indication

For the treatment of refractory partial epilepsy.

pharmacology

Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures.

mechanism of action

The mechanism of action of mephenytoin is not definitely known, but extensive research strongly suggests that its main mechanism is to block frequency-, use- and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.

half life

Approximately 7 hours

drug interactions

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

Aminophylline: Decreased effect of both products

Amiodarone: Increases the effect of hydantoin

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

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

Capecitabine: Capecitabine increases the effect of hydantoin

Chloramphenicol: Increases phenytoin, modifies chloramphenicol

Chlordiazepoxide: Mephenytoin 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, mephenytoin, decreases the effect of the hormone agent, clomifene.

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

Clozapine: Hydantoin decreases the effect of clozapine

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

Cyclosporine: The hydantoin decreases the effect of cyclosporine

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

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

Diethylstilbestrol: The enzyme inducer, mephenytoin, 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, mephenytoin, decreases the effect of doxycycline.

Estradiol: The enzyme inducer, mephenytoin, 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, mephenytoin, may decrease the effect of the corticosteroid, fludrocortisone.

Fluorouracil: Fluorouracil increases the effect of hydantoin

Fluoxetine: Fluoxetine increases the effect of phenytoin

Flurazepam: Mephenytoin 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, mephenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.

Hydrocortisone: The enzyme inducer, mephenytoin, 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, mephenytoin, decreases the effect of the hormone agent, medroxyprogesterone.

Megestrol: The enzyme inducer, mephenytoin, 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: Mephenytoin 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 mephenytoin.

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

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

Prednisone: The enzyme inducer, mephenytoin, 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, mephenytoin, may decrease the effect of the corticosteroid, triamcinolone.

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