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Identification
NamePhenytoin
Accession NumberDB00252  (APRD00241)
TypeSmall Molecule
GroupsApproved
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]

Structure
Thumb
Synonyms
SynonymLanguageCode
5,5-Diphenyl-imidazolidine-2,4-dioneNot AvailableNot Available
5,5-diphenylimidazolidine-2,4-dioneNot AvailableNot Available
5,5-diphenyltetrahydro-1H-2,4-imidazoledione Not AvailableNot Available
5,5-Diphenyltetrahydro-1H-2,4-imidazoledioneNot AvailableNot Available
DILANTINNot AvailableNot Available
FenitoinaSpanishINN
PHENTYTOINNot AvailableNot Available
PhenytoineFrenchINN
PhenytoinumLatinINN
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dilantin-125suspension125 mg/5mLoralParke Davis Div Of Pfizer Inc1953-01-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralGreenstone LLC2012-10-09Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dilantin Infatabstablet, chewable50 mgoralParke Davis Div Of Pfizer Inc1979-02-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralParke Davis Div Of Pfizer Inc1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralParke Davis Div Of Pfizer Inc1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralKAISER FOUNDATION HOSPITALS2009-09-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralMylan Pharmaceuticals Inc.1999-01-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytekcapsule, extended release200 mgoralMylan Pharmaceuticals Inc.2001-12-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytekcapsule, extended release300 mgoralMylan Pharmaceuticals Inc.2001-12-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytointablet, chewable50 mgoralMylan Pharmaceuticals Inc.2012-12-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousHospira, Inc.1987-03-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousHospira, Inc.2011-02-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralActavis Mid Atlantic LLC2009-03-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralNcs Health Care Of Ky, Inc Dba Vangard Labs2009-11-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintramuscular; intravenousWest Ward Pharmaceutical Corp.1975-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintramuscular; intravenousWest Ward Pharmaceutical Corp.1975-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintramuscular; intravenousWest Ward Pharmaceutical Corp.1975-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintramuscular; intravenousWest Ward Pharmaceutical Corp.1975-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralUpsher Smith Laboratories, Inc.2006-09-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralAtlantic Biologicals Corps2002-06-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralAtlantic Biologicals Corps2004-04-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralRebel Distributors Corp2006-09-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousX Gen Pharmaceuticals, Inc.2011-05-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralAphena Pharma Solutions Tennessee, Inc.1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralREMEDYREPACK INC.2010-11-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralREMEDYREPACK INC.2011-05-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule100 mgoralREMEDYREPACK INC.2011-07-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantintablet, chewable50 mgoralREMEDYREPACK INC.2011-08-18Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralLake Erie Medical DBA Quality Care Products LLC2006-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralA S Medication Solutions Llc1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytointablet, chewable50 mgoralMylan Institutional Inc.2013-02-15Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralMylan Institutional Inc.2012-09-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralTaro Pharmaceuticals U.S.A., Inc.2004-04-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralTaro Pharmaceuticals U.S.A., Inc.2006-09-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytointablet, chewable50 goralTaro Pharmaceuticals U.S.A., Inc2014-04-17Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralREMEDYREPACK INC.2013-03-20Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralREMEDYREPACK INC.2013-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousGeneral Injectables & Vaccines, Inc2010-08-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousGeneral Injectables & Vaccines, Inc2010-03-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution250 mg/5mLintramuscular; intravenousGeneral Injectables & Vaccines, Inc.2011-08-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousGeneral Injectables & Vaccines, Inc2010-08-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousGeneral