Phenytoin

Synonyms :
5,5-Diphenyl-imidazolidine-2,4-dione, 5,5-diphenylimidazolidine-2,4-dione, 5,5-diphenyltetrahydro-1H-2,4-imidazoledione, 5,5-Diphenyltetrahydro-1H-2,4-imidazoledione, DILANTIN, Fenitoina, PHENTYTOIN, Phenytoine, Phenytoinum

Status : approved

Category

Anticonvulsants

Therapeutic Classification

ANTIEPILEPTICS

NERVOUS SYSTEM
ANTIEPILEPTICS
ANTIEPILEPTICS
Voltage-Gated Sodium Channel Blockers

Description

An anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [PubChem]

Used

For the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.

Mechanism Of Action

Phenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.

Dosage

Form Route Strength
Capsule, extended release oral 100 mg
Capsule, extended release oral 30 mg
Capsule oral 30 mg
Tablet oral 50 mg
Tablet, chewable oral 50 mg
Liquid intramuscular; intravenous 250 mg
Capsule oral 100 mg
Suspension oral 125 mg/5mL
Suspension oral 125 mg
Suspension oral 30 mg
Capsule oral 100 mg
Capsule, extended release oral 200 mg
Capsule, extended release oral 300 mg
Suspension oral 100 mg/4mL
Injection intramuscular; intravenous 50 mg/mL
Injection intravenous 50 mg/mL
Injection, solution intramuscular; intravenous 250 mg/5mL
Injection, solution intramuscular; intravenous 50 mg/mL
Solution intramuscular; intravenous 50 mg
Liquid intramuscular; intravenous 50 mg

Pharmacodynamics

Phenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Phenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. Phenytoin acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells. It lacks the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilization, although it has never been approved for those purposes by the FDA. Phenytoin is primarily metabolized by CYP2C9.

Toxic Effect

Oral, mouse: LD50 = 150 mg/kg; Oral, rat: LD50 = 1635 mg/kg. Symptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting.

Metabolism

Primarily hepatic. The majority of the dose (up to 90%) is metabolized to 5-(4′-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This metabolite undergoes further glucuronidation and is excreted into the urine. CYP2C19 and CYP2C9 catalyze the aforementioned reaction.

Absorption

Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.

Half Life

22 hours (range of 7 to 42 hours)

Protein Binding

Highly protein bound, 90%

Elimination Route

Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion.

Chemical Classification

This compound belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.

Phenylhydantoins

Organic compounds

Organoheterocyclic compounds

Azolidines

Imidazolidines

Salt : Phenytoin Sodium

Chemical Name

5,5-Diphenyl-imidazolidine-2,4-dione

Brands

name Dosage form Country
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin tablet, chewable US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule, extended release US
Dilantin capsule US
Dilantin capsule, extended release US
Dilantin – 100mg capsule Canada
Dilantin – 30mg capsule Canada
Dilantin Infatabs tablet, chewable US
Dilantin Infatabs tablet, chewable US
Dilantin Infatabs tablet Canada
Dilantin Inj 50mg/ml liquid Canada
Dilantin W Phenobarbital 15mg capsule Canada
Dilantin W Phenobarbital 30mg Cap capsule Canada
Dilantin-125 suspension US
Dilantin-125 Suspension suspension Canada
Dilantin-30 Suspension suspension Canada
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule, extended release US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Extended Phenytoin Sodium capsule US
Novo-phenytoin Cap 100mg capsule Canada
Phenytek capsule, extended release US
Phenytek capsule, extended release US
Phenytek capsule, extended release US
Phenytoin tablet, chewable US
Phenytoin suspension US
Phenytoin suspension US
Phenytoin tablet, chewable US
Phenytoin tablet, chewable US
Phenytoin suspension US
Phenytoin suspension US
Phenytoin suspension US
Phenytoin suspension US
Phenytoin suspension US
Phenytoin tablet, chewable US
Phenytoin suspension US
Phenytoin tablet, chewable US
Phenytoin suspension US
Phenytoin tablet, chewable US
Phenytoin suspension US
Phenytoin ER capsule US
Phenytoin Infatabs tablet, chewable US
Phenytoin Sodium injection US
Phenytoin Sodium injection US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection, solution US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection US
Phenytoin Sodium injection US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection US
Phenytoin Sodium injection, solution US
Phenytoin Sodium injection US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium injection, solution US
Phenytoin Sodium capsule, extended release US
Phenytoin Sodium Inj 50mg/ml USP solution Canada
Phenytoin Sodium Injection USP liquid Canada
Phenytoin Sodium Injection, USP solution Canada
Taro-phenytoin suspension Canada
Tremytoine Inj 50mg/ml liquid Canada

