phenytoin (diphenylhydantoin, phenytoin sodium)

(fen' i toe in)

Dilantin-125, Dilantin Infatab, Dilantin Injection, Dilantin Kapseals,
Phenytek, Phenytex (CAN)

Pregnancy Category D

Drug classes
Antiepileptic
Hydantoin

Therapeutic actions
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.

Indications
• Control of grand mal (tonic-clonic) and psychomotor seizures
• Prevention and treatment of seizures occurring during or following neurosurgery
• Parenteral administration: Control of status epilepticus of the grand mal type
• Unlabeled uses: Antiarrhythmic, particularly in digitalis-induced arrhythmias (IV
preparations); treatment of trigeminal neuralgia (tic douloureux)

Contraindications and cautions

• Contraindicated with hypersensitivity to hydantoins, sinus bradycardia, sinoatrial
block, Stokes-Adams syndrome, pregnancy (data suggest an association between
antiepileptic 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.
• Use cautiously with acute intermittent porphyria, hypotension, severe myocardial
insufficiency, diabetes mellitus, hyperglycemia.

Available forms
Chewable tablets—50 mg; oral suspension—125 mg/5 mL; capsules—30, 100 mg; ER
capsules—200, 300 mg; injection—50 mg/mL

Dosages
ADULTS
Phenytoin sodium, parenteral
• Status epilepticus: 10–15 mg/kg by slow IV. For maintenance, 100 mg PO or IV q
6–8 hr. Higher doses may be required. Do not exceed an infusion rate of
50 mg/min. Follow each IV injection with an injection of sterile saline through the
 same needle or IV catheter to avoid local venous irritation by the alkaline
solution. Continuous IV infusion is not recommended.
• Neurosurgery (prophylaxis): 100–200 mg IM q 4 hr during surgery and the
postoperative period (IM route is not recommended because of erratic absorption,
pain and muscle damage at the injection site).
• IM therapy in a patient previously stabilized on oral dosage: Increase dosage by
50% over oral dosage. When returning to oral dosage, decrease dose by 50% of
the original oral dose for 1 wk to prevent excessive plasma levels due to
continued absorption from IM tissue sites. Avoid IM route of administration if
possible due to erratic absorption and pain and muscle damage at injection site.
Phenytoin and phenytoin sodium, oral
Individualize dosage. Determine serum levels for optimal dosage adjustments. The
clinically effective serum level is usually between 10 and 20 mcg/mL.
• Loading dose (hospitalized patients without renal or liver disease): Initially, 1 g
of phenytoin capsules (phenytoin sodium, prompt) is divided into 3 doses
(400 mg, 300 mg, 300 mg) and given q 2 hr. Normal maintenance dosage is then
instituted 24 hr after the loading dose with frequent serum determinations.
• No previous treatment: Start with 100 mg tid PO. Satisfactory maintenance
dosage is usually 300–400 mg/day. An increase to 600 mg/day may be necessary.
• Single daily dosage (phenytoin sodium, extended): If seizure control is established
with divided doses of three 100-mg extended phenytoin sodium capsules per day,
once-a-day dosage with 300 mg PO may be considered.
PEDIATRIC PATIENTS
Phenytoin sodium, parenteral
• Status epilepticus: Administer phenytoin IV. Determine dosage according to
weight in proportion to dose for a 150-lb (70-kg) adult (see adult dosage above;
see Appendix Calculating Pediatric Doses). Pediatric dosage may be calculated
on the basis of 250 mg/m2. Dosage for infants and children also may be calculated
on the basis of 10–15 mg/kg, given in divided doses of 5–10 mg/kg. For neonates,
15–20 mg/kg in divided doses of 5–10 mg/kg is recommended.
Phenytoin and phenytoin sodium, oral
Children not previously treated: Initially, 5 mg/kg/day in 2–3 equally divided doses.
Subsequent dosage should be individualized to a maximum of 300 mg/day. Daily
maintenance dosage is 4–8 mg/kg. Children > 6 yr may require the minimum adult dose
of 300 mg/day.
GERIATRIC PATIENTS AND PATIENTS WITH HEPATIC IMPAIRMENT
Use caution and monitor for early signs of toxicity; phenytoin is metabolized in the liver.