Injectables & Vaccines, Inc2011-04-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralState of Florida DOH Central Pharmacy2009-07-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralA S Medication Solutions Llc1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralPhysicians Total Care, Inc.1995-01-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralPhysicians Total Care, Inc.2003-08-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralPhysicians Total Care, Inc.2006-12-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralPhysicians Total Care, Inc.2007-07-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantin Infatabstablet, chewable50 mgoralCardinal Health1979-02-26Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release100 mgoralCardinal Health1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralCardinal Health2006-09-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection, solution50 mg/mLintramuscular; intravenousCardinal Health2011-05-02Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintramuscular; intravenousCardinal Health1975-07-16Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralCardinal Health2011-01-28Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintravenousCardinal Health2006-10-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiuminjection50 mg/mLintravenousCardinal Health2006-10-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralClinical Solutions Wholesale2006-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytekcapsule, extended release300 mgoralClinical Solutions Wholesale2001-12-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Infatabstablet, chewable50 mgoralGreenstone LLC2012-12-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralMorton Grove Pharmaceuticals, Inc.2002-06-24Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule100 mgoralDIRECT RX2014-01-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release200 mgoralSun Pharmaceutical Industries Limited2008-06-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralSun Pharmaceutical Industries Limited2006-12-12Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release300 mgoralSun Pharmaceutical Industries Limited2008-06-30Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralbryant ranch prepack2011-07-07Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytointablet, chewable50 mgoralCore Pharma, Llc2014-12-08Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralTYA Pharmaceuticals2006-09-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralLehigh Valley Technologies, Inc.2014-04-01Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension125 mg/5mLoralVista Pharm Inc.2010-05-10Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralContract Pharmacy Services Pa2010-04-06Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoinsuspension100 mg/4mLoralPrecision Dose Inc.2004-02-05Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Dilantincapsule, extended release30 mgoralCarilion Materials Management1976-08-27Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Phenytoin Sodiumcapsule, extended release100 mgoralMc Kesson Contract Packaging2011-09-19Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Over the Counter ProductsNot Available
International Brands
NameCompany
Epanutin Pfizer
EptoinNot Available
Brand mixtures
Brand NameIngredients
Dilantin W Phenobarbital 15mgPhenobarbital + Phenytoin Sodium
Dilantin W Phenobarbital 30mg CapPhenobarbital + Phenytoin Sodium
Salts
Name/CASStructureProperties
Phenytoin Sodium
Thumb
  • InChI Key: FJPYVLNWWICYDW-UHFFFAOYSA-M
  • Monoisotopic Mass: 274.071822281
  • Average Mass: 274.2498
DBSALT000139
Categories
CAS number57-41-0
WeightAverage: 252.268
Monoisotopic: 252.089877638
Chemical FormulaC15H12N2O2
InChI KeyCXOFVDLJLONNDW-UHFFFAOYSA-N
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)
IUPAC Name
5,5-diphenylimidazolidine-2,4-dione
SMILES
O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassImidazolidines
Direct ParentPhenylhydantoins
Alternative Parents
Substituents
  • 5-phenylhydantoin
  • Diphenylmethane
  • Phenylimidazolidine
  • 5-monosubstituted hydantoin
  • Ureide
  • Benzenoid
  • Monocyclic benzene moiety
  • Urea
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Pharmacology
IndicationFor 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.
PharmacodynamicsPhenytoin 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.
Mechanism of actionPhenytoin 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.
AbsorptionBioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.
Volume of distributionNot Available
Protein bindingHighly protein bound, 90%
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.