Drug Drug Interactions

  •  Abiraterone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Abiraterone Acetate.
  •  Acenocoumarol  : May enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Phenytoin.
  •  Acetaminophen  : Fosphenytoin-Phenytoin may decrease the serum concentration of Acetaminophen. Specifically, serum concentrations of acetaminophen may be decreased (leading to decreased efficacy), but the formation of the toxic N-acetyl-p-benzoquinone imine (NAPQI) metabolite may be increased (leading to increased hepatotoxicity).
  •  Acetazolamide  : May enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased.
  •  Afatinib  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Afatinib.
  •  Albendazole  : Phenytoin may decrease serum concentrations of the active metabolite(s) of Albendazole.
  •  Aminophylline  : May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Phenytoin.
  •  Amiodarone  : Phenytoin may decrease the serum concentration of Amiodarone. Amiodarone may increase the serum concentration of Phenytoin.
  •  Amlodipine  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Amphetamine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Amrinone  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Apixaban  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban.
  •  Apremilast  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast.
  •  Aripiprazole  : CYP3A4 Inducers may decrease the serum concentration of Aripiprazole.
  •  Artemether  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Artemether. Specifically, dihydroartemisinin concentrations may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Artemether.
  •  Atorvastatin  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Axitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
  •  Bazedoxifene  : Phenytoin may decrease the serum concentration of Bazedoxifene. This may lead to loss of efficacy or, if bazedoxifene is combined with estrogen therapy, an increased risk of endometrial hyperplasia.
  •  Bedaquiline  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline.
  •  Bepridil  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Bleomycin  : May decrease the serum concentration of Phenytoin.
  •  Boceprevir  : Phenytoin may decrease the serum concentration of Boceprevir.
  •  Bortezomib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib.
  •  Bosutinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib.
  •  Brentuximab vedotin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased.
  •  Brentuximab vedotin  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased.
  •  Brexpiprazole  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Brexpiprazole.
  •  Bromazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Bumetanide  : May diminish the diuretic effect of Loop Diuretics.
  •  Buprenorphine  : CNS Depressants may enhance the CNS depressant effect of Buprenorphine.
  •  Busulfan  : Phenytoin may decrease the serum concentration of Busulfan.
  •  Cabozantinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib.
  •  Camazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Canagliflozin  : Phenytoin may decrease the serum concentration of Canagliflozin.
  •  Cannabidiol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Cannabidiol.
  •  Capecitabine  : May increase the serum concentration of Phenytoin.
  •  Carbamazepine  : May decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Carbamazepine. Carbamazepine may increase the serum concentration of Phenytoin. Possibly by competitive inhibition at sites of metabolism.
  •  Caspofungin  : Inducers of Drug Clearance may decrease the serum concentration of Caspofungin.
  •  Cathinone  : May decrease the serum concentration of Phenytoin.
  •  Cefazolin  : May decrease the protein binding of Phenytoin.
  •  Ceritinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ceritinib.
  •  Chlordiazepoxide  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Chlormezanone  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Chlorphenamine  : May increase the serum concentration of Fosphenytoin-Phenytoin.
  •  Cimetidine  : May enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Cimetidine may increase the serum concentration of Fosphenytoin-Phenytoin.
  •  Cinolazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Ciprofloxacin  : Ciprofloxacin (Systemic) may diminish the therapeutic effect of Phenytoin. Ciprofloxacin (Systemic) may decrease the serum concentration of Phenytoin.
  •  Clarithromycin  : CYP3A4 Inducers (Strong) may increase serum concentrations of the active metabolite(s) of Clarithromycin. Clarithromycin may increase the serum concentration of CYP3A4 Inducers (Strong). CYP3A4 Inducers (Strong) may decrease the serum concentration of Clarithromycin.
  •  Clobazam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Clonazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Clotiazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Cloxazolam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Clozapine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Clozapine.
  •  Cobicistat  : Fosphenytoin-Phenytoin may decrease the serum concentration of Cobicistat.
  •  Colesevelam  : May decrease the serum concentration of Phenytoin.
  •  Cosyntropin  : May enhance the hepatotoxic effect of Phenytoin.
  •  Crizotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib.
  •  Cyclosporine  : May increase the metabolism of Cyclosporine (Systemic).
  •  Dabigatran etexilate  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran etexilate.
  •  Dabrafenib  : May decrease the serum concentration of CYP2C9 Substrates.
  •  Dabrafenib  : May decrease the serum concentration of CYP2C19 Substrates.
  •  Daclatasvir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Daclatasvir.
  •  Darunavir  : May decrease the serum concentration of Phenytoin.
  •  Dasatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib.
  •  Deferasirox  : Phenytoin may decrease the serum concentration of Deferasirox.
  •  Delavirdine  : Phenytoin may decrease the serum concentration of Delavirdine. Delavirdine may increase the serum concentration of Phenytoin.
  •  Desogestrel  : May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
  •  Desogestrel  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Dexamethasone  : May decrease the serum concentration of Dexamethasone (Systemic). Dexamethasone (Systemic) may decrease the serum concentration of Phenytoin. Dexamethasone (Systemic) may increase the serum concentration of Phenytoin.
  •  Dexmethylphenidate  : May increase the serum concentration of Phenytoin.
