FDA label 22dc4c9c-50de-4f5b-a4f9-d1a042295ad2

WARNINGS Mesantoin ® (mephenytoin) should be used only after safer anticonvulsants have been given an adequate trial and have failed. As with all anticonvulsants, dose reduction must be gradual so as to minimize the risk of precipitating seizures. Patients should be cautioned about possible additive effects of alcohol and other central nervous system depressants. Acute alcohol intoxication may increase the anticonvulsant effect due to decreased metabolic breakdown. Chronic alcohol abuse may result in decreased anticonvulsant effect due to enzyme induction. 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.

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. 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.