SubstrateEnzymesProduct
Phenytoin
3',4'-DihydrodiolDetails
Phenytoin
3'-HPPHDetails
Phenytoin
4'-HPPHDetails
Phenytoin
Phenytoin arene-oxideDetails
Phenytoin
Not Available
Phenytoin catecholDetails
Phenytoin
Not Available
Phenytoin quinoneDetails
Phenytoin catechol
Phenytoin methylcatecholDetails
Phenytoin arene-oxide
Phenytoin dihydrodiolDetails
Phenytoin arene-oxide
Not Available
HydroxyphenytoinDetails
Hydroxyphenytoin
Phenytoin catecholDetails
Phenytoin catechol
Phenytoin quinoneDetails
Hydroxyphenytoin
Hydroxyphenytoin-O-glucuronideDetails
3'-HPPH
3',4'-diHPPHDetails
4'-HPPH
3',4'-diHPPHDetails
Route of eliminationMost 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.
Half life22 hours (range of 7 to 42 hours)
ClearanceNot Available
ToxicityOral, 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.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712
rs1057910 CYP2C9*1C AllelePoor drug metabolizer, lower dose requirements15805193
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs1045642 MDR1*TT Allele (C3435T)Increased phenytoin effects due to higher plasma phenytoin levels11908757
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9909
Blood Brain Barrier+0.976
Caco-2 permeable+0.8867
P-glycoprotein substrateNon-substrate0.5593
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.987
Renal organic cation transporterNon-inhibitor0.8995
CYP450 2C9 substrateNon-substrate0.733
CYP450 2D6 substrateSubstrate0.8911
CYP450 3A4 substrateNon-substrate0.7591
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.8304
CYP450 2D6 substrateNon-inhibitor0.935
CYP450 2C19 substrateNon-inhibitor0.9026
CYP450 3A4 substrateNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8994
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.855
BiodegradationNot ready biodegradable0.992
Rat acute toxicity2.1567 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9793
hERG inhibition (predictor II)Non-inhibitor0.8916
Pharmacoeconomics
Manufacturers
  • Parke davis div warner lambert co
  • Actavis mid atlantic llc
  • Taro pharmaceutical industries ltd
  • Vistapharm inc
  • Wockhardt eu operations (swiss) ag
  • Pfizer pharmaceuticals ltd
  • Lannett co inc
  • Amneal pharmaceuticals ny llc
  • Barr laboratories inc
  • Mylan pharmaceuticals inc
  • Pliva inc
  • Sun pharmaceutical industries ltd
  • Wockhardt ltd
  • Wockhardt usa inc
  • Watson laboratories inc
  • Pharmeral inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Parke davis pharmaceutical research div warner lambert co
  • App pharmaceuticals llc
  • Baxter healthcare corp
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Marsam pharmaceuticals llc
  • Pharmaforce inc
  • Smith and nephew solopak div smith and nephew
  • Solopak medical products inc
  • Warner chilcott div warner lambert co
Packagers
Dosage forms
FormRouteStrength
Capsuleoral100 mg
Capsule, extended releaseoral100 mg
Capsule, extended releaseoral200 mg
Capsule, extended releaseoral30 mg
Capsule, extended releaseoral300 mg
Injectionintramuscular; intravenous50 mg/mL
Injectionintravenous50 mg/mL
Injection, solutionintramuscular; intravenous250 mg/5mL
Injection, solutionintramuscular; intravenous50 mg/mL
Suspensionoral100 mg/4mL
Suspensionoral125 mg/5mL
Tablet, chewableoral50 g
Tablet, chewableoral50 mg
Prices
Unit descriptionCostUnit
Dilantin 125 mg/5ml Suspension 237ml Bottle69.28USD bottle
Phenytoin Sodium 50 mg/ml2.64USD ml
Phenytek 300 mg capsule1.47USD capsule
Phenytoin sod ext 300 mg capsule1.2USD capsule
Phenytoin sodium powder1.16USD g
Phenytek 200 mg capsule0.98USD capsule
Phenytoin 50 mg/ml ampul0.96USD ml
Phenytoin sod ext 200 mg capsule0.8USD capsule
Phenytoin 50 mg/ml vial0.67USD ml
Phenytoin 100 mg/2 ml vial0.6USD ml
Dilantin Infatabs 50 mg Chew Tabs0.6USD tab
Dilantin 100 mg capsule0.51USD capsule
Phenytoin 100 mg/4 ml susp0.48USD ml
Dilantin 30 mg capsule0.46USD capsule
Phenytoin 250 mg/5 ml vial0.45USD ml
Dilantin 50 mg infatab0.44USD each
Dilantin 100 mg kapseal0.39USD each
Dilantin 30 mg kapseal0.39USD each
Phenytoin Sodium Extended 100 mg capsule0.36USD capsule
Phenytoin sod ext 100 mg capsule0.34USD capsule
Phenytoin powder0.23USD g
Phenytoin 125 mg/5ml Suspension0.15USD ml
Dilantin Infatabs 50 mg Chewable Tablet0.08USD tablet
Dilantin 100 mg Capsule0.08USD capsule
Dilantin 30 mg Capsule0.06USD capsule
Dilantin-125 25 mg/ml Suspension0.05USD ml
Dilantin-30 6 mg/ml Suspension0.04USD ml
Taro-Phenytoin 25 mg/ml Suspension0.03USD ml
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PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point286 °CPhysProp
water solubility32 mg/L (at 22 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.47HANSCH,C ET AL. (1995)
Caco2 permeability-4.57ADME Research, USCD
pKa8.33SANGSTER (1994)
Predicted Properties
PropertyValueSource
Water Solubility0.0711 mg/mLALOGPS
logP2.26ALOGPS
logP2.15ChemAxon
logS-3.5ALOGPS
pKa (Strongest Acidic)9.47ChemAxon
pKa (Strongest Basic)-9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity70.18 m3·mol-1ChemAxon
Polarizability25.48 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (9.46 KB)
SpectraMS1D NMR
References
Synthesis Reference

