Drug/Small Molecule:
phenytoin

Available Guidelines

  1. CPIC Dosing Guideline for phenytoin and CYP2C9, HLA-B
  2. Dutch Pharmacogenetics Working Group Guideline for phenytoin and CYP2C9

last updated 08/05/2014

CPIC Dosing Guideline for phenytoin and CYP2C9, HLA-B

Annotation

August 2014

Accepted article preview online August 2014

  • Guidelines regarding the use of pharmacogenomic tests in dosing for phenytoin have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • Excerpt from the 2014 phenytoin dosing guidelines:
    • "[A]t least a 25% reduction of the recommended starting maintenance dose may be considered for CYP2C9 intermediate metabolizers with subsequent maintenance doses adjusted based on therapeutic drug monitoring and response. For CYP2C9 poor metabolizers, consider at least a 50% reduction of starting maintenance dose with subsequent maintenance doses adjusted based on therapeutic drug monitoring or response."
    • "[R]egardless of the CYP2C9 genotype and individual's ancestry or age, if the HLA-B*15:02 test result is positive, the recommendation is to consider using an anticonvulsant other than carbamazepine and phenytoin unless the benefits of treating the underlying disease clearly outweigh the risks... Alternative medications such as oxcarbazepine, eslicarbazepine acetate, and lamotrigine have some evidence linking SJS/TEN with the HLA-B*15:02 allele and thus caution should be used in choosing alternatives to phenytoin."
  • Download and read:

Table 1: Phenytoin/fosphenytoin therapy recommendations based on HLA-B and CYP2C9 phenotype/genotype

Adapted from Tables 1 and 2 of the 2014 guideline manuscript.

Phenotype/Genotype HLA-B*15:02 carrier
1 or 2 *15:02 alleles; "positive"
HLA-B*15:02 non-carrier
No HLA-B*15:02 alleles reported; "negative"
CYP2C9 Extensive Metabolizer
normal activity ~91% of patients
*1/*1
Increased risk of phenytoin-induced SJS/TEN.
If patient is phenytoin-naive b, do not use phenytoin/fosphenytoin.
STRONG
Normal phenytoin metabolism.
Initiate therapy with recommended maintenance dose d.
STRONG
CYP2C9 Intermediate Metabolizer
heterozygote ~8% of patients
*1/*3, *1/*2
Increased risk of phenytoin-induced SJS/TEN.
If patient is phenytoin-naive b, do not use phenytoin/fosphenytoin.
STRONG
Reduced phenytoin metabolism, higher plasma concentrations will increase probability of toxicities.
Consider 25% reduction of recommended starting maintenance dose d. Subsequent doses should be adjusted according to therapeutic drug monitoring and response.
MODERATE
CYP2C9 Poor Metabolizer
homozygous variant ~1% of patients
*2/*2, *3/*3, *2/*3
Increased risk of phenytoin-induced SJS/TEN.
If patient is phenytoin-naive b, do not use phenytoin/fosphenytoin.
STRONG
Reduced phenytoin metabolism, higher plasma concentrations will increase probability of toxicities.
Consider 50% reduction of recommended starting maintenance dose d. Subsequent maintenance doses should be adjusted according to therapeutic drug monitoring and response.
STRONG

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for phenytoin and CYP2C9

Summary

Use the standard starting dose of phenytoin and reduce the maintenance dose based on CYP2C9 genotype; monitor response and serum concentrations and be aware of ADEs.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for phenytoin based on CYP2C9 genotype (PMID:21412232).

Genotype Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
CYP2C9 *1/*2 Standard loading dose. Reduce maintenance dose by 25%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation) Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 *2/*2 Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation) Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 *1/*3 Standard loading dose. Reduce maintenance dose by 25%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation) Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10{^}9^/l; leucopenia 1.0-2.0x10{^}9^/l; thrombocytopenia 25-50x10{^}9^/l; severe diarrhea
CYP2C9 *2/*3 Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation) Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Minor clinical effect (S): QTc prolongation (<450 ms females, <470 ms males); INR increase < 4.5Kinetic effect (S)
CYP2C9 *3/*3 Standard loading dose. Reduce maintenance dose by 50%. Evaluate response and serum concentration after 7-10 days. Be alert to ADEs (e.g., ataxia, nystagmus, dysarthria, sedation) Published controlled studies of good quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): long-standing discomfort (> 168 hr), permanent symptom or invalidating injury e.g. failure of prophylaxis of atrial fibrillation; venous thromboembolism; decreased effect of clopidogrel on inhibition of platelet aggregation; ADE resulting from increased bioavailability of phenytoin; INR > 6.0; neutropenia 0.5-1.0x10{^}9^/l; leucopenia 1.0-2.0x10{^}9^/l; thrombocytopenia 25-50x10{^}9^/l; severe diarrhea

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.


last updated 10/25/2013

FDA Label for phenytoin and HLA-B

This label is on the FDA Biomarker List
Actionable PGx

Summary

A strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine. Limited evidence suggests that HLAB*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.

Annotation

Phenytoin sodium is an antiepileptic drug.

Excerpt from the phenytoin sodium (Dilantin) drug label:

There may be wide interpatient variability in phenytoin serum levels with equivalent dosages. Patients with unusually low levels may be noncompliant or hypermetabolizers of phenytoin. Unusually high levels result from liver disease, variant CYP2C9 and CYP2C19 alleles, or drug interactions which result
in metabolic interference.

Phenytoin is metabolized by hepatic cytochrome P450 enzymes CYP2C9 and CYP2C19, and is particularly susceptible to inhibitory drug interactions because it is subject to saturable metabolism. Inhibition of metabolism may produce significant increases in circulating phenytoin concentrations and enhance the risk of drug toxicity. Phenytoin is a potent inducer of hepatic drug-metabolizing enzymes. Serum level determinations for phenytoin are especially helpful when possible drug interactions are suspected.

Studies in patients of Chinese ancestry have found a strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine. Limited evidence suggests that HLAB*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Phenytoin sodium (Dilantin) drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Congenital Abnormalities
    • Warnings section
    • source: PHONT
  • Epidermal Necrolysis, Toxic
    • Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Epilepsy
    • Warnings section, Adverse reactions section, Precautions section, Mechanism of action section
    • source: PHONT
  • Hypersensitivity
    • Contraindications section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Leukemia
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Seizures
    • Indications & usage section, Warnings section, Adverse reactions section, Precautions section
    • source: PHONT
  • Stevens-Johnson Syndrome
    • Adverse reactions section
    • source: PHONT
  • CYP2C19
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • CYP2C9
    • Drug interactions section, Pharmacokinetics section, metabolism/PK
    • source: FDA Label
  • HLA-B
    • Warnings section, toxicity
    • source: FDA Label

Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
Roche AmpliChip CYP450 Test Variant in CYP2C19
HLA-B*1502 Carbamazepine Sensitivity rs3909184 , rs2844682 , HLA-B*1502
Spartan RX CYP2C19 System CYP2C19*17, CYP2C19*2, CYP2C19*3 , rs12248560 , rs4986893 , rs4244285