  •  Dextroamphetamine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Diazoxide  : May decrease the serum concentration of Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations.
  •  Diclofenamide  : May enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased.
  •  Dienogest  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dienogest.
  •  Diltiazem  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Disopyramide  : Phenytoin may decrease the serum concentration of Disopyramide.
  •  Disulfiram  : May increase the serum concentration of Phenytoin.
  •  Dolutegravir  : Fosphenytoin-Phenytoin may decrease the serum concentration of Dolutegravir.
  •  Doxycycline  : Phenytoin may decrease the serum concentration of Doxycycline.
  •  Doxylamine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronabinol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tetrahydrocannabinol.
  •  Dronabinol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Dronedarone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone.
  •  Droperidol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Drospirenone  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Efavirenz  : Phenytoin may decrease the serum concentration of Efavirenz. Efavirenz may increase the serum concentration of Phenytoin.
  •  Eliglustat  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat.
  •  Elvitegravir  : Fosphenytoin-Phenytoin may decrease the serum concentration of Elvitegravir.
  •  Enzalutamide  : CYP2C8 Inducers (Strong) may decrease the serum concentration of Enzalutamide.
  •  Enzalutamide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Enzalutamide.
  •  Enzalutamide  : May decrease the serum concentration of Fosphenytoin-Phenytoin.
  •  Erlotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib.
  •  Eslicarbazepine acetate  : May decrease the serum concentration of Eslicarbazepine. Eslicarbazepine may increase the serum concentration of Phenytoin.
  •  Estazolam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Ethacrynic acid  : May diminish the diuretic effect of Loop Diuretics.
  •  Ethinyl Estradiol  : May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
  •  Ethinyl Estradiol  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Ethosuximide  : May enhance the CNS depressant effect of Phenytoin. Phenytoin may decrease the serum concentration of Ethosuximide. Ethosuximide may increase the serum concentration of Phenytoin.
  •  Ethoxzolamide  : May enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased.
  •  Ethynodiol  : May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
  •  Ethynodiol  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Etonogestrel  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Etoposide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide.
  •  Etoposide  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Etoposide Phosphate.
  •  Etravirine  : Phenytoin may decrease the serum concentration of Etravirine.
  •  Everolimus  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus.
  •  Exemestane  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane.
  •  Ezogabine  : Fosphenytoin-Phenytoin may decrease the serum concentration of Ezogabine.
  •  Felbamate  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Felbamate.
  •  Felodipine  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Fentanyl  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Fentanyl.
  •  Flibanserin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Flibanserin.
  •  Floxuridine  : May increase the serum concentration of Phenytoin.
  •  Fluconazole  : May increase the serum concentration of Phenytoin.
  •  Fludiazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Flunarizine  : Phenytoin may decrease the serum concentration of Flunarizine.
  •  Flunitrazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Fluorouracil  : Fluorouracil (Systemic) may increase the serum concentration of Phenytoin.
  •  Fluoxetine  : May increase the serum concentration of Phenytoin.
  •  Fluvastatin  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Fluvoxamine  : May increase the serum concentration of Phenytoin.
  •  Folic Acid  : May decrease the serum concentration of Phenytoin.
  •  Fosamprenavir  : May decrease the serum concentration of Phenytoin. The active amprenavir metabolite is likely responsible for this effect. Phenytoin may increase the serum concentration of Fosamprenavir. Specifically, phenytoin may increase the concentration of the active metabolite amprenavir.
  •  Furosemide  : May diminish the diuretic effect of Loop Diuretics.
  •  Gabapentin  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Gefitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib.
  •  Guanfacine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Guanfacine.
  •  Halazepam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Halothane  : May increase the serum concentration of Phenytoin.
  •  Hydrocodone  : CNS Depressants may enhance the CNS depressant effect of Hydrocodone.
  •  Hydroxyzine  : May enhance the CNS depressant effect of CNS Depressants.
  •  Ibrutinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ibrutinib.
  •  Idelalisib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Idelalisib.
  •  Imatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib.
  •  Irinotecan  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Irinotecan. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan.
  •  Isavuconazonium  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Isavuconazonium Sulfate. Specifically, CYP3A4 Inducers (Strong) may decrease isavuconazole serum concentrations.
  •  Isoniazid  : May increase the serum concentration of Phenytoin.
  •  Isradipine  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Itraconazole  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole.
  •  Ivabradine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivabradine.
  •  Ivacaftor  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor.
  •  Ixabepilone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone.
  •  Ketazolam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Ketoconazole  : Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic).
  •  Lacosamide  : Phenytoin may decrease the serum concentration of Lacosamide.
  •  Lamotrigine  : Phenytoin may decrease the serum concentration of Lamotrigine.
  •  Lapatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib.
  •  Ledipasvir  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Ledipasvir.
  •  Lercanidipine  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Leucovorin  : Leucovorin Calcium-Levoleucovorin may decrease the serum concentration of Phenytoin.
