Phenytoin
Pronouncation: (FEN-ih-toe-in)Class: Hydantoin Phenytoin
Trade Names:
Dilantin Infatab
- Tablets, chewable 50 mg
Trade Names:
Dilantin-125
- Suspension, oral 125 mg/5 mL
Trade Names:
Dilantin
- Injection 50 mg/mL (46 mg phenytoin)
Trade Names:
Dilantin Kapseals
- Capsules 30 mg (27.6 mg phenytoin)
- Capsules 100 mg (92 mg phenytoin)
Pharmacology
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Feedback for Phenytoin
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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.
Pharmacokinetics
Absorption
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 12ߙh ( Kapseals ); 1.5 to 3 h ( Infatabs , Dilantin-125 oral suspension).
Distribution
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%).
Metabolism
Hydroxylated in the liver by an enzyme system, which is saturable at high plasma levels.
Elimination
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 h (oral phenytoin) and 14 h ( 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.
Contraindications
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.
SeizuresAdults
PO 100 mg (or 125 mg of suspension) 3 times daily initially.
Maintenance300 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-h intervals. Once seizure control is established, extended-release form (300 mg) may be administered for once-a-day dosing.
ChildrenPO 5 mg/kg/day in 2 to 3 divided doses initially.
Maintenance4 to 8 mg/kg/day (max, 300 mg/day).
Status EpilepticusAdults
IV Loading dose of 10 to 15 mg/kg via slow IV. Then PO/IV 100 mg every 6 to 8 h.
ChildrenIV Loading dose of 15 to 20ߙmg/kg at rate not exceeding 1 to 3 mg/kg/min.
Neurosurgery ProphylaxisAdults
IM 100 to 200 mg at 4-h 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
AcetaminophenMay increase hepatotoxicity potential with chronic phenytoin use.
Amiodarone, chloramphenicol, disulfiram, estrogens, felbamate, fluconazole, isoniazid, cimetidine, trimethoprim, phenylbutazone, oxyphenbutazone, phenacemide, sulfonamidesMay increase phenytoin serum levels.
Carbamazepine, sucralfate, antineoplastic agents, rifampin, rifabutinMay decrease phenytoin serum levels.
Corticosteroids, coumarin anticoagulants, doxycycline, estrogens, levodopa, felodipine, methadone, loop diuretics, oral contraceptives, quinidine, rifampin, rifabutinMay impair effects of these agents.
CyclosporineMay reduce cyclosporine levels.
DisopyramideMay cause decreased disopyramide levels and bioavailability and may enhance anticholinergic actions.
Enteral nutritional therapyMay reduce phenytoin concentrations.
Folic acidMay cause folic acid deficiency.
MetyraponePhenytoin may cause subnormal response to metyrapone.
MexiletineMay decrease mexiletine levels and effects.
Nondepolarizing muscle relaxantsMay cause these agents to have shorter duration or decreased effects.
Phenobarbital, sodium valproate, valproic acidMay increase or decrease phenytoin levels. Phenytoin may increase phenobarbital and decrease valproic acid levels.
PrimidoneMay increase concentrations of primidone and metabolites.
Sympathomimetics (eg, dopamine)May cause profound hypotension and possibly cardiac arrest.
TheophyllinesEffects of either agent may be decreased.
Incompatibility
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
Cardiovascular
CV collapse, hypotension, atrial and ventricular conduction depression, ventricular fibrillation (IV use).
CNS
Nystagmus; ataxia; dysarthria; slurred speech; mental confusion; dizziness; insomnia; transient nervousness; motor twitching; diplopia; fatigue; irritability; drowsiness; depression; numbness; tremor; headache; choreoathetosis (IV use).
Dermatologic
Rashes, sometimes accompanied by fever; bullous, exfoliative or purpuric dermatitis; lupus erythematosus; Stevens-Johnson syndrome; toxic epidermal necrolysis; hirsutism; alopecia.
EENT
Conjunctivitis.
GI
Nausea; vomiting; diarrhea; constipation.
Hematologic
Thrombocytopenia; leukopenia; granulocytopenia; agranulocytosis; pancytopenia; macrocytosis; megaloblastic anemia; eosinophilia; monocytosis; leukocytosis; simple anemia; hemolytic anemia; aplastic anemia.
Hepatic
Toxic hepatitis and liver damage; hepatocellular degeneration and necrosis; hepatitis; jaundice; nephrosis.
Miscellaneous
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.
Precautions
Pregnancy
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.
Lactation
Excreted in breast milk.
Hypersensitivity
Rapid substitution of alternate therapy may be necessary.
Special Risk Patients
Use drug with caution with hepatic function impairment, acute intermittent porphyria, alcohol abuse, hypotension, and severe myocardial insufficiency.
Bioavailability
Because products vary in bioavailability; brand interchange is not recommended.
Seizures
Drug should not be given to treat seizures due to hypoglycemia or other metabolic causes or petit mal (absence) epilepsy.
Withdrawal
Abrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually.
Overdosage
Symptoms
Nystagmus, ataxia, dysarthria, hypotension, diminished mental capacity, coma, unresponsive pupils, respiratory and CV 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 medical identification (eg, card, bracelet) 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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More Phenytoin resources:
Dilantin Kapseals Extended-Release Capsules
Dilantin Infatabs Chewable Tablets
Phenytoin - Includes detailed dosage instructions.
Anxiety, Seizures, Epilepsy, Arrhythmia, Trigeminal Neuralgia, Status Epilepticus











