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Details

Stereochemistry ACHIRAL
Molecular Formula C16H13N2O6P.2Na
Molecular Weight 406.2375
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSPHENYTOIN SODIUM

SMILES

[Na+].[Na+].[O-]P([O-])(=O)OCN1C(=O)NC(C1=O)(C2=CC=CC=C2)C3=CC=CC=C3

InChI

InChIKey=GQPXYJNXTAFDLT-UHFFFAOYSA-L
InChI=1S/C16H15N2O6P.2Na/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23;;/h1-10H,11H2,(H,17,20)(H2,21,22,23);;/q;2*+1/p-2

HIDE SMILES / InChI

Molecular Formula Na
Molecular Weight 22.9898
Charge 1
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C16H13N2O6P
Molecular Weight 360.258
Charge -2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020450s020lbl.pdf

Phenytoin is an anti-epileptic drug. Phenytoin has been used with much clinical success against all types of epileptiform seizures, except petit mal epilepsy. Phenytoin is a available for oral administration (tablets, capsules, suspension). CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. Although several potential targets for phenytoin action have been identified within the CNS (Na-K-ATPase, the GABAA receptor complex, ionotropic glutamate receptors, calcium channels and sigma binding sites) to date, though, the best evidence hinges on the inhibition of voltage-sensitive Na+ channels in the plasma membrane of neurons undergoing seizure activity.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DILANTIN-125

Approved Use

Dilantin (phenytoin) is indicated for the control of tonic-clonic (grand mal) and psychomotor (temporal lobe) seizures

Launch Date

1953
Primary
CEREBYX

Approved Use

CEREBYX is indicated for the control of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. CEREBYX can also be substituted, short-term, for oral phenytoin. CEREBYX should be used only when oral phenytoin administration is not possible. CEREBYX must not be given orally.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.176 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENYTOIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32.172 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENYTOIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.49 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PHENYTOIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
600 mg single, oral
Highest studied dose
unhealthy, 31 years
n = 15
Health Status: unhealthy
Condition: epilepsy
Age Group: 31 years
Sex: M+F
Population Size: 15
Sources:
20 g single, oral
Overdose
Dose: 20 g
Route: oral
Route: single
Dose: 20 g
Co-administed with::
glibenclamide(500 mg)
Sources:
unhealthy, 41 years
n = 1
Health Status: unhealthy
Age Group: 41 years
Sex: F
Population Size: 1
Sources:
Other AEs: Sinus bradycardia, Hypotension...
Other AEs:
Sinus bradycardia (1 patient)
Hypotension (severe, 1 patient)
Sources:
5 g single, oral
Overdose
Dose: 5 g
Route: oral
Route: single
Dose: 5 g
Sources:
unhealthy, 49 years
n = 1
Health Status: unhealthy
Age Group: 49 years
Sex: M
Population Size: 1
Sources:
Other AEs: Acute respiratory failure...
Other AEs:
Acute respiratory failure (1 patient)
Sources:
60 mg/kg multiple, intravenous (total)
Overdose
Dose: 60 mg/kg
Route: intravenous
Route: multiple
Dose: 60 mg/kg
Sources:
unhealthy, 7 years
n = 1
Health Status: unhealthy
Age Group: 7 years
Sex: M
Population Size: 1
Sources:
Other AEs: Encephalopathy...
Other AEs:
Encephalopathy (1 patient)
Sources:
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Other AEs: Nystagmus, Ataxia...
Other AEs:
Nystagmus (grade 5)
Ataxia (grade 5)
Dysarthria (grade 5)
Tremor (grade 5)
Hyperreflexia (grade 5)
Lethargy (grade 5)
Slurred speech (grade 5)
Blurred vision (grade 5)
Nausea (grade 5)
Vomiting (grade 5)
Sources:
10 mg/kg single, intramuscular (starting)
Dose: 10 mg/kg
Route: intramuscular
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
Other AEs: Hypotension, Cardiac arrhythmias...
Other AEs:
Hypotension (severe)
Cardiac arrhythmias
Sources:
10 mg/kg single, intravenous (starting)
Dose: 10 mg/kg
Route: intravenous
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
Other AEs: Hypotension, Cardiac arrhythmias...
Other AEs:
Hypotension (severe)
Cardiac arrhythmias
Sources:
AEs