Mahdi B. Fawzi, Anne K. Taylor, “Parenteral phenytoin preparations.” U.S. Patent US4642316, issued April, 1981.

US4642316
General Reference
  1. https://www.pharmgkb.org/pathway/PA145011115
External Links
ATC CodesN03AB02
AHFS Codes
  • 28:12.12
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73.7 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolMay enhance the anticoagulant effect of Vitamin K Antagonists. Vitamin K Antagonists may increase the serum concentration of Phenytoin.
AcetaminophenFosphenytoin-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).
AcetazolamideMay enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Exceptions: Brinzolamide; Dorzolamide.
AfatinibP-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Afatinib.
AlbendazolePhenytoin may decrease serum concentrations of the active metabolite(s) of Albendazole.
AlprazolamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
AminophyllineTheophylline Derivatives may decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Theophylline Derivatives.
AmiodaroneMay increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Amiodarone.
AmlodipineMay increase the serum concentration of Phenytoin.
AmphetamineAmphetamines may decrease the serum concentration of Phenytoin.
AmrinoneMay increase the serum concentration of Phenytoin.
ApixabanCYP3A4 Inducers (Strong) may decrease the serum concentration of Apixaban.
ApremilastCYP3A4 Inducers (Strong) may decrease the serum concentration of Apremilast.
AripiprazoleCYP3A4 Inducers may decrease the serum concentration of ARIPiprazole.
ArtemetherCYP3A4 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.
AtorvastatinMay decrease the serum concentration of HMG-CoA Reductase Inhibitors.
AxitinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Axitinib.
bazedoxifenePhenytoin 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.
BedaquilineCYP3A4 Inducers (Strong) may decrease the serum concentration of Bedaquiline.
BepridilMay increase the serum concentration of Phenytoin.
BleomycinMay decrease the serum concentration of Phenytoin.
BoceprevirPhenytoin may decrease the serum concentration of Boceprevir.
BortezomibCYP3A4 Inducers (Strong) may decrease the serum concentration of Bortezomib.
BosutinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Bosutinib.
Brentuximab vedotinCYP3A4 Inducers (Strong) may decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased.
BromazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
BumetanideMay diminish the diuretic effect of Loop Diuretics.
BuprenorphineCNS Depressants may enhance the CNS depressant effect of Buprenorphine.
BusulfanPhenytoin may decrease the serum concentration of Busulfan.
CabozantinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Cabozantinib.
CamazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
CanagliflozinPhenytoin may decrease the serum concentration of Canagliflozin.
CapecitabineMay increase the serum concentration of Phenytoin.
CarbamazepineMay decrease the serum concentration of Phenytoin. CarBAMazepine may increase the serum concentration of Phenytoin. Possibly by competitive inhibition at sites of metabolism. Phenytoin may decrease the serum concentration of CarBAMazepine.
CaspofunginInducers of Drug Clearance may decrease the serum concentration of Caspofungin.
CathinoneMay decrease the serum concentration of Phenytoin.
CefazolinMay decrease the protein binding of Phenytoin.
ChlordiazepoxideMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
ChlormezanoneMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
CimetidineMay enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Cimetidine may increase the serum concentration of Fosphenytoin-Phenytoin.
CinolazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
ClarithromycinCYP3A4 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.
ClobazamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
ClonazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
ClotiazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
CloxazolamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
ClozapineCYP3A4 Inducers (Strong) may decrease the serum concentration of CloZAPine.
ColesevelamMay decrease the serum concentration of Phenytoin.
CosyntropinMay enhance the hepatotoxic effect of Phenytoin.
CrizotinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Crizotinib.
Dabigatran etexilateP-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Dabigatran Etexilate.
DabrafenibMay decrease the serum concentration of CYP2C9 Substrates.
DarunavirMay decrease the serum concentration of Phenytoin.
DasatinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Dasatinib.
DeferasiroxPhenytoin may decrease the serum concentration of Deferasirox.
DelavirdineMay increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Delavirdine.
DesogestrelMay diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
DexmethylphenidateMay increase the serum concentration of Phenytoin.
DextroamphetamineAmphetamines may decrease the serum concentration of Phenytoin.
DiazoxideMay decrease the serum concentration of Phenytoin. Total phenytoin concentrations may be affected more than free phenytoin concentrations.
DiclofenamideMay enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Exceptions: Brinzolamide; Dorzolamide.