  •  Levodopa  : Phenytoin may diminish the therapeutic effect of Levodopa.
  •  Levonorgestrel  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Levothyroxine  : May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
  •  Linagliptin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin.
  •  Linagliptin  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Linagliptin.
  •  Liothyronine  : May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
  •  Liotrix  : May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
  •  Lisdexamfetamine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Lithium  : Phenytoin may enhance the adverse/toxic effect of Lithium.
  •  Lopinavir  : Phenytoin may decrease the serum concentration of Lopinavir. Lopinavir may decrease the serum concentration of Phenytoin.
  •  Lorazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Lovastatin  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Luliconazole  : May increase the serum concentration of CYP2C19 Substrates.
  •  Lumefantrine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine.
  •  Lurasidone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone.
  •  MACITENTAN  : CYP3A4 Inducers (Strong) may decrease the serum concentration of MACITENTAN.
  •  Magnesium Sulfate  : May enhance the CNS depressant effect of CNS Depressants.
  •  Maraviroc  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
  •  Mebendazole  : Phenytoin may decrease the serum concentration of Mebendazole.
  •  Medroxyprogesterone Acetate  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Mefloquine  : May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants.
  •  Mestranol  : May diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
  •  Mestranol  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Methadone  : Phenytoin may decrease the serum concentration of Methadone.
  •  Methamphetamine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Methotrexate  : May decrease the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may increase the serum concentration of Methotrexate. Specifically, fosphenytoin-phenytoin may displace methotrexate from serum proteins, increasing the concentration of free, unbound drug.
  •  Methotrimeprazine  : CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.
  •  Methylphenidate  : May increase the serum concentration of Phenytoin.
  •  Methylprednisolone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Methylprednisolone.
  •  Metronidazole  : May decrease the serum concentration of Metronidazole (Systemic). Metronidazole (Systemic) may increase the serum concentration of Phenytoin.
  •  Metyrapone  : Phenytoin may decrease the serum concentration of Metyrapone. The oral metyrapone test would thus be unreliable unless the metapyrone dosage was substantially increased (e.g., 750 mg every 2 hours).
  •  Metyrosine  : CNS Depressants may enhance the sedative effect of Metyrosine.
  •  Mexiletine  : Phenytoin may decrease the serum concentration of Mexiletine.
  •  Mianserin  : May diminish the therapeutic effect of Phenytoin. Phenytoin may decrease the serum concentration of Mianserin.
  •  Miconazole  : Miconazole (Oral) may increase the serum concentration of Phenytoin.
  •  Mifepristone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Mifepristone.
  •  Minocycline  : May enhance the CNS depressant effect of CNS Depressants.
  •  Nabilone  : May enhance the CNS depressant effect of CNS Depressants.
  •  Naloxegol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Naloxegol.
  •  Nelfinavir  : May decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Nelfinavir.
  •  Netupitant  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Netupitant.
  •  Nicardipine  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Nifedipine  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Nifedipine.
  •  Nilotinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
  •  Nimodipine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nimodipine.
  •  Nintedanib  : Combined Inducers of CYP3A4 and P-glycoprotein may decrease the serum concentration of Nintedanib.
  •  Nisoldipine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Nisoldipine.
  •  Nitrazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Nitrendipine  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Nitric Oxide  : May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Norethindrone  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Norgestimate  : May diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
  •  Olaparib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Olaparib.
  •  Omeprazole  : Phenytoin may decrease the serum concentration of Omeprazole. Omeprazole may increase the serum concentration of Phenytoin.
  •  Orlistat  : May decrease the serum concentration of Anticonvulsants.
  •  Orphenadrine  : CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
  •  Oxazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Oxcarbazepine  : Fosphenytoin-Phenytoin may decrease serum concentrations of the active metabolite(s) of Oxcarbazepine. Specifically, concentrations of the major active 10-monohydroxy metabolite may be reduced. Oxcarbazepine may increase the serum concentration of Fosphenytoin-Phenytoin.
  •  Palbociclib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Palbociclib.
  •  Paliperidone  : Inducers of CYP3A4 (Strong) and P-glycoprotein may decrease the serum concentration of Paliperidone.
  •  Panobinostat  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat.
  •  Paraldehyde  : CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
  •  Pazopanib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Pazopanib.
  •  Perampanel  : Phenytoin may decrease the serum concentration of Perampanel.
  •  Perhexiline  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Pethidine  : Phenytoin may decrease the serum concentration of Meperidine.
  •  Phendimetrazine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Phenobarbital  : Phenytoin may enhance the CNS depressant effect of Phenobarbital. Phenobarbital may decrease the serum concentration of Phenytoin. Phenytoin may increase the serum concentration of Phenobarbital.
  •  Phentermine  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Ponatinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ponatinib.
  •  Posaconazole  : Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic).
  •  Pramipexole  : CNS Depressants may enhance the sedative effect of Pramipexole.
  •  Pravastatin  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Praziquantel  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel.
