Control of generalized tonic-clonic and complex partial (psychomotor, temporal lobe) seizures; prevention and treatment of seizures occurring during or after neurosurgery (excludes oral suspension); control of tonic-clonic type of status epilepticus (parenteral administration).
Individualize dose within clinically effective therapeutic serum level of 10 to 20 mcg/mL.
Adults: PO 100 mg (or 125 mg of suspension) 3 times daily initially.
Maintenance: 300 to 400 mg/day. An increase to 600 mg/day (625 mg/day of suspension) may be made if necessary. 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, ER form (300 mg) may be administered for once-daily dosing.
Children: PO 5 mg/kg/day in 2 to 3 divided doses initially.
Maintenance: 4 to 8 mg/kg/day (max, 300 mg/day).
Adults: IV Loading dose of 10 to 15 mg/kg via slow IV, not exceeding 50 mg/min. Then PO/IV 100 mg every 6 to 8 h.
Children: IV Loading dose of 15 to 20 mg/kg at rate not exceeding 1 to 3 mg/kg/min.
Adults: IM 100 to 200 mg at 4-h intervals during surgery and postoperatively.
Appears to act at the motor cortex by inhibiting the spread of seizure activity. Possibly works by promoting sodium efflux from neurons, thereby stabilizing threshold against hyperexcitability. Also decreases posttetanic potentiation at synapses.
Hypersensitivity to phenytoin or other hydantoins; Adams-Stokes syndrome, second- and third-degree AV block, sinoatrial block, sinus bradycardia (injection only).
CV: Atrial and ventricular conduction depression, CV collapse, hypotension; ventricular fibrillation (IV use).
CNS: Asterixis, ataxia, chorea, decreased coordination, dizziness, dystonia, headache, insomnia, mental confusion, motor twitching, nystagmus, sensory peripheral neuropathy, slurred speech, transient nervousness, tremor; CNS depression (IV use).
DERM: Bullous, exfoliative, or purpuric dermatitis; hypertrichosis; lupus erythematosus; morbilliform or scarlatiniform rashes, sometimes accompanied by fever; Stevens-Johnson syndrome; TEN.
GI: Constipation, nausea, vomiting.
HEMA: Agranulocytosis, benign lymph node hyperplasia, granulocytopenia, Hodgkin disease, immunoglobulin abnormalities, leukopenia, lymphoma, macrocytosis, megaloblastic anemia, pancytopenia with or without bone marrow suppression, pseudolymphoma, thrombocytopenia.
HEPA: Liver damage, toxic hepatitis.
HYPERSEN: Anticonvulsant hypersensitivity syndrome, including symptoms such as arthralgias, eosinophilia, fever, liver dysfunction, lymphadenopathy, or rash.
LOCAL: Inflammation, local irritation, necrosis, sloughing; tenderness (IV use).
OTHER: Coarsening of facial features, gingival hyperplasia, lip enlargement, periarteritis nodosa, Peyronie disease, SLE.
The potential hepatotoxicity of acetaminophen may be increased when long-term doses of hydantoins are coadministered. The therapeutic effects of acetaminophen may be reduced with simultaneous phenytoin therapy.
Acute alcohol ingestion may increase phenytoin plasma levels, while long-term use may decrease plasma concentrations. Monitor phenytoin plasma concentrations and adjust the phenytoin dose as needed.
Increased serum phenytoin concentrations with symptoms of toxicity. Phenytoin may decrease amiodarone serum levels. Monitor drug concentrations and observe patients for phenytoin toxicity or loss of amiodarone therapeutic effect when this combination is used. Adjust the dose of either drug as needed.
Antacids (containing calcium), molindone
Calcium ions may interfere with phenytoin absorption. In patients with low serum phenytoin levels, stagger ingestion times of orally administered phenytoin and antacid preparations containing calcium to prevent absorption problems. The commercial molindone products contain calcium ions that interfere with the absorption of phenytoin.
Anticoagulants (eg, warfarin)
Increased phenytoin serum concentrations with possible toxicity. Increased and decreased PT/INR responses have been reported. May increase or decrease the anticoagulant effect of warfarin. Monitor the response of the patient and adjust the dose of either drug as needed.
Antineoplastic agents (eg, bleomycin), chloral hydrate, ciprofloxacin, corticosteroids, diazoxide, enteral nutrition therapy, folic acid, reserpine, sirolimus, sucralfate, vigabatrin
Phenytoin serum concentrations may be reduced, decreasing the efficacy. Monitor phenytoin serum levels and adjust the phenytoin dose appropriately.
Azole antifungal agents (eg, itraconazole)
Phenytoin plasma levels may be elevated, increasing the risk of toxicity, while itraconazole, ketoconazole, and voriconazole plasma levels may be reduced, decreasing efficacy. If coadministration cannot be avoided, monitor phenytoin plasma concentrations and observe the clinical response of the patient. Adjust the dose of either drug as needed.