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
VIP No VIP available No VIP available CYP2C19 *2A N/A N/A N/A
VIP No VIP available No VIP available CYP2C19 *3A N/A N/A N/A
No VIP available CA VA CYP2C9 *1 N/A N/A N/A
VIP CA VA CYP2C9 *2 N/A N/A N/A
VIP CA VA CYP2C9 *3 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2D6 *41 N/A N/A N/A
No VIP available No VIP available VA HLA-A *03:01:01:01 N/A N/A N/A
No VIP available CA VA HLA-B *13:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *15:01:01:01 N/A N/A N/A
VIP CA VA HLA-B *15:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *37:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *46:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *51:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *51:02:01 N/A N/A N/A
No VIP available No VIP available VA HLA-B *54:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-C *08:01:01 N/A N/A N/A
No VIP available No VIP available VA HLA-DRB1 *16:02:01 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs10068980 161287847G>A, 18651G>A, 188-4880G>A, 6099120G>A
G > A
Intronic
No VIP available CA VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available CA VA
rs1051740 19537412T>C, 226019633T>C, 26837T>C, 337T>C, EPHX1: Y113H, NM_000120.2: c.337T>C, NT_004559.13: g.2221786T>C, Tyr113His, c.337T>C, mRNA 378T>C, mRNA 612T>C, p.Tyr113His
T > C
Missense
Tyr113His
rs1057910 1075A>C, 47545517A>C, 47639A>C, 96741053A>C, CYP2C9*3, CYP2C9*3:Ile359Leu, CYP2C9: I359L, CYP2C9:359Ile>Leu, CYP2C9:Ile359Leu, Ile359Leu, mRNA 11A>C
A > C
Missense
Ile359Leu
No VIP available No Clinical Annotations available VA
rs1112122 -27+13614C>A, 151606004G>T, 18827C>A, 2523942G>T
G > T
Intronic
No VIP available CA VA
rs1128503 1236T>C, 167964T>C, 25043506A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Not Available
Gly412Gly
No VIP available No Clinical Annotations available VA
rs1157122 161319314T>C, 50118T>C, 6130587T>C, 856+1258T>C
T > C
Intronic
No VIP available CA VA
rs12782374 1937G>A, 47499815G>A, 96695351G>A
G > A
Not Available
No VIP available CA VA
rs17183814 16361807G>A, 166152389G>A, 56G>A, 61478G>A, Arg19Lys
G > A
Missense
Arg19Lys
rs1799853 430C>T, 47506511C>T, 8633C>T, 96702047C>T, Arg144Cys, CYP2C9*2, CYP2C9:144Arg>Cys, CYP2C9:Arg144Cys, mRNA 455C>T
C > T
Missense
Arg144Cys
No VIP available No Clinical Annotations available VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > C
A > T
Missense
Ser893Ala
Ser893Thr
No VIP available No Clinical Annotations available VA
rs211037 161528280C>T, 38633C>T, 588C>T, 6339553C>T, Asn196=
C > T
Synonymous
Asn196Asn
No VIP available No Clinical Annotations available VA
rs2229107 208906T>A, 25171502A>T, 3421T>A, 87138659A>T, ABCB: S1141T, Ser1141Thr
A > T
Missense
Ser1141Thr
No VIP available No Clinical Annotations available VA
rs2229944 1194C>T, 1308C>T, 160721319G>A, 5532592G>A, Ala398=, Ala436=
G > A
Synonymous
Ala436Ala
No VIP available CA VA
rs2234922 19544185A>G, 226026406A>G, 33610A>G, 416A>G, EPHX1: H139R, His139Arg, NM_000120.2: c.416A>G, NT_004559.13: g.2228559A>G, mRNA 457A>G, mRNA 691A>G, p.His139Arg
A > G
Missense
His139Arg
No VIP available CA VA
rs2279020 1059+15G>A, 161322889G>A, 53693G>A, 6134162G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs2298771
C > T
Not Available
Ala1056Thr
No VIP available CA VA
rs2304016 16377921A>G, 166168503A>G, 77592A>G, 971-32A>G, SCN2A:IVS7-32A>G
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2606345 -27+606G>T, 45807733C>A, 7294C>A, 75017176C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs28371685 1003C>T, 47545445C>T, 47567C>T, 96740981C>T, Arg335Trp, CYP2C9*11, CYP2C9:R335W
C > T
Missense
Arg335Trp
No VIP available No Clinical Annotations available VA
rs28371686 1080C>G, 47545522C>G, 47644C>G, 96741058C>G, Asp360Glu, CYP2C9*5, CYP2C9:D360E
C > G
Missense
Asp360Glu
No VIP available No Clinical Annotations available VA
rs28399504 1A>G, 47326927A>G, 5001A>G, 80161A>G, 96522463A>G, 99C>T, CYP2C19*4, CYP2C19:A1G, Met1Val
A > G
Missense
Met1Val
No VIP available No Clinical Annotations available VA
rs3219151 *135C>T, 161128914C>T, 5940187C>T
C > T
3' UTR
No VIP available CA VA
rs3812718 166909544C>T, 17118962C>T, 25606G>A, 603-91G>A
C > T
Intronic
rs4244285 24154G>A, 24154G>C, 47346080G>A, 47346080G>C, 681G>A, 681G>C, 96541616G>A, 96541616G>C, CYP2C19*2, CYP2C19:681G>A, CYP2C19:G681A, Pro227=
G > C
G > A
Synonymous
Pro227Pro
No VIP available No Clinical Annotations available VA
rs4828696 -27+37622A>G, 151581996T>C, 2499934T>C, 42835A>G
T > C
Intronic
rs4986893 22948G>A, 47344874G>A, 636G>A, 96540410G>A, CYP2C19*3, CYP2C19:636G>A, CYP2C19:G636A, Trp212Ter
G > A
Stop Codon
Trp212null
No VIP available No Clinical Annotations available VA
rs511310 46240004A>G, 5942908A>G
A > G
Not Available
No VIP available No Clinical Annotations available VA
rs6883877 161278338C>T, 6089611C>T, 74+448C>T, 9142C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs6892782 161269783T>C, 587T>C, 6081056T>C
T > C
Not Available
No VIP available CA VA
rs71486745 2362_2363delGT, 47500240_47500241delGT, 96695776_96695777delGT
GT > -
Not Available
No VIP available No Clinical Annotations available VA
rs7900194 449G>A, 449G>T, 47506530G>A, 47506530G>T, 8652G>A, 8652G>T, 96702066G>A, 96702066G>T, Arg150His, Arg150Leu, CYP2C9*8, CYP2C9:R150H
G > T
G > A
Missense
Arg150Leu
Arg150His
No VIP available CA VA
rs9332131 15625delA, 47513503delA, 817delA, 96709039delA, CYP2C9*6, CYP2C9:null allele, Lys273Argfs
A > -
Frameshift
Lys273Arg
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 5,5-Dwufenylohydantoina
  • 5,5-diphenylhydantoin
  • DPH
  • Difenilhidantoina [Spanish]
  • Dihydantoin
  • Diphenylan Sodium
  • Diphenylhydantoin
  • Diphenylhydantoine [French]
  • Diphenylhydatanoin
  • Fenitoina [INN-Spanish]
  • Phenytoin Sodium
  • Phenytoine
  • Phenytoine [INN-French]
  • Phenytoinum [INN-Latin]
Trade Names
  • Aleviatin
  • Antisacer
  • Auranile
  • Causoin
  • Citrullamon
  • Citrulliamon
  • Comital
  • Comitoina
  • Convul
  • Danten
  • Dantinal
  • Dantoinal
  • Dantoinal klinos
  • Dantoine
  • Denyl
  • Di-Hydan
  • Di-Lan
  • Di-Phetine
  • Didan TDC 250
  • Difenilhidantoina
  • Difenin
  • Difetoin
  • Difhydan
  • Dihycon
  • Dilabid
  • Dilantin
  • Dilantin acid
  • Dilantin-125
  • Dilantine
  • Dillantin
  • Dintoin
  • Dintoina
  • Diphantoin
  • Diphedal
  • Diphedan
  • Diphenat
  • Diphenin
  • Diphenine
  • Diphentoin
  • Diphentyn
  • Diphenylan
  • Ditoinate
  • Ekko
  • Elepsindon
  • Enkelfel
  • Epamin
  • Epanutin
  • Epasmir 5
  • Epdantoin Simple
  • Epdantoine simple
  • Epelin
  • Epifenyl
  • Epihydan
  • Epilan
  • Epilan D
  • Epilan-D
  • Epilantin
  • Epinat
  • Epised
  • Eptal
  • Eptoin
  • Fenantoin
  • Fenidantoin s
  • Fentoin
  • Fenylepsin
  • Fenytoin Dak
  • Fenytoine
  • Gerot-epilan-D
  • Hidan
  • Hidantal
  • Hidantilo
  • Hidantina
  • Hidantina senosian
  • Hidantina vitoria
  • Hidantomin
  • Hindatal
  • Hydantal
  • Hydantin
  • Hydantoin
  • Hydantoinal
  • Hydantol
  • Ictalis simple
  • Idantoil
  • Idantoin
  • Iphenylhydantoin
  • Kessodanten
  • Labopal
  • Lehydan
  • Lepitoin
  • Lepsin
  • Mesantoin
  • Minetoin
  • Neos-Hidantoina
  • Neosidantoina
  • Novantoina
  • Novophenytoin
  • Om hidantoina simple
  • Om-Hydantoine
  • Oxylan
  • Phanantin
  • Phanatine
  • Phenatine
  • Phenatoine
  • Phenhydan
  • Phenhydanin
  • Phenitoin
  • Phentoin
  • Phentytoin
  • Phenytex
  • Phenytoin AWD
  • Phenytoin-Gerot
  • Prompt Phenytoin Sodium
  • Ritmenal
  • Saceril
  • Sanepil
  • Silantin
  • Sinergina
  • Sodanthon
  • Sodantoin
  • Sodanton
  • Solantin
  • Solantoin
  • Solantyl
  • Sylantoic
  • TOIN
  • Tacosal
  • Thilophenyl
  • Toin unicelles
  • Zentronal
  • Zentropil
Brand Mixture Names
  • Dilantin W Phenobarbital 15mg (Phenobarbital + Phenytoin Sodium)
  • Dilantin W Phenobarbital 30mg Cap (Phenobarbital + Phenytoin Sodium)

