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| Overview of anticonvulsants 1993
- 1998 |
| Felbamate (Felbatol) (FBM) |
 | FDA approved use:
 | Partial-onset seizures, adults and children, adjunctive and monotherapy |
| Lennox-Gastaut Syndrome |
|
| Clinical Use:
| Refractory patients unresponsive to other drugs who
are not surgical candidates |
| Patients who had unacceptable sedation from other drugs |
| Lennox-Gastaut, especially frequent atonic seizures. |
|
| Formulations:
| Susp: 600mg/5ml. Tab: 400, 600mg |
| Dose: Start with 600-1200 mg/d, increase by 600 mg q 1-2 wks to 3600
mg/d. |
|
| Pharmacology
| Therapeutic level: 40-100 ug/ml |
| T 1/2: 20 hr, better tolerated if given tid |
| Protein binding: 25% |
| Metabolism: 50/50 hepatic/renal |
|
| Advantage: Nonsedating, broad spectrum |
| Disadvantages & Adverse Effects:
| Dose-related: GI effects, anorexia, insomnia, headaches |
| Idiosyncratic: aplastic anemia or liver failure 1/5000 patients. Avoid in
patients with previous history of blood dyscrasias, autoimmune diseases, liver problem,
hematological side effects from other drugs. |
|
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| Gabapentin (Neurontin) (GBP) |
| FDA-approved in 1994 for partial-onset seizures in adults, adjunctive |
| Clinical Use:
| Benign Sylvian-Rolandic epilepsy ( drug of choice if
treatment is needed at all) |
| Patients with liver disease |
| Patients in whom lack of drug interaction is critical, such as in
transplant patients. |
| Also widely used to treat neuropathic pain,
migraine, mood disorders, and social phobia. |
|
| Formulations:
| Cap: 100, 300, 400 mg |
| Tablet: 600 mg, 800 mg |
|
| Dose: 600- 4800mg /day, given q8 to q6h |
| Pharmacology:
| T 1/2: 5 hr |
| Prot binding: 0% |
| Metabolism: Renally excreted, not metabolized |
| Mechanism: Increases brain GABA |
|
| Advantages:
| Lack of serious side effects |
| No drug interactions |
| Some patients report feeling of well-being, reduced pain and headache |
|
| Disadvantages & side effects:
| Dose-related: somnolence, dizziness, ataxia, fatigue, weight gain |
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|
| Lamotrigine (Lamictal) (LTG) |
| FDA-approved use: partial-onset seizures, adults (over 16),
adjunctive, and monotherapy after withdrawal of other drugs |
| Clinical Use:
| Monotherapy for refractory partial seizures or when other drugs produce
sedative effects |
| Juvenile myoclonic epilepsy refractory to valproate |
| Lennox-Gastaut refractory to valproate |
|
| Formulations:
| Tab: 5 mg Chewable; 25, 100, 150, 200 mg |
|
| Dose:
| Start slow with 0.2 to 0.5 mg/kg/day, given qd to tid. Up to 200-700 mg
/day |
| Slow dose escalation is mandatory to avoid rash |
| Examine patient immediately if developed
rash |
|
| Pharmacology:
| T1/2 varies with drug interactions: 29 hrs monotherapy, 15 hrs with
enzyme inducers, 60-70 hrs with valproate. |
| Metabolism: hepatic |
| Protein binding: 50% |
| Therapeutic range not established: monotherapy levels of 10-20 often well
tolerated, less as polytherapy. |
|
| Advantages:
| Improved alertness |
|
| Disadvantages & side effects:
| Dose-related: dizziness, diplopia, ataxia, headache |
| Idiosyncratic: potentially life-threatening rashes in 1/1000; rare
Stevens-Johnson, anticonvulsant hypersensitivity syndrome. FDA Warning alert 1997 |
| Patients with a history of allergy to other drugs should not be treated with lamotrigine |
|
|
| Topiramate (Topamax) (TPM) |
| FDA-approved use: partial-onset seizures, primary
generalized tonic-clonic seizures, adjunctive therapy. |
| FDA Approved 1996 Dec |
| Clinical Use:
| Refractory partial-onset epilepsy syndromes |
| Other syndromes including partial or GTC, at lower doses (100-300 mg/day) |
| Juvenile myoclonic epilepsy refractory to valproate, or when weight gain
is a major problem. |
|
| Pregnancy Category C |
| Formulations:
| Tab 25, 100, 200 mg |
|
| Dose: Initial 25-50 mg/day, slow increase by 50 mg/week. |
| Pharmocology:
| T 1/2: 21 hr |
| Protein binding: 20% |
| Metabolism: 75% renal, 25% hepatic |
|
| Advantages:
| Effective, lack of serious side effects, few drug interactions |
|
| Disadvantages & side effects:
| Moderately high incidence of cognitive and affective side effects |
| Dose-related or early: cognitive problems, somnolence, weight loss, mood
changes, paresthesia |
| Idiosyncratic: psychosis 1%, kidney stones 1.5% |
|
|
| Tiagabine (Gabitril)
(TGB) |
| FDA approved in Nov 1997 for use as adjunctive therapy in patients 12
years and older with partial seizures |
| Formulations: Tab: 4, 12, 16, 20 mg |
| Dose: start with 4 mg qd, increase weekly by 4-8 mg/d, effective
dose 32 to 64 mg/day given bid or tid. |
| Pharmocology:
| T 1/2: 7 - 9 hr, may be 4 to 7 hours in patients receiving drugs that
induce hepatic enzymes |
| Prot binding: highly (96%) protein bound |
| Metabolism: hepatic |
| Mechanism: blocks glial GABA uptake |
|
| Disadvantages & side effects:
| Dose-related: dizziness, fatigue, tremor, somnolence, mood changes |
| Idiosyncratic: none known |
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| Diazepam rectal gel (Diastat) (DZP) |
| Use: Intermittent use for increased seizure activity |
| Formulation: 2.5, 5, 10, 15, 20 mg rectal gel delivery system |
| Dose: 0.2 mg/kg |
| Usual Adult dose: 10 to 20 mg |
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| Further Reading & References |
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