slow titration significantly Administered BID. Slow titration significantly
renal excretion. reduce t
1/2
improves tolerability. Dosing/titration depends improves tolerability. Dosing/titration
on AED co-administration, with a slower depends on AED co-administration, with a
Valproate increases lamotrigine titration with enzyme-inhibiting AEDs. slower titration with enzyme-inhibiting AEDs
levels by increasing t
1/2
Starter packs available with specific titrations If given with valproate, start at
depending on co-administered medications 0.15mg/kg/day divided BID, with escalations
every 1–2 weeks to a maximum of 5mg/kg.
If on enzyme inducers, start at 0.6mg/kg/day
divided BID, titrate to a maximum of 15mg/kg.
*Approved for ≥2 years of age
Zonisamide ~70% hepatic metabolism t
1/2
may decrease (from 63 to Start 100mg/day, titrate every two weeks,by Start 2mg/kg/day, divided BID, titrate by
without P450 induction. 27–46 hours) when co-administered 100mg/day to goal of 100–60mg/day (there 2mg/kg/day every two weeks to goal
with pheytoin, carbamazepine, is no suggestion of increasing response above of 8–10mg/kg/day
phenobarbital, or valproate 400mg/day). Since zonisamide is metabolized *Approved for ≥12 years of age
hepatically and excreted renally, patients with
renal or hepatic disease may require slower
titration and more frequent monitoring.
Due to zonisamide’s long t
1/2
, up to two
weeks may be required to achieve steady state
Tigabine Hepatic, P450; metabolism P450-inducers decrease t
1/2
Start 4mg/day, titrate 4–8mg daily each week Start 0.1mg/kg/day, divided TID, titrate by
and excretion are reduced in (from 4–8 to 4–5 hours) and increase to a goal of 32–56mg/day 0.1mg/kg/day weekly to goal of
liver patients. clearance by ~
2
⁄3 0.4mg/kg/day (max of 32mg/day)
*Approved for ≥12 years of age
Gabapentin Not metabolized and is excreted Antacids may decrease bioavailibility Start 300mg TID (900mg/day), titrate Start 5mg/kg/day, divided TID, titrate by
in unchanged form. In patients weekly to a maximum of 4,800mg daily 5mg/kg/day to goal of 15–20 mg/kg/day
with decreased renal function, (though often titration stopped at 3,600mg (max of 60mg/kg/day)
dosing should be adjusted daily, as bioavailability rapidly drops as *Approved for >3 years of age
according to Cr clearance. dosage escalates)
Gabapentin is removed by
hemodialysis.
Levetiracetam ~ 27% metabolized; cleared Start 500mg BID, titrate weekly by Start 5–10mg/kg/day, divided daily or BID,
by glomerular filtration with 500–1,000mg daily to maximum of 3,000mg titrate by 5–10mg/kg/day weekly to goal of
partial tubular reabsorption 30–50mg/kg/day (max of 100mg/kg/day)
~
2
⁄3 excreted unchanged in *Approved for ≥4 years of age
urine. In renal insufficiency,
elimination half-life prolonged;
removed during hemodialysis.
Pregabalin Not significantly metabolized; Start 15mg/day divided BID or TID, *Approved for adult usage only
excreted unchanged by kidneys. titrate to maximum dose of 600mg/day
In patients significant renal
dysfunction (creatine clearance
<60ml/minute), doses must be lowered.
TID-QID = three to fours times daily; PHT = pulmonary hypertension; CBZ = carbamazepine; AEDs = aintiepileptic drugs; BID = twice daily.
50 US NEUROLOGY
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