PharmGKB Accession Id:
PA450947

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.

Source: Drug Bank

Indication

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.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Food Interaction

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

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Primarily hepatic

Source: Drug Bank

Protein Binding

Highly protein bound, 90%

Source: Drug Bank

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.

Source: Drug Bank

Half-Life

22 hours (range of 7 to 42 hours)

Source: Drug Bank

Toxicity

Oral, mouse: LD 50 = 150 mg/kg; Oral, rat: LD 50 = 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.

Source: Drug Bank

Route of Elimination

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.

Source: Drug Bank

Chemical Properties

Chemical Formula

C15H12N2O2

Source: Drug Bank

Isomeric SMILES

c1ccc(cc1)C2(C(=O)NC(=O)N2)c3ccccc3

Source: OpenEye

Canonical SMILES

O=C1NC(=O)C(N1)(C1=CC=CC=C1)C1=CC=CC=C1

Source: Drug Bank

Average Molecular Weight

252.268

Source: Drug Bank

Monoisotopic Molecular Weight

252.089877638

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Phenytoin Pathway, Pharmacokinetics
    Genes involved in the metabolism of phenytoin in the human liver cell.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
SCN1A (source: Drug Bank)
SCN5A (source: Drug Bank)

Curated Information ?

EvidenceDrug
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
acetaminophen

Drug Interactions

Drug Description
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Decreased effect of both products (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin The CYP3A4 inducer, phenytoin, may decrease the effect of aprepitant. (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, betamethasone. (source: Drug Bank)
phenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
phenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases phenytoin, modifies chloramphenicol (source: Drug Bank)
phenytoin Increases phenytoin, modifies chloramphenicol (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The antihistamine increases the effect of hydantoin (source: Drug Bank)
phenytoin The antihistamine increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Decreases the hydantoin effect (source: Drug Bank)
phenytoin Decreases the hydantoin effect (source: Drug Bank)
phenytoin Increases the effect and toxicity of phenytoin (source: Drug Bank)
phenytoin Increases the effect and toxicity of phenytoin (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of hormones (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, clomifene. (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
phenytoin Hydantoin decreases the effect of clozapine (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, conjugated estrogens. (source: Drug Bank)
phenytoin The hydantoin decreases the effect of cyclosporine (source: Drug Bank)
phenytoin The hydantoin decreases the effect of cyclosporine (source: Drug Bank)
phenytoin The anticonvulsant decreases the effect of delavirdine (source: Drug Bank)
phenytoin The anticonvulsant, phenytoin, decreases the effect of delavirdine. (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, dexamethasone. (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of hormones (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, diethylstilbestrol. (source: Drug Bank)
phenytoin The hydantoin decreases the effect of disopyramide (source: Drug Bank)
phenytoin The hydantoin decreases the effect of disopyramide (source: Drug Bank)
phenytoin Increases the effect of phenytoin (source: Drug Bank)
phenytoin Increases the effect of phenytoin (source: Drug Bank)
phenytoin Valproate increases the effect of hydantoin (source: Drug Bank)
phenytoin The anticonvulsant decreases the effect of doxycycline (source: Drug Bank)
phenytoin The anticonvulsant, phenytoin, decreases the effect of doxycycline. (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of hormones (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estradiol. (source: Drug Bank)
phenytoin This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
phenytoin This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
phenytoin Increased phenytoin levels and decreased felbamate levels (source: Drug Bank)
phenytoin Increased phenytoin levels and decreased felbamate levels (source: Drug Bank)
phenytoin The hydantoin decreases the effect of felodipine (source: Drug Bank)
phenytoin The hydantoin decreases the effect of felodipine (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, fludrocortisone. (source: Drug Bank)
phenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
phenytoin Fluorouracil increases the effect of hydantoin (source: Drug Bank)
phenytoin Fluoxetine increases the effect of phenytoin (source: Drug Bank)
phenytoin Fluoxetine increases the effect of phenytoin (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Folic acid decreases the levels of hydantoin (source: Drug Bank)
phenytoin Folic acid decreases the levels of hydantoin (source: Drug Bank)
phenytoin The hydantoin decreases the effect of furosemide (source: Drug Bank)
phenytoin The hydantoin decreases the effect of furosemide (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin Increases the effect of hydantoin (source: Drug Bank)
phenytoin This CYP3A4 inducer may reduce gefitinib concentrations and pharmacological effects (source: Drug Bank)
phenytoin The CYP3A4 inducer, phenytoin, may decrease the serum concentration and therapeutic effects of gefitinib. (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, hydrocortisone. (source: Drug Bank)
phenytoin The hydantoin decreases the levels of imatinib (source: Drug Bank)
phenytoin The hydantoin decreases the levels of imatinib (source: Drug Bank)
phenytoin Isoniazid increases the effect of phenytoin in 20% of patients (source: Drug Bank)
phenytoin Isoniazid increases the effect of phenytoin in 20% of patients (source: Drug Bank)
phenytoin Phenytoin decreases the effect of itraconazole (source: Drug Bank)
phenytoin Phenytoin decreases the effect of itraconazole (source: Drug Bank)
phenytoin Phenytoin may reduce levels of lamotrigine (source: Drug Bank)
phenytoin Phenytoin may reduce levels of lamotrigine (source: Drug Bank)
phenytoin Phenytoin decreases the contraceptive effect (source: Drug Bank)
phenytoin Phenytoin decreases the contraceptive effect (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The hydantoin decreases the efficiency of mebendazole (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of hormones (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, medroxyprogesterone. (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of hormones (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, decreases the effect of the hormone agent, megestrol. (source: Drug Bank)
phenytoin The hydantoin decreases the effect of methadone (source: Drug Bank)
phenytoin The hydantoin decreases the effect of methadone (source: Drug Bank)
phenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
phenytoin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
phenytoin The hydantoin decreases the effect of psoralene (source: Drug Bank)
phenytoin The hydantoin decreases the effect of psoralene (source: Drug Bank)
phenytoin The hydantoin decreases the effect of mexiletine (source: Drug Bank)
phenytoin The hydantoin decreases the effect of mexiletine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
phenytoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
phenytoin This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
phenytoin This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
phenytoin Omeprazole increases the effect of hydantoin (source: Drug Bank)
phenytoin Omeprazole increases the effect of hydantoin (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Oxcarbazepine increases the effect of hydantoin (source: Drug Bank)
phenytoin Oxcarbazepine increases the effect of hydantoin (source: Drug Bank)
phenytoin Decreased effect of both products (source: Drug Bank)
phenytoin The NSAID increases the hydantoin effect (source: Drug Bank)
phenytoin The NSAID, oxyphenbutazone, may increase the hydantoin effect of phenytoin. (source: Drug Bank)
phenytoin The NSAID increases the hydantoin effect (source: Drug Bank)
phenytoin The NSAID, phenylbutazone, may increase the hydantoin effect of phenytoin. (source: Drug Bank)
acenocoumarol Increased hydantoin levels and risk of bleeding (source: Drug Bank)
acenocoumarol Increased hydantoin levels and risk of bleeding (source: Drug Bank)
alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
alprazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
aminophylline Decreased effect of both products (source: Drug Bank)
aminophylline Decreased effect of both products (source: Drug Bank)
amiodarone Amiodarone increases the effect of hydantoin (source: Drug Bank)
amiodarone Amiodarone increases the effect of hydantoin (source: Drug Bank)
anisindione Increased hydantoin levels and risk of bleeding (source: Drug Bank)
anisindione Increased hydantoin levels and risk of bleeding (source: Drug Bank)
aprepitant This CYP3A4 inducer decreases the effect of aprepitant (source: Drug Bank)
aprepitant The CYP3A4 inducer, phenytoin, may decrease the effect of aprepitant. (source: Drug Bank)
atracurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
atracurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
betamethasone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
betamethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, betamethasone. (source: Drug Bank)
bleomycin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
bleomycin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
capecitabine Capecitabine increases the effect of hydantoin (source: Drug Bank)
capecitabine Capecitabine increases the effect of hydantoin (source: Drug Bank)
carboplatin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
carboplatin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
carmustine The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
carmustine The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
chloramphenicol Increases phenytoin, modifies chloramphenicol (source: Drug Bank)
chloramphenicol Increases phenytoin, modifies chloramphenicol (source: Drug Bank)
chlordiazepoxide Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
