Phenytoin (diphenylhydantoin, phenytoin sodium)
Brand Name: Dilantin-125, Dilantin Infatab, Dilantin Injection, Dilantin Kapseals, Diphenylan (CAN), Phenytek, Phenytex (CAN)
Pregnancy Category D
Drug classes: Antiepileptic agent, Hydantoin
Has antiepileptic activity without causing general CNS depression; stabilizes neuronal membranes and prevents hyperexcitability caused by excessive stimulation; limits the spread of seizure activity from an active focus; also effective in treating cardiac arrhythmias, especially those induced by digitalis; antiarrhythmic properties are very similar to those of lidocaine; both are class IB antiarrhythmics.
· Control of grand mal (tonic-clonic) and psychomotor seizures
· Prevention and treatment of seizures occurring during or following neurosurgery
· Control of status epilepticus of the grand mal type (parenteral administration)
· Unlabeled uses: antiarrhythmic, particularly in digitalis-induced arrhythmias (IV preparations); treatment of trigeminal neuralgia (tic douloureux)
· Contraindicated with hypersensitivity to hydantoins, sinus bradycardia, sinoatrial block, Stokes-Adams syndrome, pregnancy (data suggest an association between antiepileptic drug use and an elevated incidence of birth defects; however, do not discontinue antiepileptic therapy in pregnant women who are receiving such therapy to prevent major seizures; this is likely to precipitate status epilepticus, with attendant hypoxia and risk to both mother and fetus), lactation.
Nystagmus, ataxia, dysarthria, slurred speech, mental confusion, dizziness, drowsiness, insomnia, transient nervousness, motor twitchings, fatigue, irritability, depression, numbness, tremor, headache, photophobia, diplopia, conjunctivitis
Dermatologic reactions, scarlatiniform, morbilliform, maculopapular, urticarial and nonspecific rashes; serious and sometimes fatal dermatologic reactions--bullous, exfoliative, or purpuric dermatitis, lupus erythematosus, and Stevens-Johnson syndrome, toxic epidermal necrolysis, hirsutism, alopecia, coarsening of the facial features, enlargement of the lips, Peyronie's disease
Nausea, vomiting, diarrhea, constipation, gingival hyperplasia, toxic hepatitis, liver damage, sometimes fatal; hypersensitivity reactions with hepatic involvement, including hepatocellular degeneration and fatal hepatocellular necrosis
Hematopoietic complications, sometimes fatal: thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, pancytopenia; macrocytosis and megaloblastic anemia that usually respond to folic acid therapy; eosinophilia, monocytosis, leukocytosis, simple anemia, hemolytic anemia, aplastic anemia, hyperglycemia
· Increased pharmacologic effects with chloramphenicol, cimetidine, disulfiram, isoniazid, phenacemide, phenylbutazone, sulfonamides, trimethoprim
· Complex interactions and effects when phenytoin and valproic acid are given together; phenytoin toxicity with apparently normal serum phenytoin levels; decreased plasma levels of valproic acid; breakthrough seizures when the two drugs are given together
· Decreased pharmacologic effects with antineoplastics, diazoxide, folic acid, sucralfate, rifampin, theophylline (applies only to oral hydantoins, absorption of which is decreased)
· Increased pharmacologic effects and toxicity with primidone, oxyphenbutazone, amiodarone, chloramphenicol, fluconazole, isoniazid
· Increased hepatotoxicity with acetaminophen
· Decreased pharmacologic effects of the following: corticosteroids, cyclosporine, disopyramide, doxycycline, estrogens, furosemide, levodopa, methadone, metyrapone, mexiletine, hormonal contraceptives, quinidine, atracurium, gallamine triethiodide, pancuronium, tubocurarine, vecuronium, carbamazepine, diazoxide
· Severe hypotension and bradycardia when IV phenytoin is given with dopamine
· Use only clear parenteral solutions; a faint yellow color may develop, but this has no effect on potency. If the solution is refrigerated or frozen, a precipitate might form, but this will dissolve if the solution is allowed to stand at room temperature. Do not use solutions that have haziness or a precipitate.
· Administer IV slowly to prevent severe hypotension; the margin of safety between full therapeutic and toxic doses is small. Continually monitor patient's cardiac rhythm and check BP frequently and regularly during IV infusion. Suggest use of fosphenytoin sodium if IV route is needed.
· Monitor injection sites carefully; drug solutions are very alkaline and irritating.
· Monitor for therapeutic serum levels of 10–20 mcg/mL.
· Give oral drug with food to enhance absorption and to reduce GI upset.
· Recommend that the oral phenytoin prescription be filled with the same brand each time; differences in bioavailability have been documented.
· Suggest that adult patients who are controlled with 300-mg extended phenytoin capsules try once-a-day dosage to increase compliance and convenience.
· Reduce dosage, discontinue phenytoin, or substitute other antiepileptic medication gradually; abrupt discontinuation may precipitate status epilepticus.
· Phenytoin is ineffective in controlling absence (petit mal) seizures. Patients with combined seizures will need other medication for their absence seizures.
· Discontinue drug if rash, depression of blood count, enlarged lymph nodes, hypersensitivity reaction, signs of liver damage, or Peyronie's disease (induration of the corpora cavernosa of the penis) occurs. Institute another antiepileptic drug promptly.
· Monitor hepatic function periodically during long-term therapy; monitor blood counts, urinalysis monthly.
· Monitor blood or urine sugar of patients with diabetes mellitus regularly. Adjustment of dosage of hypoglycemic drug may be necessary because antiepileptic drug may inhibit insulin release and induce hyperglycemia.
· Have lymph node enlargement occurring during therapy evaluated carefully. Lymphadenopathy that simulates Hodgkin's disease has occurred. Lymph node hyperplasia may progress to lymphoma.
· Monitor blood proteins to detect early malfunction of the immune system (eg, multiple myeloma).
· Arrange dental instruction in proper oral hygiene technique for long-term patients to prevent development of gum hyperplasia.
Phenytoin (diphenylhydantoin, phenytoin sodium)
In making a Drug Study,