AEs

AESignificanceDosePopulation
Sinus bradycardia 1 patient
20 g single, oral
Overdose
Dose: 20 g
Route: oral
Route: single
Dose: 20 g
Co-administed with::
glibenclamide(500 mg)
Sources:
unhealthy, 41 years
n = 1
Health Status: unhealthy
Age Group: 41 years
Sex: F
Population Size: 1
Sources:
Hypotension severe, 1 patient
20 g single, oral
Overdose
Dose: 20 g
Route: oral
Route: single
Dose: 20 g
Co-administed with::
glibenclamide(500 mg)
Sources:
unhealthy, 41 years
n = 1
Health Status: unhealthy
Age Group: 41 years
Sex: F
Population Size: 1
Sources:
Acute respiratory failure 1 patient
5 g single, oral
Overdose
Dose: 5 g
Route: oral
Route: single
Dose: 5 g
Sources:
unhealthy, 49 years
n = 1
Health Status: unhealthy
Age Group: 49 years
Sex: M
Population Size: 1
Sources:
Encephalopathy 1 patient
60 mg/kg multiple, intravenous (total)
Overdose
Dose: 60 mg/kg
Route: intravenous
Route: multiple
Dose: 60 mg/kg
Sources:
unhealthy, 7 years
n = 1
Health Status: unhealthy
Age Group: 7 years
Sex: M
Population Size: 1
Sources:
Ataxia grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Blurred vision grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Dysarthria grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Hyperreflexia grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Lethargy grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Nausea grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Nystagmus grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Slurred speech grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Tremor grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Vomiting grade 5
2 g single, oral
Overdose
Dose: 2 g
Route: oral
Route: single
Dose: 2 g
Sources:
unhealthy, adult
Cardiac arrhythmias
10 mg/kg single, intramuscular (starting)
Dose: 10 mg/kg
Route: intramuscular
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
Hypotension severe
10 mg/kg single, intramuscular (starting)
Dose: 10 mg/kg
Route: intramuscular
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
Cardiac arrhythmias
10 mg/kg single, intravenous (starting)
Dose: 10 mg/kg
Route: intravenous
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
Hypotension severe
10 mg/kg single, intravenous (starting)
Dose: 10 mg/kg
Route: intravenous
Route: single
Dose: 10 mg/kg
Sources:
unhealthy, adult
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
weak
yes [IC50 145 uM]
yes [IC50 280 uM]
yes [IC50 607 uM]
yes
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=10
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=10
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=11
Page: 46.0
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=11
yes
yes (co-administration study)
Comment: mean AUC(0-24) of losartan was insignificantly increased by 17% when losartan was coadministered with phenytoin. See more on https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
yes
yes
yes
likely (co-administration study)
Comment: See https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page=9
yes
yes (co-administration study)
Comment: Coadministration of losartan had no effect on the pharmacokinetics of phenytoin. See more on https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/084427s042lbl.pdf#page8
Page: 8.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Procainamide and phenytoin. Comparative study of their antiarrhythmic effects at apparent therapeutic plasma levels.
1975 Jul
Anticonvulsant-induced dyskinesias: a comparison with dyskinesias induced by neuroleptics.
1976 Dec
Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine.
1978 Sep 15
Spasticity due to phenytoin toxicity.
1979 Mar 10
Assessment of colour vision in epileptic patients exposed to single-drug therapy.
1999
A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants.
1999 Aug
Interaction between phenytoin and ciprofloxacin.
1999 Feb
Cognitive deterioration associated with focal cortical dysplasia.
1999 Jan
Distinct features of seizures induced by cocaine and amphetamine analogs.
1999 Jul 21
Dyskinesia induced by phenytoin.
1999 Jun
[Atrioventricular junctional arrhythmia due to oral phenytoin intoxication].
1999 Mar 15
Systemic vasculitis associated with long-term phenytoin therapy.
1999 Mar 26
Tuberous sclerosis associated with MDR1 gene expression and drug-resistant epilepsy.
1999 Oct
Fetal anticonvulsant syndrome and mutation in the maternal MTHFR gene.
1999 Sep
Images in clinical medicine. Gingival hyperplasia induced by phenytoin.
2000 Feb 3
Phenytoin poisoning after using Chinese proprietary medicines.
2000 Jul
Refractory idiopathic absence status epilepticus: A probable paradoxical effect of phenytoin and carbamazepine.
2000 Jul
Incidence of intravenous site reactions in neurotrauma patients receiving valproate or phenytoin.
2000 Jun
Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis.
2000 Jun
Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice.
2000 Sep 15
II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients.
2001
Inhibition of phenytoin hydroxylation in human liver microsomes by several selective serotonin re-uptake inhibitors.
2001 Apr
Fosphenytoin: pharmacokinetics and tolerance of intramuscular loading doses.
2001 Feb
The effects of concomitant phenytoin administration on the steady-state pharmacokinetics of quetiapine.
2001 Feb
Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.
2001 Feb
Interferon-alpha2a and 13-cis-retinoic acid with radiation treatment for high-grade glioma.
2001 Jan
Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors.
2001 Jan
Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line.
2001 Jan
Ritonavir-induced carbamazepine toxicity.
2001 Jan
Treatment of nonfebrile status epilepticus in Rochester, Minn, from 1965 through 1984.
2001 Jan
Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices.
2001 Jan
Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems.
2001 Jan 5
N6-cyclohexyladenosine and 3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid enhance the effect of antiepileptic drugs against induced seizures in mice.
2001 Jan-Apr
Volume-selective proton MR spectroscopy for in-vitro quantification of anticonvulsants.
2001 Mar
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice.
2001 Mar
Phenytoin-induced cleft palate: evidence for embryonic cardiac bradyarrhythmia due to inhibition of delayed rectifier K+ channels resulting in hypoxia-reoxygenation damage.
2001 Mar
Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus.
2017 Jun
Patents