DiltiazemCalcium Channel Blockers may increase the serum concentration of Phenytoin.
DisopyramidePhenytoin may decrease the serum concentration of Disopyramide.
DisulfiramMay increase the serum concentration of Phenytoin.
DolutegravirFosphenytoin-Phenytoin may decrease the serum concentration of Dolutegravir.
DoxycyclinePhenytoin may decrease the serum concentration of Doxycycline.
DoxylamineMay enhance the CNS depressant effect of CNS Depressants.
DronabinolCYP3A4 Inducers (Strong) may decrease the serum concentration of Dronabinol.
DronedaroneCYP3A4 Inducers (Strong) may decrease the serum concentration of Dronedarone.
DroperidolMay enhance the CNS depressant effect of CNS Depressants.
DrospirenoneMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
EfavirenzMay increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Efavirenz.
EliglustatCYP3A4 Inducers (Strong) may decrease the serum concentration of Eliglustat.
EnzalutamideCYP2C8 Inducers (Strong) may decrease the serum concentration of Enzalutamide.
ErlotinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Erlotinib.
EstazolamBenzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
Ethacrynic acidMay diminish the diuretic effect of Loop Diuretics.
EthanolAlcohol (Ethyl) may enhance the CNS depressant effect of Phenytoin. Alcohol (Ethyl) may increase the serum concentration of Phenytoin. This may be particularly applicable with acute, heavy alcohol consumption. Alcohol (Ethyl) may decrease the serum concentration of Phenytoin. This may be particularly applicable with chronic, heavy alcohol consumption.
Ethinyl EstradiolMay diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
EthosuximideMay enhance the CNS depressant effect of Phenytoin. Ethosuximide may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Ethosuximide.
EthoxzolamideMay enhance the adverse/toxic effect of Fosphenytoin-Phenytoin. Specifically, the risk for osteomalacia or rickets may be increased. Exceptions: Brinzolamide; Dorzolamide.
EthynodiolMay diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
EtonogestrelMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
EtoposidePhenytoin may decrease the serum concentration of Etoposide.
EtravirinePhenytoin may decrease the serum concentration of Etravirine.
EverolimusCYP3A4 Inducers (Strong) may decrease the serum concentration of Everolimus.
ExemestaneCYP3A4 Inducers (Strong) may decrease the serum concentration of Exemestane.
EzogabinePhenytoin may decrease the serum concentration of Ezogabine.
FelbamateMay increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Felbamate.
FelodipineMay increase the serum concentration of Phenytoin.
FentanylCYP3A4 Inducers (Strong) may decrease the serum concentration of FentaNYL.
FloxuridineMay increase the serum concentration of Phenytoin.
FluconazoleFluconazole may increase the serum concentration of Phenytoin.
FludiazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
FlunarizineMay increase the serum concentration of Phenytoin.
FlunitrazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
FluoxetineMay increase the serum concentration of Phenytoin.
FluvastatinMay decrease the serum concentration of HMG-CoA Reductase Inhibitors.
FluvoxamineFluvoxaMINE may increase the serum concentration of Phenytoin.
Folic AcidFolic Acid may decrease the serum concentration of Phenytoin.
FosamprenavirMay 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.
FurosemideMay diminish the diuretic effect of Loop Diuretics.
GabapentinMay increase the serum concentration of Phenytoin.
GefitinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Gefitinib.
GuanfacineCYP3A4 Inducers (Strong) may decrease the serum concentration of GuanFACINE.
HalazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
HalothaneMay increase the serum concentration of Phenytoin.
HydrocodoneCNS Depressants may enhance the CNS depressant effect of Hydrocodone.
HydroxyzineMay enhance the CNS depressant effect of CNS Depressants.
ImatinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Imatinib.
IrinotecanCYP3A4 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.
IsoniazidMay increase the serum concentration of Phenytoin.
IsradipineMay increase the serum concentration of Phenytoin.
ItraconazoleCYP3A4 Inducers (Strong) may decrease the serum concentration of Itraconazole.
IvacaftorCYP3A4 Inducers (Strong) may decrease the serum concentration of Ivacaftor.
IxabepiloneCYP3A4 Inducers (Strong) may decrease the serum concentration of Ixabepilone.
KetazolamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
LacosamidePhenytoin may decrease the serum concentration of Lacosamide.
LamotrigineMay increase the serum concentration of Phenytoin.
LapatinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Lapatinib.
LedipasvirP-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Ledipasvir.
LercanidipineMay increase the serum concentration of Phenytoin.
LevonorgestrelMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
LevothyroxineMay decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
LinagliptinCYP3A4 Inducers (Strong) may decrease the serum concentration of Linagliptin.
LiothyronineMay decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
LiotrixMay decrease the serum concentration of Thyroid Products. Phenytoin may also displace thyroid hormones from protein binding sites.
