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.
PRECAUTIONS
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.
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