Precautions
The liver is the chief site of biotransformation of PHENYTOIN ; patients with impaired liver function, elderly patients, or those who are gravely ill may show early signs of toxicity.
A small percentage of individuals who have been treated with phenytoin have been shown to metabolize the drug slowly. Slow metabolism may be due to limited enzyme availability and lack of induction; it appears to be genetically determined.
PHENYTOIN should be discontinued if a skin rash appears (see Warnings regarding drug discontinuation). If the rash is exfoliative, purpuric, or bullous or if lupus erythematosus, Stevens-Johnson syndrome or toxic epidermal necrolysis is suspected, use of this drug should not be resumed and alternative therapy should be considered (see Adverse Effects). If the rash is of a milder type (measles-like or scarlatiniform), therapy may be resumed after the rash has completely disappeared. If the rash recurs upon reinstitution of therapy, further phenytoin medication is contraindicated.
Hyperglycemia, resulting from the drug's inhibitory effects on insulin release, has been reported. Phenytoin may also raise the serum glucose level in diabetic patients.
Osteomalacia has been associated with PHENYTOIN therapy and is considered to be due to phenytoin's interference with vitamin D metabolism.
PHENYTOIN is not indicated for seizures due to hypoglycemic or other metabolic causes. Appropriate diagnostic procedures should be performed as indicated.
PHENYTOIN is not effective for absence (petit mal) seizures. If tonic-clonic (grand mal) and absence (petit mal) seizures are present, combined drug therapy is needed.
Serum levels of PHENYTOIN sustained above the optimal range may produce confusional states referred to as delirium, psychosis, or encephalopathy, or rarely, irreversible cerebellar dysfunction. Accordingly, at the first sign of acute toxicity, plasma level determinations are recommended. Dose reduction of PHENYTOIN therapy is indicated if plasma levels are excessive; if symptoms persist, termination is recommended (see Warnings).
Information for the Patient:
Patients taking phenytoin should be advised of the importance of adhering strictly to the prescribed dosage regimen, and of informing the physician of any clinical condition in which it is not possible to take the drug orally as prescribed, e.g. surgery, etc.
Patients should also be cautioned on the use of other drugs or alcoholic beverages without first seeking the physician's advice.
Patients should be instructed to call their physician if skin rash develops.
The importance of good dental hygiene should be stressed in order to minimize the development of gingival hyperplasia and its complications.
Do not use capsules which are discolored.
Laboratory Tests:
PHENYTOIN serum level determinations may be necessary to achieve optimal dosage adjustments.
Drug Interactions:
There are many drugs which may increase or decrease PHENYTOIN levels or which PHENYTOIN may affect. The most commonly occurring drug interactions are listed below.
Drugs which may increase PHENYTOIN serum levels include: chloramphenicol, dicumarol, disulfiram, tolbutamide, isoniazid, phenylbutazone, acute alcohol intake, salicylates, chlordiazepoxide, phenothiazines, diazepam, estrogens, ethosuximide, halothane, methylphenidate, sulfonamides, cimetidine, trazodone.
Drugs which may decrease PHENYTOIN levels include: carbamazepine, chronic alcohol abuse, reserpine. Moban brand of molindone HCl contains calcium ions which interfere with the absorption of phenytoin. Ingestion times of phenytoin and antacid preparations containing calcium should be staggered in patients with low serum phenytoin levels to prevent absorption problems.
Drugs which may either increase or decrease PHENYTOIN serum levels include: phenobarbital, valproic acid, and sodium valproate. Similarly, the effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.
Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and phenytoin dosage may need to be adjusted.
Drugs whose efficacy is impaired by phenytoin include: corticosteroids, coumarin anticoagulants, oral contraceptives, quinidine, vitamin D, digitoxin, rifampin, doxycycline, estrogens, furosemide.
Serum level determinations are especially helpful when possible drug interactions are suspected.
Drug/Laboratory Test Interactions:
PHENYTOIN may cause decreased serum levels of protein-bound iodine (PBI). It may also produce lower than normal values for dexamethasone or metyrapone tests. PHENYTOIN may cause increased serum levels of glucose, alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).
Lactation:
Infant breast-feeding is not recommended for women taking this drug because PHENYTOIN appears to be secreted in low concentrations in human milk.