Abrupt withdrawal of phenytoin in epileptic patients may precipitate status epilepticus. When in the judgment of the clinician the need for dosage reduction, discontinuation, or substitution of alternative anticonvulsant medication arises, this should be done gradually. In the event of an allergic or hypersensitivity reaction, more rapid substitution of alternative therapy may be necessary. In this case, alternative therapy should be an anticonvulsant not belonging to the hydantoin chemical class.
There have been a number of reports suggesting a relationship between phenytoin and the development of lymphadenopathy (local or generalized) including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s disease. Although a cause and effect relationship has not been established, the occurrence of lymphadenopathy indicates the need to differentiate such a condition from other types of lymph node pathology. Lymph node involvement may occur with or without symptoms and signs resembling serum sickness, eg, fever, rash, and liver involvement.
In all cases of lymphadenopathy, follow-up observation for an extended period is indicated and every effort should be made to achieve seizure control using alternative antiepileptic drugs.
Acute alcoholic intake may increase phenytoin serum levels, while chronic alcoholic use may decrease serum levels.
In view of isolated reports associating phenytoin with exacerbation of porphyria, caution should be exercised in using this medication in patients suffering from this disease.
Usage In Pregnancy
Clinical:
Risks to Mother. An increase in seizure frequency may occur during pregnancy because of altered phenytoin pharmacokinetics. Periodic measurement of plasma phenytoin concentrations may be valuable in the management of pregnant women as a guide to appropriate adjustment of dosage (see PRECAUTIONS, Laboratory Tests). However, postpartum restoration of the original dosage will probably be indicated.
Risks to the Fetus. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential harm to the fetus.
Prenatal exposure to phenytoin may increase the risks for congenital malformations and other adverse developmental outcomes. Increased frequencies of major malformations (such as orofacial clefts and cardiac defects), minor anomalies (dysmorphic facial features, nail and digit hypoplasia), growth abnormalities (including microcephaly), and mental deficiency have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy. There have also been several reported cases of malignancies, including neuroblastoma, in children whose mothers received phenytoin during pregnancy. The overall incidence of malformations for children of epileptic women treated with antiepileptic drugs (phenytoin and/or others) during pregnancy is about 10%, or two- to three-fold that in the general population. However, the relative contributions of antiepileptic drugs and other factors associated with epilepsy to this increased risk are uncertain and in most cases it has not been possible to attribute specific developmental abnormalities to particular antiepileptic drugs. Patients should consult with their physicians to weigh the risks and benefits of phenytoin during pregnancy.
Postpartum Period. A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth.
Preclinical:
Increased resorption and malformation rates have been reported following administration of phenytoin doses of 75 mg/kg or higher (approximately 120% of the maximum human loading dose or higher on a mg/m2 basis) to pregnant rabbits.
There is currently no manufacturer warning information available for this drug.
Phenytoin oral suspension is indicated for the control of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures.
Phenytoin serum level determinations may be necessary for optimal dosage adjustments (see DOSAGE AND ADMINISTRATIONand CLINICAL PHARMACOLOGYsections).
Phenytoin is related to the barbiturates in chemical structure, but has a five-membered ring. The chemical name is 5,5-diphenyl-2,4 imidazolidinedione, having the following structural formula:
Each Teaspoonful (5 mL) of Suspension for Oral Administration Contains: 125 mg of phenytoin USP with a maximum alcohol content not greater than 0.6 percent.
Inactive Ingredients: carboxymethylcellulose sodium, citric acid, FD&C Yellow No. 6, flavors, glycerin, magnesium aluminum silicate, polysorbate 40, purified water, sodium benzoate, sucrose, vanillin. May also contain sodium citrate to adjust pH.
