phenytoin
Dilantin-125, Dilantin Infatab

phenytoin sodium (prompt)
Dilantin

phenytoin sodium (extended)
Dilantin Kapseals, Phenytek

Available forms
Available by prescription only
phenytoin
Oral suspension: 30 mg/5 ml ◆, 125 mg/5 ml
Tablets (chewable): 50 mg
phenytoin sodium (extended)
Capsules: 30 mg (27.6-mg base), 100 mg (92-mg base), 200 mg (184-mg base), 300 mg (276-mg base)
phenytoin sodium (prompt)
Capsules: 100 mg
Injection: 50 mg/ml (46-mg base)

Indications and dosages
 Generalized tonic-clonic seizures, status epilepticus, nonepileptic seizures (post-head trauma, Reye’s syndrome). Adults: Loading dose is 10 to 15 mg/kg I.V. slowly, not to exceed 50 mg/minute; oral loading dose is 1 g divided into three doses (400 mg, 300 mg, 300 mg) given at 2-hour intervals. Once controlled, maintenance dose is 300 mg P.O. daily (extended only); initially use a dose divided t.i.d. (extended or prompt).
Children: Loading dose is 15 to 20 mg/kg I.V. at 50 mg/minute, or P.O. divided q 8 to 12 hours; then start maintenance dose of 4 to 8 mg/kg P.O. or I.V. daily, divided q 12 hours.
 Neuritic pain (migraine, trigeminal neuralgia, and Bell’s palsy). Adults: 200 to 600 mg P.O. daily in divided doses.
 Skeletal muscle relaxant. Adults: 200 to 600 mg P.O. daily, p.r.n.
 Ventricular arrhythmias unresponsive to lidocaine or procainamide, and arrhythmias induced by cardiac glycosides ◇. Adults: 50 to 100 mg q 10 to 15 minutes, p.r.n., not to exceed 15 mg/kg. Infusion rate shouldn’t exceed 50 mg/minute (slow I.V. push).
Alternative method: 100 mg I.V. q 15 minutes until adverse effects develop, arrhythmias are controlled, or 1 g has been given. Also may administer entire loading dose of 1 g I.V. slowly at 25 mg/minute. Can be diluted in normal saline solution. I.M. route isn’t recommended because of pain and erratic absorption.
 Prophylactic control of seizures during neurosurgery. Adults: 100 to 200 mg I.V. at intervals of about 4 hours during perioperative and postoperative periods.

Pharmacodynamics
Anticonvulsant action: Like other hydantoin derivatives, phenytoin stabilizes neuronal membranes and limits seizure activity by either increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. Phenytoin exerts its antiarrhythmic effects by normalizing sodium influx to Purkinje’s fibers in patients with cardiac glycoside-induced arrhythmias. It’s indicated for generalized tonic-clonic (grand mal) and partial seizures.
Other actions: Inhibits excessive collagenase activity in patients with epidermolysis bullosa.

Pharmacokinetics
Absorption: Absorbed slowly from small intestine; absorption is form-dependent and bioavailability may differ among products. I.M. doses absorbed erratically; about 50% to 75% of I.M. dose absorbed in 24 hours.
Distribution: Widely distributed throughout body; therapeutic plasma levels 10 to 20 mcg/ml; 5 to 10 mcg/ml in some patients. Lateral nystagmus may occur at levels above 20 mcg/ml; ataxia usually at levels above 30 mcg/ml; significantly decreased mental capacity at 40 mcg/ml. About 90% protein-bound; less so in uremic patients.
Metabolism: Metabolized by liver to inactive metabolites.
Excretion: Excreted in urine; exhibits dose-dependent (zero-order) elimination kinetics. Above a certain dosage level, small increases in dosage disproportionately increase serum levels.

Contraindications and precautions
Contraindicated in patients with hydantoin hypersensitivity, sinus bradycardia, SA block, second- or third-degree AV block, or Adams-Stokes syndrome.
  Use cautiously in elderly or debilitated patients; in those with hepatic dysfunction, hypotension, myocardial insufficiency, diabetes, or respiratory depression; and in those receiving hydantoin derivatives.