chlordiazepoxide Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
chlorotrianisene The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
chlorotrianisene The enzyme inducer, phenytoin, decreases the effect of the hormone agent, chlorotrianisene. (source: Drug Bank)
chlorpheniramine The antihistamine increases the effect of hydantoin (source: Drug Bank)
chlorpheniramine The antihistamine increases the effect of hydantoin (source: Drug Bank)
cimetidine Cimetidine increases the effect of hydantoin (source: Drug Bank)
cimetidine Cimetidine increases the effect of hydantoin (source: Drug Bank)
ciprofloxacin Ciprofloxacin decreases the hydantoin effect (source: Drug Bank)
ciprofloxacin Ciprofloxacin decreases the hydantoin effect (source: Drug Bank)
cisplatin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
cisplatin The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
clarithromycin Clarithromycin increases the effect and toxicity of phenytoin (source: Drug Bank)
clarithromycin Clarithromycin increases the effect and toxicity of phenytoin (source: Drug Bank)
clomifene The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
clomifene The enzyme inducer, phenytoin, decreases the effect of the hormone agent, clomifene. (source: Drug Bank)
clorazepate Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
clorazepate Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
clozapine The hydantoin decreases the effect of clozapine (source: Drug Bank)
clozapine The hydantoin decreases the effect of clozapine (source: Drug Bank)
conjugated estrogens The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
conjugated estrogens The enzyme inducer, phenytoin, decreases the effect of the hormone agent, conjugated estrogens. (source: Drug Bank)
cortisone acetate The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
cyclosporine The hydantoin decreases the effect of cyclosporine (source: Drug Bank)
cyclosporine The hydantoin decreases the effect of cyclosporine (source: Drug Bank)
dasatinib Decreased levels/efficacy of dasatinib (source: Drug Bank)
dasatinib Phenytoin may decrease the serum level and efficacy of dasatinib. (source: Drug Bank)
delavirdine The anticonvulsant decreases the effect of delavirdine (source: Drug Bank)
delavirdine The anticonvulsant, phenytoin, decreases the effect of delavirdine. (source: Drug Bank)
dexamethasone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
dexamethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, dexamethasone. (source: Drug Bank)
diazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
diazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
diazoxide Diazoxide decreases the hydantoin effect (source: Drug Bank)
diazoxide Diazoxide decreases the efficacy of phenytoin. (source: Drug Bank)
dicumarol Increased hydantoin levels and risk of bleeding (source: Drug Bank)
dicumarol Increased hydantoin levels and risk of bleeding (source: Drug Bank)
diethylstilbestrol The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
diethylstilbestrol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, diethylstilbestrol. (source: Drug Bank)
disopyramide The hydantoin decreases the effect of disopyramide (source: Drug Bank)
disopyramide The hydantoin decreases the effect of disopyramide (source: Drug Bank)
disulfiram Disulfiram increases the effect of phenytoin (source: Drug Bank)
disulfiram Disulfiram increases the effect of phenytoin (source: Drug Bank)
dopamine Risk of severe hypotension (source: Drug Bank)
dopamine Risk of severe hypotension (source: Drug Bank)
doxacurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
doxacurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
doxycycline The anticonvulsant decreases the effect of doxycycline (source: Drug Bank)
doxycycline The anticonvulsant, phenytoin, decreases the effect of doxycycline (source: Drug Bank)
dyphylline Decreased effect of both products (source: Drug Bank)
dyphylline Decreased effect of both products (source: Drug Bank)
estazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
estazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
estradiol This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
estriol The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
estriol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estriol. (source: Drug Bank)
estrone The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
estrone The enzyme inducer, phenytoin, decreases the effect of the hormone agent, estrone. (source: Drug Bank)
ethinyl estradiol This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
felbamate Increased phenytoin levels and decreased felbamate levels (source: Drug Bank)
felbamate Increased phenytoin levels and decreased felbamate levels (source: Drug Bank)
felodipine The hydantoin decreases the effect of felodipine (source: Drug Bank)
felodipine The hydantoin decreases the effect of felodipine (source: Drug Bank)
fluconazole Fluconazole increases the effect of hydantoin (source: Drug Bank)
fluconazole Fluconazole increases the effect of hydantoin (source: Drug Bank)
fludrocortisone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
fludrocortisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, fludrocortisone. (source: Drug Bank)
fluorouracil Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fluorouracil Fluorouracil increases the effect of hydantoin (source: Drug Bank)
fluoxetine Fluoxetine increases the effect of phenytoin (source: Drug Bank)
fluoxetine Fluoxetine increases the effect of phenytoin (source: Drug Bank)
flurazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
flurazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
fluvoxamine Fluvoxamine increases the effect of hydantoin (source: Drug Bank)
fluvoxamine Fluvoxamine increases the effect of hydantoin (source: Drug Bank)
folic acid folic acid decreases the levels of hydantoin (source: Drug Bank)
furosemide The hydantoin decreases the effect of furosemide (source: Drug Bank)
furosemide The hydantoin decreases the effect of furosemide (source: Drug Bank)
gabapentin Gabapentin increases the effect of hydantoin (source: Drug Bank)
gabapentin Gabapentin increases the effect of hydantoin (source: Drug Bank)
gallamine triethiodide Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
gallamine triethiodide Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
gefitinib This CYP3A4 inducer may reduce gefitinib plasma concentrations and pharmacological effects (source: Drug Bank)
gefitinib The CYP3A4 inducer, phenytoin, may decrease the serum concentration and therapeutic effects of gefitinib. (source: Drug Bank)
hydrocortisone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
hydrocortisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, hydrocortisone. (source: Drug Bank)
imatinib The hydantoin decreases the levels of imatinib (source: Drug Bank)
imatinib The hydantoin decreases the levels of imatinib (source: Drug Bank)
irinotecan The hydantoin decreases the effect of irinotecan (source: Drug Bank)
irinotecan The hydantoin decreases the effect of irinotecan (source: Drug Bank)
isoniazid Isoniazid increases the effect of phenytoin in 20% of patients (source: Drug Bank)
isoniazid Isoniazid increases the effect of phenytoin in 20% of patients (source: Drug Bank)
itraconazole Phenytoin decreases the effect of itraconazole (source: Drug Bank)
itraconazole Phenytoin decreases the effect of itraconazole (source: Drug Bank)
lamotrigine Phenytoin may reduce levels of lamotrigine (source: Drug Bank)
lamotrigine Phenytoin may reduce levels of lamotrigine (source: Drug Bank)
levodopa The hydantoin decreases the effect of levodopa (source: Drug Bank)
levodopa The hydantoin decreases the effect of levodopa (source: Drug Bank)
levonorgestrel Phenytoin decreases the contraceptive effect (source: Drug Bank)
levonorgestrel Phenytoin decreases the contraceptive effect (source: Drug Bank)
lopinavir Levels of both drugs are affected (source: Drug Bank)
lopinavir Levels of both drugs are affected (source: Drug Bank)
lorazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
lorazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
mebendazole The hydantoin decreases the efficiency of mebendazole (source: Drug Bank)
mebendazole The hydantoin decreases the efficiency of mebendazole (source: Drug Bank)
medroxyprogesterone The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
medroxyprogesterone The enzyme inducer, phenytoin, decreases the effect of the hormone, medroxyprogesterone. (source: Drug Bank)
megestrol The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
megestrol The enzyme inducer, phenytoin, decreases the effect of the hormone, megestrol. (source: Drug Bank)
mestranol This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
mestranol This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
methotrexate The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
methoxsalen The hydantoin decreases the effect of psoralene (source: Drug Bank)
methoxsalen The hydantoin decreases the effect of psoralene (source: Drug Bank)
methylprednisolone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
methylprednisolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, methylprednisolone. (source: Drug Bank)
metocurine Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
metocurine Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
metyrapone The combination renders the test invalid (source: Drug Bank)
metyrapone The combination renders the test invalid (source: Drug Bank)
mexiletine The hydantoin decreases the effect of mexiletine (source: Drug Bank)
mexiletine The hydantoin decreases the effect of mexiletine (source: Drug Bank)
midazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
midazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
mirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
mirtazapine The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects (source: Drug Bank)
mivacurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
mivacurium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
nisoldipine Phenytoin decreases the efficiency of nisoldipine (source: Drug Bank)
nisoldipine Phenytoin decreases the efficiency of nisoldipine (source: Drug Bank)
norethindrone This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
norethindrone This product may cause a slight decrease of contraceptive effect (source: Drug Bank)
omeprazole Omeprazole increases the effect of hydantoin (source: Drug Bank)
