indication

For the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.

pharmacology

Ethotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges.

mechanism of action

The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.

toxicity

Symptoms of overdose include drowsiness, loss of or impaired muscle coordination, nausea, visual disturbance, and, at very high doses, coma.

biotransformation

Hepatic. The drug exhibits saturable metabolism with respect to the formation of N-deethyl and p-hydroxyl-ethotoin, the major metabolites.

absorption

Fairly rapidly absorbed, however, the extent of oral absorption is not known.

half life

3 to 9 hours

drug interactions

Alprazolam: Ethotoin may increase the metabolism of alprazolam via CYP3A4.

Aminophylline: Decreased effect of both products

Amiodarone: Increases the effect of hydantoin

Aprepitant: The CYP3A4 inducer, ethotoin, may decrease the effect of aprepitant.

Betamethasone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, betamethasone.

Capecitabine: Capecitabine increases the effect of hydantoin

Chloramphenicol: Increases phenytoin, modifies chloramphenicol

Chlordiazepoxide: Ethotoin may increase the metabolism of chlordiazepoxide via CYP3A4.

Chlorpheniramine: The antihistamine increases the effect of hydantoin

Cimetidine: Increases the effect of hydantoin

Ciprofloxacin: Decreases the hydantoin effect

Clomifene: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, clomifene.

Clorazepate: Ethotoin may increase the metabolism of clorazepate via CYP3A4.

Clozapine: Hydantoin decreases the effect of clozapine

Conjugated Estrogens: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, conjugated estrogens.

Cyclosporine: The hydantoin decreases the effect of cyclosporine

Dexamethasone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, dexamethasone.

Diazepam: Ethotoin may increase the metabolism of diazepam via CYP3A4.

Diethylstilbestrol: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, diethylstilbestrol.

Disopyramide: The hydantoin decreases the effect of disopyramide

Disulfiram: Increases the effect of phenytoin

Doxycycline: The anticonvulsant, ethotoin, decreases the effect of doxycycline.

Estradiol: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, estradiol.

Ethinyl Estradiol: This product may cause a slight decrease of contraceptive effect

Felbamate: Increased phenytoin levels and decreased felbamate levels

Felodipine: The hydantoin decreases the effect of felodipine

Fluconazole: Increases the effect of hydantoin

Fludrocortisone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, fludrocortisone.

Fluorouracil: Fluorouracil increases the effect of hydantoin

Fluoxetine: Fluoxetine increases the effect of phenytoin

Flurazepam: Ethotoin may increase the metabolism of flurazepam via CYP3A4.

Fluvoxamine: Increases the effect of hydantoin

Folic Acid: Folic acid decreases the levels of hydantoin

Furosemide: The hydantoin decreases the effect of furosemide

Gabapentin: Increases the effect of hydantoin

Gefitinib: The CYP3A4 inducer, ethotoin, may decrease the serum concentration and therapeutic effects of gefitinib.

Hydrocortisone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, hydrocortisone.

Imatinib: The hydantoin decreases the levels of imatinib

Isoniazid: Isoniazid increases the effect of phenytoin in 20% of patients

Itraconazole: Phenytoin decreases the effect of itraconazole

Lamotrigine: Phenytoin may reduce levels of lamotrigine

Levonorgestrel: Phenytoin decreases the contraceptive effect

Mebendazole: The hydantoin decreases the efficiency of mebendazole

Medroxyprogesterone: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, medroxyprogesterone.

Megestrol: The enzyme inducer, ethotoin, decreases the effect of the hormone agent, megestrol.

Methadone: The hydantoin decreases the effect of methadone

Methotrexate: The antineoplasic agent decreases the effect of hydantoin

Methoxsalen: The hydantoin decreases the effect of psoralene

Mexiletine: The hydantoin decreases the effect of mexiletine

Midazolam: Ethotoin may increase the metabolism of midazolam via CYP3A4.

Mirtazapine: The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects

Norethindrone: This product may cause a slight decrease of contraceptive effect

Omeprazole: Omeprazole increases the effect of hydantoin

Oxcarbazepine: Oxcarbazepine increases the effect of hydantoin

Oxtriphylline: Decreased effect of both products

Oxyphenbutazone: The NSAID, oxyphenbutazone, may increase the hydantoin effect of ethotoin.

Phenylbutazone: The NSAID, phenylbutazone, may increase the hydantoin effect of ethotoin.

Prednisolone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisolone.

Prednisone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisone.

Quetiapine: Phenytoin decreases the effect of quetiapine

Rifampin: Rifampin decreases the effect of the hydantoin

Theophylline: Decreased effect of both products

Ticlopidine: Ticlopidine increases the effect of hydantoin

Triamcinolone: The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, triamcinolone.

Triazolam: Ethotoin may increase the metabolism of triazolam via CYP3A4.

Triprolidine: The CNS depressants, Triprolidine and Ethotoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.