LisdexamfetamineAmphetamines may decrease the serum concentration of Phenytoin.
LithiumPhenytoin may enhance the adverse/toxic effect of Lithium.
LopinavirMay decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Lopinavir.
LorazepamBenzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
LovastatinMay decrease the serum concentration of HMG-CoA Reductase Inhibitors.
LULICONAZOLEMay increase the serum concentration of CYP2C19 Substrates.
LumefantrineCYP3A4 Inducers (Strong) may decrease the serum concentration of Lumefantrine.
LurasidoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Lurasidone.
MACITENTANCYP3A4 Inducers (Strong) may decrease the serum concentration of Macitentan.
Magnesium SulfateMay increase the serum concentration of Phenytoin.
MaravirocCYP3A4 Inducers (Strong) may decrease the serum concentration of Maraviroc.
MebendazolePhenytoin may decrease the serum concentration of Mebendazole.
Medroxyprogesterone AcetateMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
MefloquineMay diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants.
MestranolMay diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
MethadonePhenytoin may decrease the serum concentration of Methadone.
MethamphetamineAmphetamines may decrease the serum concentration of Phenytoin.
MethotrexateMay 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.
MethotrimeprazineCNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants.
MethylphenidateMay increase the serum concentration of Phenytoin.
MethylprednisoloneCYP3A4 Inducers (Strong) may decrease the serum concentration of MethylPREDNISolone.
MetyraponePhenytoin 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).
MetyrosineCNS Depressants may enhance the sedative effect of Metyrosine.
MexiletinePhenytoin may decrease the serum concentration of Mexiletine.
MianserinMay diminish the therapeutic effect of Phenytoin. Phenytoin may decrease the serum concentration of Mianserin.
MiconazoleMiconazole (Oral) may increase the serum concentration of Phenytoin.
MifepristoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Mifepristone.
NabiloneMay enhance the CNS depressant effect of CNS Depressants.
NelfinavirNelfinavir may decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Nelfinavir.
NicardipineMay increase the serum concentration of Phenytoin.
NifedipineCYP3A4 Inducers (Strong) may decrease the serum concentration of NIFEdipine.
NilotinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Nilotinib.
NimodipineMay increase the serum concentration of Phenytoin.
NisoldipineMay increase the serum concentration of Phenytoin.
NitrazepamBenzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
NitrendipineMay increase the serum concentration of Phenytoin.
Nitric OxideMay enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
NorelgestrominMay diminish the therapeutic effect of Contraceptives (Estrogens). Contraceptive failure is possible.
NorethindroneMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
NorgestimateMay diminish the therapeutic effect of Contraceptives (Progestins). Contraceptive failure is possible.
OmeprazoleMay increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Omeprazole.
OrlistatMay decrease the serum concentration of Anticonvulsants.
OrphenadrineCNS Depressants may enhance the CNS depressant effect of Orphenadrine.
OxazepamBenzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
OxcarbazepineFosphenytoin-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.
PaliperidoneInducers of CYP3A4 and P-glycoprotein may decrease the serum concentration of Paliperidone.
PanobinostatCYP3A4 Inducers (Strong) may decrease the serum concentration of Panobinostat.
PazopanibCYP3A4 Inducers (Strong) may decrease the serum concentration of PAZOPanib.
PerampanelPhenytoin may decrease the serum concentration of Perampanel.
PerhexilineMay increase the serum concentration of Phenytoin.
PethidineMay decrease the serum concentration of Meperidine.
PhendimetrazineAmphetamines may decrease the serum concentration of Phenytoin.
PhenobarbitalPhenytoin may enhance the CNS depressant effect of PHENobarbital. PHENobarbital may decrease the serum concentration of Phenytoin. Phenytoin may increase the serum concentration of PHENobarbital.
PhentermineAmphetamines may decrease the serum concentration of Phenytoin.
PonatinibCYP3A4 Inducers (Strong) may decrease the serum concentration of PONATinib.
PosaconazoleMay decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs.
PramipexoleCNS Depressants may enhance the sedative effect of Pramipexole.
PravastatinMay decrease the serum concentration of HMG-CoA Reductase Inhibitors.
PraziquantelCYP3A4 Inducers (Strong) may decrease the serum concentration of Praziquantel.
PrednisoneCYP3A4 Inducers (Strong) may decrease the serum concentration of PredniSONE.
PrenylamineMay increase the serum concentration of Phenytoin.
PrilocaineMethemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia.
PrimidonePhenytoin may increase the metabolism of Primidone. The ratio of primidone:phenobarbital is thus changed.
PyridoxinePyridoxine may increase the metabolism of Phenytoin. This is most apparent in high pyridoxine doses (e.g., 80 mg to 200 mg daily)
QuazepamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
QuetiapineCYP3A4 Inducers (Strong) may decrease the serum concentration of QUEtiapine.