The effect of barbiturates on hydantoins is unpredictable. Phenobarbital may either increase or decrease plasma phenytoin concentrations. The addition of phenytoin may increase barbiturate serum concentrations. Monitor serum concentrations of both drugs, seizure activity, and clinical symptoms when initiating or discontinuing either drug. Adjust treatment as needed.
Benzodiazepines (eg, midazolam), cimetidine, disulfiram, erlotinib, estrogens, fluconazole, fluorouracil, fluoxetine, fluvoxamine, halothane, isoniazid, methylphenidate, omeprazole, phenacemide, salicylates (eg, aspirin), sertraline, succinimides (eg, ethosuximide), sulfonamides (eg, sulfadiazine), ticlopidine, trazodone, trimethoprim
Phenytoin serum concentrations may be elevated, increasing the pharmacologic effects and the risk of toxicity. Monitor phenytoin concentrations and observe the clinical response of the patient. Adjust the phenytoin dose as needed.
The effect of carbamazepine on phenytoin is variable. Phenytoin decreases serum carbamazepine levels. Monitor serum concentrations of both drugs, particularly when starting or stopping either drug. Adjust the dose of carbamazepine and/or phenytoin as needed.
Increased serum phenytoin concentrations with potential toxicity. Chloramphenicol concentrations may be increased or decreased. Measure concentrations of both drugs and observe the patient for signs of phenytoin toxicity. Adjust the dose of either drug as needed.
Colesevelam may bind to and impair oral absorption of oral phenytoin. Administer phenytoin 4 h prior to colesevelam. Measure phenytoin concentrations and adjust the dose as needed.
Cyclosporine concentrations may be decreased, resulting in a decrease in the immunosuppressive activity of cyclosporine, which may predispose patients to transplant rejection. Measure cyclosporine concentrations and monitor for evidence of transplant rejection. Adjust the cyclosporine dose as needed.
Digoxin, doxycycline, everolimus, felodipine, gefitinib, haloperidol, imatinib, irinotecan, ixabepilone, levodopa, loop diuretics (eg, furosemide), maraviroc, methadone, mexiletine, mirtazapine, nisoldipine, praziquantel, quetiapine, quinidine, temsirolimus, teniposide, tolvaptan, vitamin D
The effects of these agents may be impaired. Monitor for a decrease in therapeutic effect and increase the dose of these agents as needed.
Disopyramide concentrations and bioavailability may be decreased, while anticholinergic actions may be enhanced. Monitor the response of the patient and adjust the disopyramide dose as needed.
Dronedarone, NNRTIs (eg, etravirine), tyrosine kinase receptor inhibitors (eg, dasatinib, lapatinib, nilotinib)
Plasma concentrations of these agents may be reduced by phenytoin, decreasing the pharmacologic effects. Avoid coadministration.
Phenytoin concentrations may be elevated, increasing the pharmacologic effect and risk of adverse reactions. Efavirenz plasma concentrations may be reduced, decreasing the pharmacologic effects. Monitor concentrations of both drugs and observe the patient response. Adjust the dose of efavirenz and/or phenytoin as needed.
Phenytoin concentrations may be elevated, increasing the pharmacologic effect and risk of adverse reactions. Measure phenytoin concentrations and monitor the patient’s response when starting, stopping, or changing the erlotinib dose. Erlotinib plasma concentrations may be reduced, decreasing the pharmacologic effects. If alternate treatment lacking CYP3A4 activity is not available, consider increasing the erlotinib starting dose at 2 wk intervals. If the dose is adjusted upward, reduce the erlotinib dose to the indicated erlotinib starting dose immediately after stopping phenytoin.
Estrogens (eg, conjugated estrogens, ethinyl estradiol), hormonal contraceptives, progestins (eg, levonorgestrel, norgestrel)
Phenytoin levels may be increased by estrogens or hormonal contraceptives. Pharmacologic effects of estrogens, hormonal contraceptives, and progestins may be decreased. Alternative or nonhormonal contraception is recommended during hydantoin therapy. Also, monitor phenytoin concentrations and observe the clinical response of the patient. Adjust the phenytoin dose as needed.
Exemestane plasma concentrations may be reduced, decreasing the pharmacologic effects. The recommended dosage of exemestane is 50 mg once daily after a meal if phenytoin is coadministered. If phenytoin is discontinued, reduce the exemestane dosage to 25 mg once daily with a meal.
Serum phenytoin concentrations may be increased, possibly resulting in an increase in the pharmacologic and toxic effects of phenytoin. Phenytoin may also decrease felbamate concentrations. Monitor phenytoin and felbamate concentrations, and observe patients for changes in seizure control. Adjust the dose of either drug as needed.
The anticonvulsant effects of phenytoin may be altered by food. Administer phenytoin consistently with respect to meals in order to avoid fluctuations in the amount of phenytoin absorbed. In patients receiving continuous tube feedings, higher doses of phenytoin may be necessary. Monitor phenytoin plasma concentrations, and adjust the dose as needed.