Sample Use Guides

Dilantin-125® (Phenytoin Oral Suspension, USP), each 5 ml of suspension contains 125 mg of phenytoin: Patients who have received no previous treatment may be started on one teaspoonful (5 mL) of Dilantin-125 Suspension three times daily, and the dose is then adjusted to suit individual requirements. An increase to five teaspoonfuls daily may be made, if necessary. CEREBYX® (fosphenytoin sodium injection) is a prodrug intended for parenteral administration; its active metabolite is phenytoin. 1.5 mg of fosphenytoin sodium is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE). CEREBYX should be used only when oral phenytoin administration is not possible. Dosage (Status Epilepticus): The loading dose of CEREBYX is 15 to 20 mg PE/kg administered at 100 to 150 mg PE/min.
Route of Administration: Other
Exposure of human adult keratinocytes (HaCaT cells) for 48 h to alkyd nanoemulsions producing phenytoin concentrations of 3.125-200 μg/mL resulted in relative cell viability readings using tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide of 100% confirming nontoxicity and suggesting cell proliferation activity.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:05:57 GMT 2023
Edited
by admin
on Fri Dec 15 15:05:57 GMT 2023
Record UNII
7VLR55452Z
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSPHENYTOIN SODIUM
MART.   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN  
Official Name English
PRO-EPANUTIN
Brand Name English
FOSPHENYTOIN DISODIUM SALT [MI]
Common Name English
CI 982
Code English
ACC-9653-010 (SODIUM SALT)
Code English
FOSPHENYTOIN SODIUM [VANDF]
Common Name English
Fosphenytoin sodium [WHO-DD]
Common Name English
CI-982
Code English
FOSPHENYTOIN SODIUM [USP IMPURITY]
Common Name English
FOSPHENYTOIN SODIUM [ORANGE BOOK]
Common Name English
FOSPHENYTOIN SODIUM [USAN]
Common Name English
FOSPHENYTOIN SODIUM [USP MONOGRAPH]
Common Name English
CEREBYX
Brand Name English
FOSPHENYTOIN SODIUM [MART.]
Common Name English
2,4-IMIDAZOLIDINEDIONE, 5,5-DIPHENYL-3-((PHOSPHONOOXY)METHYL)-, DISODIUM SALT
Common Name English
FOSPHENYTOIN SODIUM [USP-RS]
Common Name English
3-(Hydroxymethyl)-5,5-diphenylhydantoin, disodium phosphate (ester)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C264
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
Code System Code Type Description
FDA UNII
7VLR55452Z
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
RXCUI
82806
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY RxNorm
PUBCHEM
56338
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
DAILYMED
7VLR55452Z
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
EVMPD
SUB13919MIG
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
RS_ITEM_NUM
1286366
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
SMS_ID
100000089993
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
USAN
AA-110
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
CAS
92134-98-0
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
DRUG BANK
DBSALT000296
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
EPA CompTox
DTXSID1044271
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
ChEMBL
CHEMBL1201336
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
MERCK INDEX
m5555
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY Merck Index
NCI_THESAURUS
C47543
Created by admin on Fri Dec 15 15:05:57 GMT 2023 , Edited by admin on Fri Dec 15 15:05:57 GMT 2023
PRIMARY
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