Usage in Pregnancy

The effects of Mesantoin® (mephenytoin) in human pregnancy and on nursing infants have not been systematically investigated.

Reports suggest an association between the use of anticonvulsant drugs by women with epilepsy and an elevated incidence of birth defects in children born to these women. Data are more extensive with respect to diphenylhydantoin and phenobarbital, but these are also the most commonly prescribed anticonvulsants; less systematic or anecdotal reports suggest a possible similar association with the use of all known anticonvulsant drugs.

The reports suggesting an elevated incidence of birth defects in children of drug-treated epileptic women cannot be regarded as adequate to prove a definite cause and effect relationship. There are intrinsic methodological problems in obtaining adequate data on drug teratogenicity in humans; the possibility also exists that other factors, e.g., genetic factors or the epileptic condition itself, may be more important than drug therapy in leading to birth defects. The great majority of mothers on anticonvulsant medication deliver normal infants. It is important to note that anticonvulsant drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazards to the developing embryo or fetus.

Hydantoins can cause fetal harm when administered to a pregnant woman. There have been two cases in which the following have been associated with the use of Mesantoin® (mephenytoin): neonatal patent ductus arteriosus, coarctation of the aorta, ventricular septal defect, atrial septal defect, downslanting palpebral fissures, hypoplastic maxilla, big nose, and facial hemangiomas. In both these cases concomitant drugs (i.e. alcohol and primidone) were used.

The prescribing physician will wish to weigh these considerations in treating or counseling epileptic women of child-bearing potential. If Mesantoin® (mephenytoin) is used during pregnancy, or if the patient becomes pregnant while taking Mesantoin® (mephenytoin), the patient should be apprised of the potential hazard to the fetus. 

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.

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.

Skin and Mucous Membrane Manifestations

Maculopapular, morbilliform, scarlatiniform, urticarial, purpuric (associated with thrombocytopenia) and non-specific skin rashes have been reported. Exfoliative dermatitis, erythema multiforme (Stevens-Johnson Syndrome), toxic epidermal necrolysis and fatal dermatitides have been described on rare occasions. Skin pigmentation and rashes associated with a lupus erythematosus syndrome have also been reported.

Central Effects

Drowsiness is dose-related and may be reduced by a reduction in dose. Ataxia, diplopia, nystagmus, dysarthria, fatigue, irritability, choreiform movements, depression, and tremor have been encountered.

Nervousness, nausea, vomiting, sleeplessness and dizziness may occur during the initial stages of therapy. Generally, these symptoms are transient, often disappearing with continued treatment.

Mental confusion and psychotic disturbances and increased seizures have been reported, but a definite causal relationship with the drug is uncertain.

Miscellaneous

Hepatitis, jaundice and nephrosis have been reported but a definite cause and effect relationship between the drug and these effects has not been established.

Alopecia, weight gain, edema, photophobia, conjunctivitis, and gum hyperplasia have been encountered.

Polyarthropathy, pulmonary fibrosis, lupus erythematosus syndrome, lymphoma and lymphadenopathy which simulates Hodgkin’s Disease have also been observed.

Abuse

To date, there have been no reports of abuse with the use of Mesantoin® (mephenytoin).

Dependence

To date, there have been no reports of dependence (psychological or physical) with the use of Mesantoin® (mephenytoin).

Lethal Dose

While the fatal dose of Mesantoin® (mephenytoin) has not been established, the minimum lethal dose for adults is probably in the region of 3 to 5 gm.

Symptoms and signs of overdosage include: ataxia, dysarthria, nystagmus, drowsiness, confusion and coma with areflexia.

Hypotension, which may proceed to a shock-like state, can also occur.

Tachycardia and arrhythmias of ventricular origin have also been reported.

Terminal hyperpyrexia was reported in one fatal case.

Transient thrombocytopenia, hemorrhagic bullae and petechal rash have been reported following a single overdose.

Treatment

There is no specific antidote for an overdosage of Mesantoin® (mephenytoin).

General measures include:

• Elimination of offending drug by induction of emesis, gastric lavage, catharsis, or activated charcoal.
• Maintenance of pulmonary ventilation with suction or endotracheal intubation.

Correction of hypotension, using a pressor agent.

• Maintenance of normal body temperature.

EKG Monitoring

The hydantoins as a group are known to have a depressive effect on the heart, particularly in high doses. If arrhythmias occur, regular EKG monitoring should begin at once.