QuinidinePhenytoin may decrease the serum concentration of QuiNIDine.
QuininePhenytoin may decrease the serum concentration of QuiNINE.
RanolazineCYP3A4 Inducers (Strong) may decrease the serum concentration of Ranolazine.
RegorafenibCYP3A4 Inducers (Strong) may decrease the serum concentration of Regorafenib.
RifampicinRifampin may decrease the serum concentration of Phenytoin.
RilpivirinePhenytoin may decrease the serum concentration of Rilpivirine.
RisedronateMay increase the serum concentration of Phenytoin.
RitonavirPhenytoin may decrease the serum concentration of Ritonavir. Ritonavir may decrease the serum concentration of Phenytoin.
RivaroxabanCYP3A4 Inducers (Strong) may decrease the serum concentration of Rivaroxaban.
RoflumilastCYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast.
RomidepsinCYP3A4 Inducers (Strong) may decrease the serum concentration of RomiDEPsin.
RopiniroleCNS Depressants may enhance the sedative effect of ROPINIRole.
RotigotineCNS Depressants may enhance the sedative effect of Rotigotine.
RufinamidePhenytoin may decrease the serum concentration of Rufinamide. Rufinamide may increase the serum concentration of Phenytoin.
SaxagliptinCYP3A4 Inducers may decrease the serum concentration of Saxagliptin.
SertralinePhenytoin may decrease the serum concentration of Sertraline. Sertraline may increase the serum concentration of Phenytoin.
SimeprevirCYP3A4 Inducers (Strong) may decrease the serum concentration of Simeprevir.
SimvastatinMay decrease the serum concentration of HMG-CoA Reductase Inhibitors.
SirolimusPhenytoin may decrease the serum concentration of Sirolimus.
SofosbuvirP-glycoprotein/ABCB1 Inducers may decrease the serum concentration of Sofosbuvir.
SorafenibCYP3A4 Inducers (Strong) may decrease the serum concentration of SORAfenib.
SulfamethoxazoleMay increase the serum concentration of Phenytoin.
SunitinibCYP3A4 Inducers (Strong) may decrease the serum concentration of SUNItinib.
SuvorexantCYP3A4 Inducers (Strong) may decrease the serum concentration of Suvorexant.
TadalafilCYP3A4 Inducers (Strong) may decrease the serum concentration of Tadalafil.
TapentadolMay enhance the CNS depressant effect of CNS Depressants.
TelaprevirPhenytoin may decrease the serum concentration of Telaprevir. Telaprevir may increase the serum concentration of Phenytoin.
TemazepamBenzodiazepines may increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy.
TemsirolimusPhenytoin 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).
TeniposidePhenytoin may decrease the serum concentration of Teniposide.
ThalidomideCNS Depressants may enhance the CNS depressant effect of Thalidomide.
TheophyllineTheophylline Derivatives may decrease the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Theophylline Derivatives.
TicagrelorCYP3A4 Inducers (Strong) may decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor.
TiclopidineTiclopidine may increase the serum concentration of Phenytoin.
TipranavirPhenytoin may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Phenytoin.
TofacitinibCYP3A4 Inducers (Strong) may decrease the serum concentration of Tofacitinib.
TofisopamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
TolvaptanCYP3A4 Inducers (Strong) may decrease the serum concentration of Tolvaptan.
TopiramatePhenytoin may decrease the serum concentration of Topiramate. Topiramate may increase the serum concentration of Phenytoin.
TopotecanFosphenytoin-Phenytoin may decrease the serum concentration of Topotecan.
ToremifeneCYP3A4 Inducers (Strong) may decrease the serum concentration of Toremifene.
TrabectedinCYP3A4 Inducers (Strong) may decrease the serum concentration of Trabectedin.
TrazodonePhenytoin may decrease the serum concentration of TraZODone. TraZODone may increase the serum concentration of Phenytoin.
TreprostinilCYP2C8 Inducers (Strong) may decrease the serum concentration of Treprostinil.
TriazolamMay increase the serum concentration of Phenytoin. Short-term exposure to benzodiazepines may not present as much risk as chronic therapy. Exceptions: ALPRAZolam.
TrimethoprimPhenytoin may decrease the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Phenytoin.
UlipristalCYP3A4 Inducers (Strong) may decrease the serum concentration of Ulipristal.
VandetanibCYP3A4 Inducers (Strong) may decrease the serum concentration of Vandetanib.
VemurafenibCYP3A4 Inducers (Strong) may decrease the serum concentration of Vemurafenib.
VerapamilMay increase the serum concentration of Phenytoin.
VigabatrinMay decrease the serum concentration of Phenytoin.
VilazodoneCYP3A4 Inducers (Strong) may decrease the serum concentration of Vilazodone.
VincristinePhenytoin may decrease the serum concentration of VinCRIStine. VinCRIStine may decrease the serum concentration of Phenytoin.
VorapaxarCYP3A4 Inducers (Strong) may decrease the serum concentration of Vorapaxar.
VoriconazoleMay decrease the serum concentration of Antifungal Agents (Azole Derivatives, Systemic). Antifungal Agents (Azole Derivatives, Systemic) may increase the serum concentration of Phenytoin. Applicable Isavuconazonium considerations are addressed in separate monographs.
ZolpidemCNS Depressants may enhance the CNS depressant effect of Zolpidem.
ZonisamidePhenytoin may decrease the serum concentration of Zonisamide.
ZuclopenthixolCYP3A4 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.