  •  Prednisone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Prednisone.
  •  Prenylamine  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Prilocaine  : Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Primidone  : Phenytoin may increase the metabolism of Primidone. The ratio of primidone:phenobarbital is thus changed.
  •  Propafenone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Propafenone.
  •  Pyridoxine  : May increase the metabolism of Phenytoin. This is most apparent in high Pyridoxine doses (e.g., 80 mg to 200 mg daily)
  •  Quazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Quetiapine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Quetiapine.
  •  Quinidine  : Phenytoin may decrease the serum concentration of Quinidine.
  •  Quinine  : Phenytoin may decrease the serum concentration of Quinine.
  •  Ranolazine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine.
  •  Regorafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib.
  •  Rifampicin  : May decrease the serum concentration of Phenytoin.
  •  Rilpivirine  : Phenytoin may decrease the serum concentration of Rilpivirine.
  •  Risedronate  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Ritonavir  : Phenytoin may decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Phenytoin.
  •  Rivaroxaban  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban.
  •  Roflumilast  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast.
  •  Romidepsin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Romidepsin.
  •  Ropinirole  : CNS Depressants may enhance the sedative effect of Ropinirole.
  •  Rotigotine  : CNS Depressants may enhance the sedative effect of Rotigotine.
  •  Rufinamide  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Rufinamide.
  •  Saxagliptin  : CYP3A4 Inducers may decrease the serum concentration of Saxagliptin.
  •  Sertraline  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Sertraline.
  •  Simeprevir  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
  •  Simvastatin  : May decrease the serum concentration of HMG-CoA Reductase Inhibitors.
  •  Sirolimus  : Phenytoin may decrease the serum concentration of Sirolimus.
  •  Sodium Nitrite  : Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
  •  Sodium oxybate  : May enhance the CNS depressant effect of CNS Depressants.
  •  Sofosbuvir  : P-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Sofosbuvir.
  •  Sonidegib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sonidegib.
  •  Sorafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sorafenib.
  •  Stiripentol  : May decrease the serum concentration of Phenytoin.
  •  Sulfamethoxazole  : May increase the serum concentration of Phenytoin.
  •  Sunitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Sunitinib.
  •  Suvorexant  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant.
  •  Tacrolimus  : May decrease the serum concentration of Tacrolimus (Systemic). Tacrolimus (Systemic) may increase the serum concentration of Phenytoin.
  •  Tadalafil  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil.
  •  Tapentadol  : May enhance the CNS depressant effect of CNS Depressants.
  •  Tasimelteon  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tasimelteon.
  •  Telaprevir  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Telaprevir.
  •  Temazepam  : Benzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Temsirolimus  : Phenytoin may decrease the serum concentration of Temsirolimus. Concentrations of the active metabolite, sirolimus, are also likely to be decreased (and maybe to an even greater degree).
  •  Teniposide  : Phenytoin may decrease the serum concentration of Teniposide.
  •  Thalidomide  : CNS Depressants may enhance the CNS depressant effect of Thalidomide.
  •  Theophylline  : May decrease the serum concentration of Theophylline Derivatives. Theophylline Derivatives may decrease the serum concentration of Phenytoin.
  •  Thyroid extract  : May decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
  •  Ticagrelor  : CYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor.
  •  Ticlopidine  : May increase the serum concentration of Phenytoin.
  •  Tipranavir  : Phenytoin may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Phenytoin.
  •  Tofacitinib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib.
  •  Tofisopam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Tolvaptan  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan.
  •  Topiramate  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Topiramate.
  •  Topotecan  : Fosphenytoin-Phenytoin may decrease the serum concentration of Topotecan.
  •  Toremifene  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene.
  •  Trabectedin  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin.
  •  Trazodone  : Phenytoin may decrease the serum concentration of Trazodone. Trazodone may increase the serum concentration of Phenytoin.
  •  Treprostinil  : CYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil.
  •  Triazolam  : May increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
  •  Trimethoprim  : May increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Trimethoprim.
  •  Ulipristal  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal.
  •  Vandetanib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib.
  •  Vemurafenib  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib.
  •  Verapamil  : Calcium Channel Blockers may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Calcium Channel Blockers.
  •  Vigabatrin  : May decrease the serum concentration of Phenytoin.
  •  Vilazodone  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone.
  •  Vincristine  : Phenytoin may decrease the serum concentration of Vincristine. Vincristine may decrease the serum concentration of Phenytoin.
  •  Vindesine  : May decrease the serum concentration of Phenytoin.
  •  Vorapaxar  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar.
  •  Voriconazole  : Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs. Phenytoin may decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic).
  •  Vortioxetine  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Vortioxetine.
  •  Warfarin  : May enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Phenytoin.
  •  Zaleplon  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Zaleplon.
  •  Zolpidem  : CNS Depressants may enhance the CNS depressant effect of Zolpidem.
  •  Zonisamide  : Phenytoin may decrease the serum concentration of Zonisamide.
  •  Zuclopenthixol  : CYP3A4 Inducers (Strong) may decrease the serum concentration of Zuclopenthixol.

