MEPHENYTOIN

Chemistry - A hydantoin anticonvulsant, mephenytoin occurs a white, crystalline powder. It is veryslightly soluble in water. Mephenytoin is also known as methoin, methylphenylhydantoin orphenantoin.

Storage, Stability, Compatibility

Store mephenytoin tablets in well-closed containers at roomtemperature.

Pharmacology - MEPHENYTOIN

The anticonvulsant actions of mephenytoin and nirvanol are thought to mirrorthose of other hydantoin agents. By promoting sodium efflux from neurons it inhibits the spread ofseizure activity in the motor cortex. It is believed that excessive stimulation or environmentalchanges can alter the sodium gradient which may lower the threshold for seizure spread.
Hydantoins tend to stabilize this threshold and limit seizure propagation from epileptogenic foci.
Mephenytoin reportedly has some antiarrhythmic activity similar to that of phenytoin.

Pharmacokinetics - MEPHENYTOIN

Mephenytoin is absorbed from the GI tract. In humans, the onset of action isabout 30 minutes and duration of effect from 24-48 hours. Distribution characteristics have notbeen described. It is metabolized in the liver to an active metabolite, nirvanol, that has a very prolonged half life, giving the drug its long duration of action in humans and reasonable duration of effect in canines. It is also metabolized to a toxic compound, 5, 5-ethylphenylhydantoin, that may explain its increase hematopoietic toxicity.

Uses, Indications

Mephenytoin is a second or third line anticonvulsant in dogs, who have notresponded to phenobarbital and bromides. Its efficacy results from the long half life of its activemetabolite, nirvanol.

Contraindications, Precautions, Reproductive Safety

Mephenytoin is contraindicated in patients known to be hypersensitive to it or other hydantoins. Risk/benefit should be weighed if patient has preexisting blood dyscrasias or hepatic disease. Safe use of this drug has not been established during pregnancy or lactation.

Adverse Effects, Warnings

Adverse effects noted in dogs, include dose related (blood level related) sedation and ataxia. Experience with this agent in dogs is very limited and the precedingadverse effects may not be complete. In humans, dermatitis, lymphadenopathy, blood dyscrasias, hepatotoxicity, and fever have been reported. Mephenytoin causes a greater incidence of blooddyscrasias, or sedation in humans than does phenytoin (DPH).

Overdosage, Acute Toxicity

Symptoms of overdosage may include sedation, anorexia, and ataxiaat lower levels, and coma, hypotension and respiratory depression at higher levels. Severeintoxications should be handled supportively.

Drug Interactions

Note: the following interactions are from the human literature and are for thecompound, phenytoin. Because of the significant differences in pharmacokinetics in dogs, theirapplicability to mephenytoin are in question. They are included here as a caution. This list includesonly agents used commonly in small animal medicine, many more agents have been implicated inthe human literature. The following agents may increase the effects of phenytoin: allopurinol, cimetidine, chloramphenicol, diazepam, ethanol, isoniazid, phenylbutazone, sulfonamides, trimethoprim, valproic acid, salicylates, and chlorpheniramine.
The following agents may decrease the pharmacologic activity of phenytoin: barbiturates, diazoxide, folic acid, theophylline, antacids, antineoplastics, calcium (dietary andgluconate), enteral feedings, nitrofurantoin, and pyridoxine.
Phenytoin may decrease the pharmacologic activity of the following agents: corticosteroids, disopyramide, doxycycline, estrogens, quinidine, dopamine, and furosemide.
Phenytoin may decrease the analgesic properties of meperidine, but enhance its toxic effects. Thetoxicity of lithium may be enhanced. The pharmacologic effects of primidone may be altered.
Some data suggest that additive hepatotoxicity may result if phenytoin is used with eitherprimidone or phenobarbital. Weigh the potential risks versus the benefits before addingphenytoin to either of these drugs in dogs. Pyridoxine (Vitamin B6) may reduce the serum levelsof phenytoin.