omeprazole Omeprazole increases the effect of hydantoin (source: Drug Bank)
oxazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
oxazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
oxcarbazepine Oxcarbazepine increases the effect of hydantoin (source: Drug Bank)
oxcarbazepine Oxcarbazepine increases the effect of hydantoin (source: Drug Bank)
oxtriphylline Decreased effect of both products (source: Drug Bank)
oxtriphylline Decreased effect of both products (source: Drug Bank)
oxyphenbutazone The NSAID increases the effect of hydantoin (source: Drug Bank)
oxyphenbutazone The NSAID, oxphenbutazone, may increase the effect of hydantoin of phenytoin. (source: Drug Bank)
pancuronium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
pancuronium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
paramethasone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
paramethasone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, paramethasone. (source: Drug Bank)
phenylbutazone The NSAID increases the effect of hydantoin (source: Drug Bank)
phenylbutazone The NSAID, phenylbutazone, may increase the effect of hydantoin of phenytoin. (source: Drug Bank)
posaconazole Modifications of drug levels for both agents (source: Drug Bank)
posaconazole Modifications of drug levels for both agents (source: Drug Bank)
praziquantel Markedly lower praziquantel levels (source: Drug Bank)
praziquantel Markedly lower praziquantel levels (source: Drug Bank)
prednisolone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
prednisolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisolone. (source: Drug Bank)
prednisone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
prednisone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisone. (source: Drug Bank)
quazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
quazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
quetiapine Phenytoin decreases the effect of quetiapine (source: Drug Bank)
quetiapine Phenytoin decreases the effect of quetiapine (source: Drug Bank)
quinestrol The enzyme inducer decreases the effect of the hormones (source: Drug Bank)
quinestrol The enzyme inducer, phenytoin, decreases the effect of the hormone agent, quinestrol. (source: Drug Bank)
quinidine The anticonvulsant decreases the effect of quinidine (source: Drug Bank)
quinidine The anticonvulsant, phenytoin, decreases the effect of quinidine. (source: Drug Bank)
rifampin Rifampin decreases the effect of hydantoin (source: Drug Bank)
rifampin Rifampin decreases the effect of hydantoin (source: Drug Bank)
sertraline Sertraline increases the effect of hydantoin (source: Drug Bank)
sertraline Sertraline increases the effect of hydantoin (source: Drug Bank)
sirolimus The hydantoin decreases sirolimus levels (source: Drug Bank)
sirolimus The hydantoin decreases sirolimus levels (source: Drug Bank)
sodium Valproate increases the effect of hydantoin (source: Drug Bank)
sodium Valproate increases the effect of hydantoin (source: Drug Bank)
sucralfate Sucralfate decreases the effect of hydantoin (source: Drug Bank)
sucralfate Sucralfate decreases the effect of hydantoin (source: Drug Bank)
sulfadiazine The sulfonamide increases the effect of hydantoin (source: Drug Bank)
sulfadiazine The sulfonamide increases the effect of hydantoin (source: Drug Bank)
sulfamethizole The sulfonamide increases the effect of hydantoin (source: Drug Bank)
sulfamethizole The sulfonamide increases the effect of hydantoin (source: Drug Bank)
sunitinib Possible decrease in sunitinib levels (source: Drug Bank)
sunitinib Possible decrease in sunitinib levels (source: Drug Bank)
tacrolimus The hydantoin decreases the effect of tacrolimus (source: Drug Bank)
tacrolimus The hydantoin decreases the effect of tacrolimus (source: Drug Bank)
telithromycin Telithromycin may possibly increase the agent effect/toxicity (source: Drug Bank)
telithromycin Telithromycin may possibly increase the effect and toxicity of phenytoin. (source: Drug Bank)
temazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
temazepam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
theophylline Decreased effect of both products (source: Drug Bank)
theophylline Decreased effect of both products (source: Drug Bank)
thiotepa Possible increase in thiotepa levels (source: Drug Bank)
thiotepa Possible increase in thiotepa levels (source: Drug Bank)
ticlopidine Ticlopidine increases the effect of hydantoin (source: Drug Bank)
ticlopidine Ticlopidine increases the effect of hydantoin (source: Drug Bank)
topiramate Increased phenytoin/decreased topiramate (source: Drug Bank)
topiramate Increased phenytoin/decreased topiramate (source: Drug Bank)
triamcinolone The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
triamcinolone The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, triamcinolone. (source: Drug Bank)
triazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
triazolam Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
trimethoprim Trimethoprim increases the effect of hydantoin (source: Drug Bank)
trimethoprim Trimethoprim increases the effect of hydantoin (source: Drug Bank)
trioxsalen The hydantoin decreases the effect of psoralene (source: Drug Bank)
trioxsalen The hydantoin decreases the effect of psoralene (source: Drug Bank)
tubocurarine Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
tubocurarine Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
vecuronium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
vecuronium Phenytoin decreases the effect of the muscle relaxant (source: Drug Bank)
vigabatrin Vigabatrin decreases the effect of hydantoin (source: Drug Bank)
vigabatrin Vigabatrin decreases the effect of hydantoin (source: Drug Bank)
vinblastine The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
vinblastine The antineoplasic agent decreases the effect of hydantoin (source: Drug Bank)
voriconazole The hydantoin decreases the effect of voriconazole (source: Drug Bank)
voriconazole The hydantoin decreases the effect of voriconazole (source: Drug Bank)
warfarin Increased hydantoin levels and risk of bleeding (source: Drug Bank)
warfarin Increased hydantoin levels and risk of bleeding (source: Drug Bank)
phenytoin Markedly lower praziquantel levels (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisolone. (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, prednisone. (source: Drug Bank)
phenytoin Phenytoin decreases the effect of quetiapine (source: Drug Bank)
phenytoin Phenytoin decreases the effect of quetiapine (source: Drug Bank)
phenytoin The anticonvulsant decreases the effect of quinidine (source: Drug Bank)
phenytoin The anticonvulsant, phenytoin, decreases the effect of quinidine. (source: Drug Bank)
phenytoin Rifampin decreases the effect of the hydantoin (source: Drug Bank)
phenytoin Rifampin decreases the effect of the hydantoin (source: Drug Bank)
phenytoin Phenytoin may decrease the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Phenytoin therapy is initiated, discontinued or altered. (source: Drug Bank)
phenytoin Telithromycin may possibly increase this agent effect/toxicity (source: Drug Bank)
phenytoin Phenytoin may decrease the plasma concentration of Telithromycin by increasing its metabolism. Consider alternate therapy. (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Phenytoin may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided. (source: Drug Bank)
phenytoin Decreased effect of both products (source: Drug Bank)
phenytoin Decreased effect of both products (source: Drug Bank)
phenytoin Ticlopidine increases the effect of hydantoin (source: Drug Bank)
phenytoin Ticlopidine may decrease the metabolism and clearance of Phenytoin. Consider alternate therapy or monitor for adverse/toxic effects of Phenytoin if Ticlopidine is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin Phenytoin decreases the concentration of Tipranavir. Monitor for decreased Tipranavir efficacy. (source: Drug Bank)
phenytoin Increased risk of nephrotoxicity (source: Drug Bank)
phenytoin Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Phenytoin. Consider alternate therapy or monitor for changes in Phenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Phenytoin. Consider alternate therapy or monitor for changes in Phenytoin therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin Phenytoin may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance. (source: Drug Bank)
phenytoin The CYP3A4 inducer, Phenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenytoin is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin The CYP3A4 inducer, Phenytoin, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Phenytoin is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin The strong CYP2C8 inducer, Phenytoin, may increase the metabolism and clearance of oral Tretinoin. Consider alternate therapy to avoid failure of Tretinoin therapy or monitor for changes in Tretinoin effectiveness and adverse/toxic effects if Phenytoin is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin The enzyme inducer decreases the effect of the corticosteroid (source: Drug Bank)
phenytoin The enzyme inducer, phenytoin, may decrease the effect of the corticosteroid, triamcinolone. (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin Possible increased levels of the hydantoin, decrease of benzodiazepine (source: Drug Bank)
phenytoin The CNS depressants, Triprolidine and Phenytoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
phenytoin The CNS depressants, Triprolidine and Phenytoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy. (source: Drug Bank)
phenytoin Verapamil may increase the serum concentration of Phenytoin by decreasing its metabolism. Monitor for changes in the therapeutic/adverse effects of Phenytoin if Verapamil is initiated, discontinued or dose changed. (source: Drug Bank)
phenytoin Voriconazole may increase the serum concentration of phenytoin by decreasing its metabolism. Phenytoin may increase the serum concentration of voriconazole by increasing its metabolism. Consider alternate antifungal therapy or monitor for voriconazole therapy failure and phenytoin toxicity. (source: Drug Bank)
phenytoin Warfarin may increase the serum concentration of phenytoin possibly by competing for CYP2C9 metabolism. Phenytoin may increase the anticoagulant effect of warfarin. Monitor phenytoin levels, prothrombin time, and therapeutic and adverse effects of both agents during concomitant therapy. (source: Drug Bank)

