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All about: Phenytoin

Big Image Pronouncation: (FEN-ih-toe-in)
Class: Hydantoin Phenytoin

Trade Names:
Dilantin Infatab
- Tablets, chewable 50 mg

Trade Names:
- Suspension, oral 125 mg/5 mL

Phenytoin Sodium

Trade Names:
- Injection 50 mg/mL (46 mg phenytoin)

Trade Names:
Dilantin Kapseals
- Capsules 30 mg (27.6 mg phenytoin)
- Capsules 100 mg (92 mg phenytoin)

Dilantin-30 Pediatric (Canada)

Mechanism of Action


Appears to act at motor cortex in inhibiting spread of seizure activity. Possibly works by promoting sodium efflux from neurons, thereby stabilizing threshold against hyperexcitability. Also decreases posttetanic potentiation at synapse.



Slow and variable (oral); poor in neonates; rapid (IV); slow but complete (IM). Steady state is 7 to 10 days. T max is 4 to 12 hr ( Kapseals ); 1.5 to 3 hr ( Infatabs , Dilantin-125 oral suspension).


Distributes into CSF, saliva, semen, GI fluids, bile, breast milk, and crosses the placenta. Protein binding is high (more than 90%) but may be lower in neonates (84%).


Hydroxylated in the liver by an enzyme system, which is saturable at high plasma levels.


Mostly excreted in bile as inactive metabolites, then reabsorbed from the intestinal tract and excreted in the urine (as metabolites). Plasma t 1/2 is 22 hr (oral phenytoin) and 14 hr ( Infatabs ). Excretion is enhanced by alkaline urine.

Indications and Usage

Control of grand mal and psychomotor seizures; prevention and treatment of seizures occurring during or after neurosurgery; control of grand mal type of status epilepticus (parenteral administration).

Unlabeled Uses

Control of arrhythmias, (particularly cardiac glycoside-induced arrhythmias); control of convulsions in severe preeclampsia; treatment of trigeminal neuralgia (tic douloureux), recessive dystrophic epidermolysis bullosa and junctional epidermolysis bullosa.


Hypersensitivity to phenytoin or other hydantoins; sinoatrial block; sinus bradycardia; second- and third-degree atrioventricular block; Adams-Stokes syndrome.

Dosage and Administration

Individualize dose within clinically effective therapeutic serum level of 10 to 20 mcg/mL.


PO 100 mg (or 125 mg of suspension) tid initially.


300 to 400 mg/day (max, 600 mg/day). Sometimes initial 1 g loading dose is divided into 3 doses (400, 300, and 300 mg) and is given at 2-hr intervals. Once seizure control is established, extended-release form (300 mg) may be administered for once-a-day dosing.


PO 5 mg/kg/day in 2 to 3 divided doses initially.


4 to 8 mg/kg/day (max, 300 mg/day).

Status Epilepticus

IV Loading dose of 10 to 15 mg/kg via slow IV. Then PO/IV 100 mg q 6 to 8 hr.


IV Loading dose of 15 to 20 mg/kg at rate not exceeding 1 to 3 mg/kg/min.

Neurosurgery Prophylaxis

IM 100 to 200 mg at 4-hr intervals during surgery and postoperatively.

General Advice

  • Shake oral suspension well.
  • Do not administer discolored capsules.
  • Only extended-release capsules are recommended for once-a-day dosage.
  • Do not crush or allow patient to chew extended-release capsules.
  • For parenteral administration, direct IV administration is recommended.
  • Administer IV into large vein via large-gauge needle or cannula. Do not exceed rate of 50 mg/min for adults or 1 to 3 mg/kg/min in newborns. Immediately flush with normal saline solution. Avoid continuous infusion.
  • Avoid IM route when possible. If IM administration is needed for greater than 1 wk, consider alternatives such as gastric intubation.
  • When patient is stabilized with oral phenytoin and switched from oral to IM route, dose must be increased by 50%. When patient returns to oral form after IM administration, 1/ 2 original oral dose should be given for 1 wk.
  • Do not use parenteral solution if precipitates form that will not dissolve at room temperature.
  • Do not use parenteral solution if it is hazy; faint, clear yellow color is acceptable for use.

Drug Interactions


May increase hepatotoxicity potential with chronic phenytoin use.

Amiodarone, chloramphenicol, disulfiram, estrogens, felbamate, fluconazole, isoniazid, cimetidine, trimethoprim, phenylbutazone, oxyphenbutazone, phenacemide, sulfonamides

May increase phenytoin serum levels.

