The patient taking Mesantoin® (mephenytoin) must be kept under close medical supervision at all times since serious adverse reactions may emerge.

Because the primary site of degradation is the liver, it is recommended that screening tests of liver function precede introduction of the drug.

Some patients may show side reactions as the result of individual sensitivity. These reactions can be broken down into three types respectively according to severity: 1) blood dyscrasias; 2) skin and mucous membrane manifestations; and 3) central effects. The blood, skin and mucous membrane manifestations are the more important since they can be more serious in nature. Since mephenytoin has been reported to produce blood dyscrasia in certain instances, the patient must be instructed that in the event any unusual symptoms develop (e.g., sore throat, fever, mucous membrane bleeding, glandular swelling, cutaneous reaction), he/she must discontinue the drug and report for examination immediately. It is recommended that blood examinations be made (total white cell count and differential count) during the initial phase of administration. Such tests are best made: a) before starting medication; b) after 2 weeks on a low dosage; c) again after 2 weeks when full dosage is reached; d) thereafter, monthly for a year; e) from then on, every 3 months. If the neutrophils drop to between 2500 and 1600/cu.mm., counts are made every 2 weeks. Stop medication if the count drops to 1600/cu.mm.

General

Mesantoin® (mephenytoin) should not be discontinued abrubtly in patients in whom the drug is used to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and a threat to life.

Information for Patients

Mesantoin® (mephenytoin) may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly. Due to a possible additive sedative effect, Mesantoin® (mephenytoin) should be used with caution in combination with alcohol and other CNS depressant agents.

Drug Interactions

There have been no reports of drug interactions associated with the use of Mesantoin® (mephenytoin), however, caution should be used when Mesantoin® (mephenytoin) is coadministered with products known to interact with phenytoin.

Drug/Laboratory Test Interactions

Mephenytoin may cause decreased serum levels of protein-bound iodine. It may also produce lower than normal values for dexamethasone or metyrapone tests. Mephenytoin may cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase.

Carcinogenesis

Carcinogenesis has not been evaluated in animals

Pregnancy

Pregnancy Category D. See WARNINGS.

Nursing Mothers

Caution should be used when mephenytoin is administered to a nursing woman, since mephenytoin may appear in small quantities in the milk.

Newborn Infant

Since mephenytoin may cross the placenta and appear in the blood of the newborn infant, the possibility of withdrawal symptoms should be considered.

Pediatric Use

See DOSAGE AND ADMINISTRATION.

Adverse Reactions

A number of side effects and toxic reactions have been reported with Mesantoin® (mephenytoin) as well as with other hydantoin compounds. Many of these appear to be dose related while others seem to be a manifestation of a hypersensitivity reaction to these drugs.

Blood Dyscrasias

Leukopenia, neutropenia, agranulocytosis, thrombocytopenia and pancytopenia have occurred. Eosinophilia, monocytosis, and leukocytosis have been described. Simple anemia, hemolytic anemia, megaloblastic anemia and aplastic anemia have occurred but are uncommon. There has been an isolated report of lymphoma in the literature in a patient treated with mephenytoin for 17 years; a drug relationship has not been defined.