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Publications related to phenytoin: 130

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Profound reduction in the tamoxifen active metabolite endoxifen in a patient on phenytoin for epilepsy compared with a CYP2D6 genotype matched cohort. Pharmacogenetics and genomics. 2014. Gryn Steven E, et al. PubMed
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Understanding variability with voriconazole using a population pharmacokinetic approach: implications for optimal dosing. The Journal of antimicrobial chemotherapy. 2014. Dolton Michael J, et al. PubMed
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Impact of CYP polymorphisms, ethnicity and sex differences in metabolism on dosing strategies: the case of efavirenz. European journal of clinical pharmacology. 2014. Naidoo Panjasaram, et al. PubMed
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Gene-wide tagging study of the effects of common genetic polymorphisms in the alpha subunits of the GABAA receptor on epilepsy treatment response. Pharmacogenomics. 2013. Hung Chin-Chuan, et al. PubMed
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Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics. 2013. Kaniwa Nahoko, et al. PubMed
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GABRG2, rs211037 is associated with epilepsy susceptibility, but not with antiepileptic drug resistance and febrile seizures. Pharmacogenetics and genomics. 2013. Balan Shabeesh, et al. PubMed
HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013. Cheung Ying-Kit, et al. PubMed
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SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis. Pharmacogenomics. 2013. Haerian Batoul Sadat, et al. PubMed
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Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
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PharmGKB summary: phenytoin pathway. Pharmacogenetics and genomics. 2012. Thorn Caroline F, et al. PubMed
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Neurological toxicity after phenytoin infusion in a pediatric patient with epilepsy: influence of CYP2C9, CYP2C19 and ABCB1 genetic polymorphisms. The pharmacogenomics journal. 2012. Dorado P, et al. PubMed
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Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs. Translational research : the journal of laboratory and clinical medicine. 2012. Neuman Manuela G, et al. PubMed
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Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. Pharmacogenomics. 2012. McCormack Mark, et al. PubMed
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Lack of association between ABCC2 gene variants and treatment response in epilepsy. Pharmacogenomics. 2012. Hilger Eva, et al. PubMed
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Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. Annual review of pharmacology and toxicology. 2012. Bharadwaj Mandvi, et al. PubMed
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PharmGKB summary: very important pharmacogene information for cytochrome P450, family 2, subfamily C, polypeptide 19. Pharmacogenetics and genomics. 2011. Scott Stuart A, et al. PubMed
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Possible role of CYP2C9 & CYP2C19 single nucleotide polymorphisms in drug refractory epilepsy. The Indian journal of medical research. 2011. Lakhan Ram, et al. PubMed
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Genome-Wide Association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe. Orphanet journal of rare diseases. 2011. Genin Emmanuelle, et al. PubMed
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Pharmacogenomic association study on the role of drug metabolizing, drug transporters and drug target gene polymorphisms in drug-resistant epilepsy in a north Indian population. Indian journal of human genetics. 2011. Kumari Ritu, et al. PubMed
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CYP2C9 polymorphism in patients with epilepsy: genotypic frequency analyzes andphenytoin adverse reactions correlation. Arquivos de neuro-psiquiatria. 2011. Twardowschy Carlos Alexandre, et al. PubMed
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Pharmacogenetics of drug-induced birth defects: what is known so far?. Pharmacogenomics. 2011. Wilffert Bob, et al. PubMed
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Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
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SCN1A splice variants exhibit divergent sensitivity to commonly used antiepileptic drugs. Epilepsia. 2011. Thompson Christopher H, et al. PubMed
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Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
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Gene-wide tagging study of the association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy. Pharmacogenomics. 2011. Kwan Patrick, et al. PubMed
HLA-B*1502 genotyping in two Chinese patients with phenytoin-induced Stevens-Johnson syndrome. Epilepsy & behavior : E&B. 2011. Min Fu-Li, et al. PubMed
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A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2011. Depondt C, et al. PubMed
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Phenytoin-induced Stevens-Johnson syndrome with negative HLA-B*1502 allele in mainland China: Two cases. Seizure : the journal of the British Epilepsy Association. 2011. Hu Fa-Yun, et al. PubMed
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Genome-wide association study of serious blistering skin rash caused by drugs. The pharmacogenomics journal. 2011. Shen Y, et al. PubMed
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Influence of CYP2C9 genetic polymorphism and undernourishment on plasma-free phenytoin concentrations in epileptic patients. Therapeutic drug monitoring. 2010. Ramasamy Kesavan, et al. PubMed
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[Development of rapid genotyping methods for single nucleotide polymorphisms of cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19) and their clinical application in pediatric patients with epilepsy]. Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan. 2011. Yamamoto Yoshiaki, et al. PubMed
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Genetic polymorphisms in sex hormone metabolizing genes and drug response in women with epilepsy. Pharmacogenomics. 2010. Grover Sandeep, et al. PubMed
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Transporter hypothesis of drug-resistant epilepsy: challenges for pharmacogenetic approaches. Pharmacogenomics. 2010. Potschka Heidrun. PubMed
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Absence of a general association between ABCB1 genetic variants and response to antiepileptic drugs in epilepsy patients. Biochimie. 2010. Grover Sandeep, et al. PubMed
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Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence-based review. Drug safety : an international journal of medical toxicology and drug experience. 2010. Youngster Ilan, et al. PubMed
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PharmGKB summary: very important pharmacogene information for CYP2B6. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
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Influence of CYP2C9 and CYP2C19 genetic polymorphisms on phenytoin-induced neurological toxicity in Indian epileptic patients. European journal of clinical pharmacology. 2010. Kesavan Ramasamy, et al. PubMed
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Cutaneous adverse drug reactions seen in a tertiary hospital in Johor, Malaysia. International journal of dermatology. 2010. Ding Wen Yi, et al. PubMed
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Genetic profile of patients with epilepsy on first-line antiepileptic drugs and potential directions for personalized treatment. Pharmacogenomics. 2010. Grover Sandeep, et al. PubMed
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Pharmacokinetic and pharmacodynamic interactions between the immunosuppressant sirolimus and the lipid-lowering drug ezetimibe in healthy volunteers. Clinical pharmacology and therapeutics. 2010. Oswald S, et al. PubMed