Targets

1. Sodium channel protein type 5 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 5 subunit alpha Q14524 Details

References:

  1. Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. Pubmed
  2. Swadron SP, Rudis MI, Azimian K, Beringer P, Fort D, Orlinsky M: A comparison of phenytoin-loading techniques in the emergency department. Acad Emerg Med. 2004 Mar;11(3):244-52. Pubmed

2. Sodium channel protein type 1 subunit alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Sodium channel protein type 1 subunit alpha P35498 Details

References:

  1. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. Pubmed
  2. Tate SK, Singh R, Hung CC, Tai JJ, Depondt C, Cavalleri GL, Sisodiya SM, Goldstein DB, Liou HH: A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-726. Pubmed
  3. Mantegazza M, Curia G, Biagini G, Ragsdale DS, Avoli M: Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders. Lancet Neurol. 2010 Apr;9(4):413-24. Pubmed

Enzymes

1. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. Pubmed
  5. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  6. Komatsu T, Yamazaki H, Asahi S, Gillam EM, Guengerich FP, Nakajima M, Yokoi T: Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab Dispos. 2000 Nov;28(11):1361-8. Pubmed
  7. Lexicomp

2. Cytochrome P450 2C19

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

References:

  1. Levy RH: Cytochrome P450 isozymes and antiepileptic drug interactions. Epilepsia. 1995;36 Suppl 5:S8-13. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. Komatsu T, Yamazaki H, Asahi S, Gillam EM, Guengerich FP, Nakajima M, Yokoi T: Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab Dispos. 2000 Nov;28(11):1361-8. Pubmed
  6. Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. Pubmed
  7. Lexicomp

3. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  3. Lexicomp

4. Cytochrome P450 2B6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

References:

  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Lexicomp

5. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Lexicomp

6. Cytochrome P450 2C18

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 2C18 P33260 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

7. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 3A7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

9. Cytochrome P450 11B1, mitochondrial

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 11B1, mitochondrial P15538 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Chen J, Ohnmacht C, Hage DS: Studies of phenytoin binding to human serum albumin by high-performance affinity chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Sep 25;809(1):137-45. Pubmed
  2. Ohnmacht CM, Chen S, Tong Z, Hage DS: Studies by biointeraction chromatography of binding by phenytoin metabolites to human serum albumin. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 May 19;836(1-2):83-91. Epub 2006 Apr 18. Pubmed

Transporters

1. Solute carrier organic anion transporter family member 1C1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1C1 Q9NYB5 Details

References:

  1. Westholm DE, Stenehjem DD, Rumbley JN, Drewes LR, Anderson GW: Competitive inhibition of organic anion transporting polypeptide 1c1-mediated thyroxine transport by the fenamate class of nonsteroidal antiinflammatory drugs. Endocrinology. 2009 Feb;150(2):1025-32. Epub 2008 Oct 9. Pubmed
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

2. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed
  2. Luna-Tortos C, Fedrowitz M, Loscher W: Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75. Epub 2008 Sep 11. Pubmed

3. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Baltes S, Gastens AM, Fedrowitz M, Potschka H, Kaever V, Loscher W: Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46. Epub 2006 Oct 10. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08