HMG-CoA reductase inhibitors (eg, atorvastatin, simvastatin)
HMG-CoA reductase inhibitor concentrations may be reduced, decreasing the pharmacologic effect. Monitor the clinical response of the patient. If an interaction is suspected, consider administering alternative therapy. Pravastatin may be less likely to interact.
Phenytoin may cause subnormal response to metyrapone. Consider using oral metyrapone doses of as much as twice the usual amount.
Nondepolarizing muscle relaxants (eg, cisatracurium, pancuronium, vecuronium)
Nondepolarizing muscle relaxants may have a shorter than expected duration of action or be less effective. Nondepolarizing muscle relaxant dosages may need to be increased. Monitor for reduced effectiveness.
Phenothiazines (eg, fluphenazine, prochlorperazine, thioridazine)
An increase in the pharmacologic effects of phenytoin and a decrease in the effectiveness of thioridazine may be observed. Measure phenytoin concentrations and monitor the patient for signs of toxicity. Adjust the phenytoin dose as needed.
May increase concentrations of primidone and primidone metabolites, increasing the effects. Closely monitor primidone and primidone metabolites and the patient’s response following any alteration in phenytoin therapy. Adjust the primidone dose as needed.
Protease inhibitors (eg, lopinavir/ritonavir)
Certain protease inhibitors and phenytoin plasma concentrations may be reduced during coadministration, decreasing the therapeutic effects of both drugs. Measure phenytoin concentrations. Adjust the dose of phenytoin or lopinavir/ritonavir as needed.
Serum levels of ranolazine may be reduced, decreasing the pharmacologic effects. Avoid coadministration.
Rifamycins (eg, rifabutin, rifampin)
Serum phenytoin levels may be decreased, resulting in a possible decrease in the pharmacologic effects of phenytoin. Phenytoin may impair efficacy of rifampin. Measure phenytoin concentrations and observe the response of the patient when rifabutin or rifampin is started or stopped. Adjust the phenytoin dose as needed. An increased rifampin dosage may be necessary.
Sodium valproate, valproic acid
Coadministration may either increase or decrease phenytoin plasma concentrations, while those of valproic acid may be decreased. Phenytoin toxicity may occur at therapeutic total plasma concentrations. Monitor the levels of the free concentrations of phenytoin and serum valproic acid levels. Adjust dose of either drug as needed.
Sympathomimetics (eg, dopamine)
May cause profound hypotension and, possibly, cardiac arrest. Use phenytoin with extreme caution.
Tacrolimus serum concentrations may be reduced, decreasing the efficacy, while phenytoin concentrations may be elevated, increasing the pharmacologic effects and adverse reactions. Monitor serum concentrations of both tacrolimus and phenytoin. Adjust the dose of phenytoin or tacrolimus as needed.
Effects of either agent may be decreased. When either medication is added to or removed from a patient’s regimen, monitor plasma levels of each drug and adjust the doses as needed.
Serum phenytoin levels may be increased. Measure phenytoin concentrations. If an interaction is suspected, adjust the phenytoin dose as needed. Phenytoin may cause an increase in blood glucose levels, necessitating a higher dose of sulfonylurea for control of hyperglycemia.
Topiramate may increase the effects of phenytoin, while phenytoin may decrease the pharmacologic effects of topiramate. Measure phenytoin concentrations and observe the response of the patient when topiramate is started or stopped. Adjust the phenytoin dose as needed. A decreased topiramate dose may be needed when phenytoin is stopped after concurrent use.
Tricyclic antidepressants (eg, amitriptyline)
May precipitate seizures, necessitating phenytoin dosage adjustments. The pharmacologic effects of phenytoin may be elevated, increasing the pharmacologic effects and risk of toxicity. Measure phenytoin concentrations and observe the response of the patient when a tricyclic antidepressant is started or stopped. If an interaction is suspected, adjust the phenytoin dose as needed.
Therapeutic Classification: antiarrhythmics (group IB), anticonvulsants
Pharmacologic Classification: hydantoins
Absorption: Absorbed slowly from the GI tract. Bioavailability differs among products; the Dilantin and Phenytek preparations are considered to be “extended” products. Other products are considered to be prompt release.
Distribution: Distributes into CSF and other body tissues and fluids. Enters breast milk; crosses the placenta, achieving similar maternal/fetal levels. Preferentially distributes into fatty tissue.
Protein Binding: Adults 90–95%; decreased protein binding in neonates (up to 20% free fraction available), infants (up to 15% free), and patients with hyperbilirubinemia, hypoalbuminemia, severe renal dysfunction or uremia.
Metabolism/Excretion: Mostly metabolized by the liver; minimal amounts excreted in the urine.
Half-life: 22 hr (range 7–42 hr).
|ORAL||2-24 HOUR||1.5-3 HOUR||6-12 HOUR|
|ORAL-ER||2-24 HOUR||4-12 HOUR||12-36 HOUR|
|INTRAVENOUS||0.5-1 HOUR||RAPID||12-24 HOUR|
time required for onset of action without a loading dose