Pharmacokinetics
Route Onset Peak Duration
Oral Slow 2–12 hr 6–12 hr
IV 1–2 hr Rapid 12–24 hr

Metabolism: Hepatic; T1/2: 6–24 hr

Distribution: Crosses placenta; enters breast milk
Excretion: Urine
IV facts
Preparation: Administration by IV infusion is not recommended because of low
solubility of drug and likelihood of precipitation; however, this may be feasible if proper
precautions are observed. Use suitable vehicle of 0.9% sodium chloride or lactated
Ringer's injection, appropriate concentration; prepare immediately before administration,
and use an in-line filter.
Infusion: Infuse slowly in small increments, each 25–50 mg over 1–5 min; infuse flush
immediately after drug to reduce the risk of damage to vein and tissues.
Incompatibilities: Do not combine with other medications in solution.
Y-site incompatibilities: Do not give with potassium chloride.

Adverse effects
Some adverse effects are related to plasma concentrations, as follows:
Plasma Adverse Effects
Concentration
5–10 mcg/mL Some therapeutic effects
10–20 mcg/mL Usual therapeutic range
> 20 mcg/mL Far-lateral nystagmus risk
> 30 mcg/mL Ataxia is usually seen
> 40 mcg/mL Significantly diminished
mental capacity
• CNS: Nystagmus, ataxia, dysarthria, slurred speech, mental confusion, dizziness,
drowsiness, insomnia, transient nervousness, motor twitchings, fatigue,
irritability, depression, numbness, tremor, headache, photophobia, diplopia,
conjunctivitis
• CV: CV collapse, hypotension (when administered rapidly IV; not to exceed
50 mg/min)
• Dermatologic: 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
• GI: Nausea, vomiting, diarrhea, constipation, gingival hyperplasia, toxic
hepatitis, liver damage, sometimes fatal; hypersensitivity reactions with hepatic
involvement, including hepatocellular degeneration and fatal hepatocellular
necrosis
• GU: Nephrosis
• Hematologic: 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
• IV use complications: Hypotension, transient hyperkinesia, drowsiness,
nystagmus, circumoral tingling, vertigo, nausea, cardiovascular collapse, CNS
depression
• Respiratory: Pulmonary fibrosis, acute pneumonitis
 • Other: Lymph node hyperplasia, sometimes progressing to frank malignant
lymphoma, monoclonal gammopathy and multiple myeloma (prolonged therapy),
polyarthropathy, osteomalacia, weight gain, chest pain, periarteritis nodosa

Interactions
Drug-drug
• 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

Drug-lab test
• Interference with the metyrapone and the 1-mg dexamethasone tests for at least 7
days

Nursing considerations
Assessment
• History: Hypersensitivity to hydantoins; sinus bradycardia, AV heart block,
Stokes-Adams syndrome, acute intermittent porphyria, hypotension, severe
myocardial insufficiency, diabetes mellitus, hyperglycemia, pregnancy, lactation
• Physical: T; skin color, lesions; lymph node palpation; orientation, affect,
reflexes, vision exam; P, BP; R, adventitious sounds; bowel sounds, normal
output, liver evaluation; periodontal exam; liver function tests, urinalysis, CBC
and differential, blood proteins, blood and urine glucose, EEG and ECG

Interventions
• 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.

Teaching points
• Take this drug exactly as prescribed, with food to enhance absorption and reduce
GI upset; be especially careful not to miss a dose if you are on once-a-day
therapy.
• Do not discontinue this drug abruptly or change dosage, except on the advice of
your prescriber.
• Maintain good oral hygiene (regular brushing and flossing) to prevent gum
disease; arrange frequent dental checkups to prevent serious gum disease.
• Arrange for frequent checkups to monitor your response to this drug.
• Monitor your blood or urine sugar regularly, and report any abnormality to your
health care provider if you have diabetes.
 • This drug is not recommended for use during pregnancy. It is advisable to use
some form of contraception other than hormonal contraceptives.
• Wear a medical alert tag so that any emergency medical personnel will know that
you have epilepsy and are taking antiepileptic medication.
• These side effects may occur: Drowsiness, dizziness, confusion, blurred vision
(avoid driving or performing other tasks requiring alertness or visual acuity); GI
upset (take drug with food, eat frequent small meals).
• Report rash, severe nausea or vomiting, drowsiness, slurred speech, impaired
coordination (ataxia), swollen glands, bleeding, swollen or tender gums,
yellowish discoloration of the skin or eyes, joint pain, unexplained fever, sore
throat, unusual bleeding or bruising, persistent headache, malaise, any indication
of an infection or bleeding tendency, abnormal erection, pregnancy.

Adverse effects in Italic are most common; those in Bold are life-threatening.