Interactions
Drug-drug. : Phenytoin interacts with many drugs. Diminished therapeutic effects and toxic reactions commonly are the result of recent changes in drug therapy.
Allopurinol, amiodarone, benzodiazepines, chloramphenicol, chlorpheniramine, cimetidine, diazepam, disulfiram, fluconazole, ibuprofen, imipramine, isoniazid, metronidazole, miconazole, omeprazole, phenacemide, phenylbutazone, salicylates, succinimides, trimethoprim, valproic acid: Increases therapeutic effects of phenytoin. Monitor patient.
Amiodarone, APAP, carbamazepine, corticosteroids, cyclosporine, dicumarol, digitoxin, disopyramide, dopamine, doxycycline, estrogens, furosemide, haloperidol, hormonal contraceptives, levodopa, mebendazole, meperidine, methadone, metyrapone, phenothiazines, quinidine, sulfonylureas: Decreases effects of these drugs via increased hepatic metabolism. Adjust dosages as needed.
Antacids, antineoplastics, barbiturates, calcium, calcium gluconate, carbamazepine, charcoal, diazoxide, folic acid, loxapine, nitrofurantoin, pyridoxine, rifampin, sucralfate, theophylline: Decreases therapeutic effects of phenytoin. Monitor patient.
Antipsychotic drugs: Lowers seizure threshold. Use together cautiously.
Lithium: Increases lithium toxicity. Monitor serum lithium levels.
Warfarin: May displace warfarin, resulting in increased PT and INR. Monitor PT and INR.
Drug-food. Enteral nutrition therapy: May reduce orally administered phenytoin levels. Consider administering phenytoin 2 hours before starting enteral feeding, or wait 2 hours after stopping enteral feeding to administer phenytoin.
Drug-lifestyle. Alcohol use: Decreases therapeutic effects. Discourage alcohol use.

Adverse reactions
CNS: ataxia, slurred speech, dizziness, insomnia, nervousness, twitching, headache, mental confusion, decreased coordination.
CV: periarteritis nodosa, hypotension.
EENT: nystagmus, diplopia, blurred vision.
GI: nausea, vomiting, constipation, gingival hyperplasia (especially in children).
Hematologic: thrombocytopenia, leukopenia, agranulocytosis, pancytopenia, macrocythemia, megaloblastic anemia.
Hepatic: toxic hepatitis.
Metabolic: hyperglycemia, decreased protein-bound iodine.
Musculoskeletal: osteomalacia.
Skin: scarlatiniform or morbilliform rash; bullous, exfoliative, or purpuric dermatitis; Stevens-Johnson syndrome; lupus erythematosus; hirsutism; toxic epidermal necrolysis; photosensitivity; pain, necrosis, and inflammation at injection site; discoloration of skin (purple glove syndrome) if given by I.V. push in back of hand.
Other: lymphadenopathy, hypertrichosis.

Effects on lab test results
• May increase alkaline phosphatase, GGT, and glucose levels.
• May decrease hemoglobin, hematocrit, and platelet, WBC, RBC, and granulocyte counts.

Overdose and treatment
Early toxicity may cause drowsiness, nausea, vomiting, nystagmus, ataxia, dysarthria, tremor, and slurred speech; then hypotension, arrhythmias, respiratory depression, and coma. Death is caused by respiratory and circulatory depression. Estimated lethal dose in adults is 2 to 5 g.
 Treat overdose with gastric lavage or emesis and follow with supportive treatment. Carefully monitor vital signs and fluid and electrolyte balance. Forced diuresis is of little or no value. Hemodialysis or peritoneal dialysis may be helpful.

Special considerations
• Only extended-release capsules are approved for once-daily dosing; all other forms are given in divided doses every 8 to 12 hours.
• Oral or nasogastric feeding may interfere with absorption of oral suspension; separate dosing and feeding times as much as possible, but by no less than 1 hour. During continuous tube feeding, tube should be flushed before and after dose.
• If suspension is used, shake well.
• I.M. administration should be avoided; it’s painful and drug absorption is erratic.
• Mix I.V. doses in normal saline solution and use within 30 minutes; mixtures with D₅W will precipitate. Don’t refrigerate solution; don’t mix with other drugs. In-line filter is recommended.
• If using I.V. bolus, use slow (50 mg/minute) I.V. push or constant infusion; too-rapid I.V. injection may cause hypotension and circulatory collapse. Don’t use I.V. push in veins on back of hand; larger veins are needed to prevent discoloration caused by purple glove syndrome.
• When giving I.V., monitor ECG, blood pressure, and respiratory status continuously.
• Monitoring of serum levels is essential because of dose-dependent excretion. • Abrupt withdrawal may precipitate status epilepticus.
• Phenytoin commonly is abbreviated as DPH (diphenylhydantoin), an older drug name.
• Drug may interfere with the 1-mg dexamethasone suppression test.
Breast-feeding patients
• Drug appears in breast milk. An alternative to breast-feeding is recommended during therapy.
Pediatric patients
• Special pediatric-strength suspension (30 mg/5 ml) is available in Canada only. Take extreme care to use correct strength. Don’t confuse with adult strength (125 mg/5 ml).
Geriatric patients
• Elderly patients metabolize and excrete drug slowly; they may require lower dosages.

Patient education
• Tell patient to use same brand of phenytoin consistently. Changing brands may change effect.
• Instruct patient to take drug with food or milk to minimize GI distress.
• Warn patient not to stop drug, except with medical supervision; to avoid hazardous activities that require alertness until CNS effect is determined; and to avoid alcoholic beverages, which can decrease effectiveness of drug and increase adverse reactions.
• Tell patient to notify provider if skin rash develops.
• Encourage patient to wear a medical identification bracelet or necklace.
• Stress good oral hygiene to minimize overgrowth and sensitivity of gums.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use