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What is the role of lidocaine or phenytoin in tricyclic antidepressant-induced cardiotoxicity?. Clinical toxicology (Philadelphia, Pa.). 2010. Foianini Anthony, et al. PubMed
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Cytochrome P450 2C9-CYP2C9. Pharmacogenetics and genomics. 2010. Van Booven Derek, et al. PubMed
Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010. Hung Shuen-Iu, et al. PubMed
CYP2C9*1B promoter polymorphisms, in linkage with CYP2C19*2, affect phenytoin autoinduction of clearance and maintenance dose. The Journal of pharmacology and experimental therapeutics. 2010. Chaudhry Amarjit S, et al. PubMed
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Key factors in the discovery and development of new antiepileptic drugs. Nature reviews. Drug discovery. 2010. Bialer Meir, et al. PubMed
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Maternal EPHX1 polymorphisms and risk of phenytoin-induced congenital malformations. Pharmacogenetics and genomics. 2010. Azzato Elizabeth M, et al. PubMed
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CYP2C9, CYP2C19, and ABCB1 genotype and hospitalization for phenytoin toxicity. Journal of clinical pharmacology. 2009. Hennessy Sean, et al. PubMed
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Warfarin interactions with substances listed in drug information compendia and in the FDA-approved label for warfarin sodium. Clinical pharmacology and therapeutics. 2009. Anthony M, et al. PubMed
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Differential role of sodium channels SCN1A and SCN2A gene polymorphisms with epilepsy and multiple drug resistance in the north Indian population. British journal of clinical pharmacology. 2009. Lakhan Ram, et al. PubMed
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Histone deacetylase inhibitors induce a very broad, pleiotropic anticancer drug resistance phenotype in acute myeloid leukemia cells by modulation of multiple ABC transporter genes. Clinical cancer research : an official journal of the American Association for Cancer Research. 2009. Hauswald Stefanie, et al. PubMed
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CYP2C9 amino acid residues influencing phenytoin turnover and metabolite regio- and stereochemistry. The Journal of pharmacology and experimental therapeutics. 2009. Mosher Carrie M, et al. PubMed
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Genetic Polymorphism of the Human Cytochrome P450 2C9 Gene and Its Clinical Significance. Current drug metabolism. 2009. Wang B, et al. PubMed
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Prediction of the effects of genetic polymorphism on the pharmacokinetics of CYP2C9 substrates from in vitro data. Pharmaceutical research. 2009. Kusama Makiko, et al. PubMed
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Epilepsy pharmacogenetics. Pharmacogenomics. 2009. Kasperavici¿te Dalia, et al. PubMed
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Gene-wide tagging study of association between ABCB1 polymorphisms and multidrug resistance in epilepsy in Han Chinese. Pharmacogenomics. 2009. Kwan Patrick, et al. PubMed
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Genetic determinants of response to clopidogrel and cardiovascular events. The New England journal of medicine. 2009. Simon Tabassome, et al. PubMed
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Redox regulation of multidrug resistance in cancer chemotherapy: molecular mechanisms and therapeutic opportunities. Antioxidants & redox signaling. 2009. Kuo Macus Tien. PubMed
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The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia. 2009. Löscher Wolfgang, et al. PubMed
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No association of ABCB1 polymorphisms with drug-refractory epilepsy in a north Indian population. Epilepsy & behavior : E&B. 2009. Lakhan R, et al. PubMed
Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008. Locharernkul Chaichon, et al. PubMed
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Phenytoin toxicity due to genetic polymorphism. Neurocritical care. 2009. McCluggage Lauren K, et al. PubMed
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Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008. Luna-Tortós Carlos, et al. PubMed
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Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, et al. PubMed
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Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression. Pharmacogenetics and genomics. 2008. Kwan Patrick, et al. PubMed
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Application and interpretation of hPXR screening data: Validation of reporter signal requirements for prediction of clinically relevant CYP3A4 inducers. Biochemical pharmacology. 2008. Cui Xiaoming, et al. PubMed
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Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Zhou S-F. PubMed
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Capecitabine: an overview of the side effects and their management. Anti-cancer drugs. 2008. Saif Muhammad Wasif, et al. PubMed
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Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenetics and genomics. 2008. Hung Chin-Chuan, et al. PubMed
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Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008. Uhr Manfred, et al. PubMed
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Citalopram enantiomers in plasma and cerebrospinal fluid of ABCB1 genotyped depressive patients and clinical response: a pilot study. Pharmacological research : the official journal of the Italian Pharmacological Society. 2008. Nikisch Georg, et al. PubMed
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Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. The Journal of investigative dermatology. 2008. Mockenhaupt Maja, et al. PubMed
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Stereoselective glucuronidation of 5-(4'-hydroxyphenyl)-5-phenylhydantoin by human UDP-glucuronosyltransferase (UGT) 1A1, UGT1A9, and UGT2B15: effects of UGT-UGT interactions. Drug metabolism and disposition: the biological fate of chemicals. 2007. Nakajima Miki, et al. PubMed
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Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics. 2007. Zanger Ulrich M, et al. PubMed
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Therapeutic drug monitoring and clinical outcomes in epileptic Egyptian patients: a gene polymorphism perspective study. Therapeutic drug monitoring. 2007. Ebid Abdel-Hameed I Mohammed, et al. PubMed
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Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. The Journal of pharmacology and experimental therapeutics. 2007. Faucette Stephanie R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007. Marguerite Véronique, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Molecular pharmaceutics. 2007. Collnot Eva-Maria, et al. PubMed
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A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenetics and genomics. 2006. Tate Sarah K, et al. PubMed
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Paradoxical urinary phenytoin metabolite (S)/(R) ratios in CYP2C19*1/*2 patients. Epilepsy research. 2006. Argikar Upendra A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. Journal of chemotherapy (Florence, Italy). 2006. Boruban M C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
ABCB1 polymorphisms influence the response to antiepileptic drugs in Japanese epilepsy patients. Pharmacogenomics. 2006. Seo Takayuki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Gefitinib modulates the function of multiple ATP-binding cassette transporters in vivo. Cancer research. 2006. Leggas Markos, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Impact of P-glycoprotein on clopidogrel absorption. Clinical pharmacology and therapeutics. 2006. Taubert Dirk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Evaluation of 170 xenobiotics as transactivators of human pregnane X receptor (hPXR) and correlation to known CYP3A4 drug interactions. Current drug metabolism. 2006. Sinz Michael, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Single nucleotide polymorphisms in human P-glycoprotein: its impact on drug delivery and disposition. Expert opinion on drug delivery. 2006. Dey Surajit. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