Food Interactions

  • Avoid alcohol., Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication., Take with food to increase bioavailability and reduce irritation.

Calculated Property

kind Value Source
logP 2.26 ALOGPS
logS -3.5 ALOGPS
Water Solubility 7.11e-02 g/l ALOGPS
logP 2.15 ChemAxon
IUPAC Name 5,5-diphenylimidazolidine-2,4-dione ChemAxon
Traditional IUPAC Name silantin ChemAxon
Molecular Weight 252.268 ChemAxon
Monoisotopic Weight 252.089877638 ChemAxon
SMILES O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1 ChemAxon
Molecular Formula C15H12N2O2 ChemAxon
InChI InChI=1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19) ChemAxon
InChIKey InChIKey=CXOFVDLJLONNDW-UHFFFAOYSA-N ChemAxon
Polar Surface Area (PSA) 58.2 ChemAxon
Refractivity 70.18 ChemAxon
Polarizability 25.48 ChemAxon
Rotatable Bond Count 2 ChemAxon
H Bond Acceptor Count 2 ChemAxon
H Bond Donor Count 2 ChemAxon
pKa (strongest acidic) 9.47 ChemAxon
pKa (strongest basic) -9 ChemAxon
Physiological Charge 0 ChemAxon
Number of Rings 3 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 1 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Sodium channel protein type 5 subunit alpha : in Human
  • Sodium channel protein type 1 subunit alpha : in Human