Carbamazepine, sucralfate, antineoplastic agents, rifampin, rifabutin

May decrease phenytoin serum levels.

Corticosteroids, coumarin anticoagulants, doxycycline, estrogens, levodopa, felodipine, methadone, loop diuretics, oral contraceptives, quinidine, rifampin, rifabutin

May impair effects of these agents.


May reduce cyclosporine levels.


May cause decreased disopyramide levels and bioavailability and may enhance anticholinergic actions.

Enteral nutritional therapy

May reduce phenytoin concentrations.

Folic acid

May cause folic acid deficiency.


Phenytoin may cause subnormal response to metyrapone.


May decrease mexiletine levels and effects.

Nondepolarizing muscle relaxants

May cause these agents to have shorter duration or decreased effects.

Phenobarbital, sodium valproate, valproic acid

May increase or decrease phenytoin levels. Phenytoin may increase phenobarbital and decrease valproic acid levels.


May increase concentrations of primidone and metabolites.

Sympathomimetics (eg, dopamine)

May cause profound hypotension and possibly cardiac arrest.


Effects of either agent may be decreased.


Do not mix with other drugs in syringe.

Laboratory Test Interactions

Phenytoin may interfere with metapyrone and dexamethasone tests, causing inaccurate results because of increased metabolism of these agents. Drug may cause decreases in serum levels of protein-bound iodine. It may cause increased levels of glucose, alkaline phosphatase and gamma glutamyl transpeptidase.

Adverse Reactions


CV collapse, hypotension, atrial and ventricular conduction depression, ventricular fibrillation (IV use).


Nystagmus; ataxia; dysarthria; slurred speech; mental confusion; dizziness; insomnia; transient nervousness; motor twitching; diplopia; fatigue; irritability; drowsiness; depression; numbness; tremor; headache; choreoathetosis (IV use).


Rashes, sometimes accompanied by fever; bullous, exfoliative or purpuric dermatitis; lupus erythematosus; Stevens-Johnson syndrome; toxic epidermal necrolysis; hirsutism; alopecia.




Nausea; vomiting; diarrhea; constipation.


Thrombocytopenia; leukopenia; granulocytopenia; agranulocytosis; pancytopenia; macrocytosis; megaloblastic anemia; eosinophilia; monocytosis; leukocytosis; simple anemia; hemolytic anemia; aplastic anemia.


Toxic hepatitis and liver damage; hepatocellular degeneration and necrosis; hepatitis; jaundice; nephrosis.


Gingival hyperplasia; coarsening of facial features; lip enlargement; Peyronie's disease; polyarthropathy; hyperglycemia; weight gain; chest pain; IgA depression; fever; photophobia; gynecomastia; periarteritis nodosa; pulmonary fibrosis; tissue injury at injection site; lymph node hyperplasia; hypothyroidism.



Pregnancy category undetermined. Consult health care provider. Possible risk of birth defects must be considered along with risk of seizures to fetus in untreated epileptic mothers.


Excreted in breast milk.


Rapid substitution of alternate therapy may be necessary.

Special Risk Patients

Use drug with caution with hepatic impairment, acute intermittent porphyria, alcohol abuse, hypotension, and severe myocardial insufficiency.


Because products vary in bioavailability; brand interchange is not recommended.


Drug should not be given to treat seizures due to hypoglycemia or other metabolic causes or petit mal (absence) epilepsy.


Abrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually.



Nystagmus, ataxia, dysarthria, hypotension, diminished mental capacity, coma, unresponsive pupils, respiratory and cardiovascular depression.

Patient Information

  • Advise patient to take medication with food.
  • Teach patient to shake oral suspension well.
  • Instruct patient taking capsules not to use discolored ones.
  • Tell patient to notify health care provider if skin rash develops.
  • Instruct patient to report the following symptoms to health care provider: nystagmus, ataxia, drowsiness, severe nausea or vomiting, gingival hyperplasia, or jaundice.
  • Caution patient to consult with health care provider before using alcohol or taking any other drug including OTC medications.
  • Warn patient that stopping medication too quickly may precipitate seizures. Stress that dose should be changed only under health care provider's direction.
  • Inform patient that it is important to maintain good oral hygiene and to inform dentist of phenytoin therapy.
  • Instruct diabetic patient that changes may occur in blood sugars and to monitor and report any abnormal results to health care provider.
  • Inform patient that urine may turn pink.
  • Advise patient to carry identification such as Medi-Alert that identifies illness and medication.
  • Warn patient to inform surgeon, health care provider, or dentist about this medication before any surgical, emergency, or dental procedure.
  • Advise patient that drug may cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness.

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