P450 2C18 catalyzes the metabolic bioactivation of phenytoin. Chemical research in toxicology. 2005. Kinobe Robert T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Defining the clinical role of pharmacogenetics in antiepileptic drug therapy. The pharmacogenomics journal. 2006. Dlugos D J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a Black Beninese population. Pharmacogenetics and genomics. 2005. Allabi Aurel C, et al. PubMed
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Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proceedings of the National Academy of Sciences of the United States of America. 2005. Tate Sarah K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC neuroscience. 2005. Awasthi Sanjay, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Phenytoin may increase the efficacy of temozolomide by methylating DNA-repair enzyme, O6-methylguanine-DNA methyltransferase in patients with glioblastoma. Medical hypotheses. 2005. Altundag Ozden, et al. PubMed
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Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Therapeutic drug monitoring. 2004. Hung Chin-Chuan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Influence of lipid lowering fibrates on P-glycoprotein activity in vitro. Biochemical pharmacology. 2004. Ehrhardt Manuela, et al. PubMed
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Genetic polymorphism of cytochrome P450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions. European journal of clinical pharmacology. 2004. Lee Ai-Young, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharmaceutical research. 2004. Hochman Jerome H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clinical pharmacology and therapeutics. 2004. Marzolini Catia, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2C polymorphisms, phenytoin metabolism and gingival overgrowth in epileptic subjects. Life sciences. 2004. Soga Yoshihiko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical relevance of genetic polymorphisms in the human CYP2C9 gene. European journal of clinical investigation. 2003. Schwarz U I. PubMed
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Severe intoxication after phenytoin infusion: a preventable pharmacogenetic adverse reaction. Neurology. 2003. Citerio G, et al. PubMed
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Genetic polymorphisms of the human MDR1 drug transporter. Annual review of pharmacology and toxicology. 2003. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Involvement of multiple UDP-glucuronosyltransferase 1A isoforms in glucuronidation of 5-(4'-hydroxyphenyl)-5-phenylhydantoin in human liver microsomes. Drug metabolism and disposition: the biological fate of chemicals. 2002. Nakajima Miki, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin. Drug metabolism and disposition: the biological fate of chemicals. 2002. Shin Jae-Gook, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers. Clinical pharmacology and therapeutics. 2002. Fischer Tracy L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug metabolism and disposition: the biological fate of chemicals. 2002. Luo Gang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002. Lee Craig R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics. 2001. Kidd R S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Med-psych drug-drug interactions update. Psychosomatics. 2002. Armstrong Scott C, et al. PubMed
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Severe phenytoin intoxication in a subject homozygous for CYP2C9*3. Clinical pharmacology and therapeutics. 2001. Brandolese R, et al. PubMed
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Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics. 2001. Caraco Y, et al. PubMed
The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics. 2001. van der Weide J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn-Schmiedeberg's archives of pharmacology. 2001. Pauli-Magnus C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: roles of cytochromes P450 2C9, 2C19, and 3A4. Drug metabolism and disposition: the biological fate of chemicals. 2000. Komatsu T, et al. PubMed
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Phenytoin metabolism by human cytochrome P450: involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation. Drug metabolism and disposition: the biological fate of chemicals. 2000. Cuttle L, et al. PubMed
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Genetic polymorphism of the CYP2C subfamily and excessive serum phenytoin concentration with central nervous system intoxication. Therapeutic drug monitoring. 2000. Ninomiya H, et al. PubMed
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Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. British journal of clinical pharmacology. 1999. Aynacioglu A S, et al. PubMed
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The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. The Journal of clinical investigation. 1999. Greiner B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annual review of pharmacology and toxicology. 1999. Ambudkar S V, et al. PubMed
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The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia. 1998. Mamiya K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Free radical intermediates of phenytoin and related teratogens. Prostaglandin H synthase-catalyzed bioactivation, electron paramagnetic resonance spectrometry, and photochemical product analysis. The Journal of biological chemistry. 1998. Parman T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Non-monooxygenase cytochromes P450 as potential human autoantigens in anticonvulsant hypersensitivity reactions. Pharmacogenetics. 1998. Leeder J S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica; the fate of foreign compounds in biological systems. 1998. Tassaneeyakul W, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Phenytoin-induced depletion of folate in rats originates in liver and involves a mechanism that does not discriminate folate form. The Journal of nutrition. 1997. Carl G F, et al. PubMed
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Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clinical pharmacology and therapeutics. 1997. Odani A, et al. PubMed
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Competitive, non-competitive and cooperative interactions between substrates of P-glycoprotein as measured by its ATPase activity. Biochimica et biophysica acta. 1997. Litman T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug metabolism and disposition: the biological fate of chemicals. 1996. Bajpai M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. The Journal of pharmacology and experimental therapeutics. 1994. Shimada T, et al. PubMed
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P-glycoprotein structure and evolutionary homologies. Cytotechnology. 1993. Croop J M. PubMed
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Prenatal prediction of risk of the fetal hydantoin syndrome. The New England journal of medicine. 1990. Buehler B A, et al. PubMed
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Influence of phenytoin and phenobarbital on the disposition of a single oral dose of clonazepam. Clinical pharmacology and therapeutics. 1980. Khoo K C, et al. PubMed
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Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency. British medical journal. 1976. Chan T K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
51672-4069-1
DrugBank:
DB00252
ChEBI:
8107
KEGG Compound:
C07443
KEGG Drug:
D00512
PubChem Compound:
1775
PubChem Substance:
148821
46508847
IUPHAR Ligand:
2624
Drugs Product Database (DPD):
780626
ChemSpider:
1710
Therapeutic Targets Database:
DAP000130
FDA Drug Label at DailyMed:
093fd736-5971-47af-b4ef-08c1696cebe8

Clinical Trials

These are trials that mention phenytoin and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.