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| |
| Anticonvulsants after 1999 |
| Oxcarbazepine (Trileptal)
(OXC) |
 | Approved by FDA in 2000. |
| Pregnancy Category C |
| Use: partial seizure, may be used for monotherapy |
| Pharmocology:
 | Not metabolized to CBZ-epoxide. |
| Extensively metabolized to its pharmacologically
active 10-monohydroxy metabolite (MHD) with half life of about 9.3
+ or - 1.8 hours. |
| MHD is predominatly excreted by kidneys |
|
| Advantages:
| Markedly less hepatic enzyme induction. |
| No neutropenia. |
| Protein binding 40% |
| Linear kinetics |
|
| Side effects:
| Dose-related: fatigue, headache, dizziness,
ataxia. Incidence of side effects with OXC seems to be less than CBZ |
| Hyponatremia may occur especially with diuretic. |
| Idiosyncratic: rashes 6% vs 10% CBZ.
|
| If switching from Tegretol to Trileptal, other
drug level may rise, due to deinduction of liver enzymes. |
|
| Formulation: 150 mg, 300 mg, 600 mg scored, can break
in half. 300 mg/5 mL oral suspension |
| Dose:
| Dose-equivalency of OXC vs CBZ is 1.5:1 |
| Initiate at 300-600 mg/d (given bid), 900-2400 mg/d. |
| Serum level of MHD is available if desired,
50-200 mmol/ml. |
|
| Trileptal website |
|
| Levetiracetam (Keppra) |
| Approved by FDA in Nov 1999 |
| Pregnancy Category C |
| Use: Partial-onset seizures, adjunctive therapy |
| Pharmacology:
| rapidly absorbed |
| Pharmacokinetics: linear and steady
state in 2 days with bid dosing. |
| Protein binding: <10 percent |
| 66 percent renally excreted unchanged. |
| Plasma half-life 6 to 8 hours but is
increased in the elderly and in patients with renal
impairment. |
| No significant drug interactions. |
| does not induce hepatic enzymes, and its metabolism is not changed by other drugs |
|
| Adverse Effects:
| Dizziness, somnolence, fatigue |
| Mild decreases in hematocrit and white blood
cell count are seen rarely but do not require stopping the drug. |
|
| Idiosyncratic or serious side effect: none
recognised |
| Formulation: 250 mg (blue), 500 mg (yellow) and 750
mg (orange) tablets |
| Clinical Use: May be started at a
therapeutic dose of 500 mg BID, increase to
1000-3000 mg/day, give BID |
| Other use: May help spasticity in MS (Hawker. Arch
of Neurology. Dec 2003.) |
| Keppra
website |
|
| VIGABATRIN |
| Available in 50 countries. Not approved in U.S.
|
| Use: Partial-onset seizures, adjunctive therapy. Infantile spasms |
| Advantages: Effective, no drug interactions, renal excretion, long
duration of action. |
| Adverse Effects:
| Dose-related or early: somnolence, fatigue, headache, dizziness, mood
changes-agitation 7%, depression 5% |
| Idiosyncratic: psychosis 1.1%, Visual field constriction in 28% |
|
| Dosage: 500 mg/d, increase by 500 mg/d/week to 2-4 g/d |
|
| Zonisamide (Zonegran) (ZNS) |
| Approved in US in March 2000. |
| Use: Partial-onset seizures, adjunctive therapy |
| classified as a sulfonamide and unrelated to other
antiseizure agents, a weak carbonic anhydrase inhibitor. |
| Pregnancy Category C |
| Adverse Effects:
| Dose-related or early: somnolence, ataxia, cognitive effects |
| Idiosyncratic: rash (2.2%), kidney stones (.01% Japan, 2.6% elsewhere) |
|
| Preparation: 100 mg two-piece hard gelatin
capsule |
| Dose: 100 mg/d, increase 100 mg/d every 1 to 2 weeks to 200-800 mg/d |
| Pharmacology:
| Long half life, 50-68 hrs |
| hepatic metabolism,
renal excretion |
| causes no appreciable hepatic induction |
|
| Full
prescribing information |
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