Rx: (Jama 2004;291:615; Nejm 1996;334:168; Med Let 1995;37:37; Ann IM 1994;120:411)
Withdrawal successful in 2/3 if sx-free after 2 yr (Nejm 1988;318:942) unless focal neurol si's, focal-type seizure, or abnormal EEG; prophylactic rx beyond 1 week after head surgery/trauma no use (Nejm 1990;323:497); consider surgical rx if 1st-line drugs not enough (Jama 2008;300:2497; Nejm 1996;334:647)
Ketogenic (high-fat) diet improves seizure control in children (Peds 2001;108:898) but at atherogenic cost (Jama 2003;290:912)
Meds (Table 10.1)
1st:
- Phenytoin (Dilantin) 300-400 mg qd or fosphenytoin (Cerebyx) 10 mg/kg iv load then 5 mg/kg qd; therapeutic level = 10-20 µgm/cc,
2 h after last dose and 6 d after last dose change (Jama 1995;274:1622); correction for low albumin = measured level/0.2 × albumin + 0.1; for psychomotor (PC), not petit mal; adverse effects: displaces T3 and T4 from TBG, hence lowers levels, but TSH ok (Jama 1996;275:1495); rare idiosyncratic mono syndrome with hepatotoxicity (Nejm 1981;305:722); many drug interactions causing elevated levels, eg, with warfarin, disulfiram (Antabuse), INH, chloramphenicol, chlordiazepoxide (Librium), Thorazine, phenylbutazone, methylphenidate (Ritalin), estrogens; interactions lowering levels occur with phenobarbital, primidone, carbamazepine; phenytoin also decreases folate (hence fetal toxicity) and vit D levels; drug intoxication leads to a drunken state, cerebellar si's, gingival hyperplasia, rashes, hirsutism; $22/mo - Carbamazepine (Epilepsy; Partial Complex and Absence (Petit Mal) Types), or
- Valproic acid (Epilepsy; Partial Complex and Absence (Petit Mal) Types) (Lancet 2007;369:1016)
Although our colleagues call us old-fashioned for not using the more expensive options with perhaps fewer side effects and less need for drug monitoring choices, such as:
- Lamotrigine (Lamictal) (Epilepsy; Partial Complex and Absence (Petit Mal) Types), or
- Levetiracetam (Keppra), or
- Topiramate (Topamax)
2nd:
- Phenobarbital (Epilepsy; Partial Complex and Absence (Petit Mal) Types), or
- Primidone (Mysoline) (Epilepsy; Partial Complex and Absence (Petit Mal) Types), or
- Felbamate (Felbatol) (Epilepsy; Partial Complex and Absence (Petit Mal) Types)
of status epilepticus (Seizure)
Table 10.1Comparison of Traditional and Newer Antiepileptic Drugs
| Antiepileptic Drug | Protein Binding, % | Metabolism | Advantages | Disadvantages |
|---|---|---|---|---|
| Traditional agents | ||||
| Carbamazepine | 80 | Hepatic | Extensive patient exposure | Drug interactions, hyponatremia |
| Phenobarbital | 50 | Hepatic | Inexpensive, once-daily dosing | Sedation, cognitive effects |
| Phenytoin | 90 | Hepatic | Inexpensive, once-daily dosing | Nonlinear kinetics, drug interactions |
| Valproate | 95 | Hepatic | Broad spectrum | Weight gain, tremor, hair loss |
| Newer agents | ||||
| Felbamate | 25 | Hepatic | Broad spectrum | Risk of aplastic anemia, hepatotoxicity |
| Gabapentin | <10 | Renal | No drug interactions, rapid titration | Sedation, weight gain |
| Lamotrigine | 55 | Hepatic | Broad spectrum, favorable adverse effect profile | Slow titration, rash |
| Topiramate | 15 | Hepatic/renal | Broad spectrum | Slow titration, cognitive effects, kidney stones |
| Tiagabine | 95 | Hepatic | Novel mechanism of action | Multiple doses per day, tremor |
| Levetiracetam | <10 | Renal | No drug interactions, rapid titration | Rare behavioral changes |
| Oxcarbazepine | 50 | Hepatic | Less neurotoxic adverse effects than carbamazepine | Hyponatremia risk |
| Zonisamide | 40 | Hepatic | Broad spectrum, once-daily dosing | Slow titration, anorexia |
Reproduced with permission from LaRoche SM, Helmers SL. The new antiepileptic drugs: clinical applications. J Am Med Assoc. 2004:291:617. Copyright 2004, American Medical Association, all rights reserved.
Table 10.2Dosing and Cost Comparison
| Antiepileptic Drug | Starting Daily Dose, mg* | Daily Dosing Interval | Average Daily Maintenance Dose, mg | Titration Schedule† | Monthly Cost, S‡ |
|---|---|---|---|---|---|
| Traditional agents | |||||
| Carbamazepine | 400 | 3 Times | 1200 | Slow | 91.80 |
| Phenobarbital | 60 | Once | 150 | Slow | 2.70 |
| Phenytoin | 300 | Once | 300 | Rapid | 21.60 |
| Valproate | 750-1000 | 3 Times | 2000 | Rapid | 217.20 |
| Newer agents | |||||
| Gabapentin | 900 | 3 Times | 2400 | Rapid | 235.80 |
| Lamotrigine | 50 | Twice | 400 | Slow | 176.71 |
| Added to valproate | 25 (Every other day) | Twice | 100-200 | Slow | |
| Topiramate | 25-50 | Twice | 400 | Slow | 228.28 |
| Tiagabine | 4 | 2-4 Times | 48 | Slow | 206.40 |
| Levetiracetam | 1000 | Twice | 1500 | Rapid | 164.58 |
| Oxcarbazepine | 600 | Twice | 1200 | Slow | 193.20 |
| Zonisamide | 100 | Once | 200 | Slow | 113.40 |
*As recommended by each manufacturer's package insert.
†Rapid titration indicates maintenance dose achieved in less than 2 weeks; slow titration, an average of 2 to 12 weeks required to achieve maintenance dose.
‡Brand name prices from the 2002 Drug Topics Red Book. Retail prices may be higher or lower depending on the pharmacy and patient's insurance coverage.
Reproduced with permission from LaRoche SM, Helmers SL. The new antiepileptic drugs: clinical applications. J Am Med Assoc. 2004:291:616. Copyright 2004, American Medical Association, all rights reserved.