Fosphenytoin sodium CAS 92134-98-0

Introduction：Basic information about Fosphenytoin sodium CAS 92134-98-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Fosphenytoin sodium Basic information

• Product Name: Fosphenytoin sodium
• Synonyms: 5,5-Diphenyl-3-[(phosphonooxy)methyl]-2,4-imidazolidinedione disodium salt;Fosphenytoin Sodium (350 mg);FOSPHENYTOIN SODIUM;(sp-4-2)-5,5-diphenyl-3-((phosphonooxy)methyl)-2,4-imidazolidinedione disodium salt;FOSPENYTOIN;FOSPHENYTOIN DISODIUM SALT;5,5-Diphenyl-3-[[[di(sodiooxy)phosphinyl]oxy]methyl]-1H-imidazole-2,4(3H,5H)-dione;ACC-9653
• CAS: 92134-98-0
• MF: C16H16N2NaO6P
• MW: 386.28
• Product Categories: Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;API
• Mol File: 92134-98-0.mol

Fosphenytoin sodium Chemical Properties

• Melting point: 220° (softens)
• storage temp.: Inert atmosphere,2-8°C
• solubility: H2O: ≥15mg/mL
• form: powder
• color: white to tan
• Water Solubility: H2O: ≥15mg/mL
• InChI: InChI=1S/C16H15N2O6P.Na.H/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);;
• InChIKey: JOJPAZCANKNCBW-UHFFFAOYSA-N
• SMILES: O=C1N(C(=O)NC1(C1C=CC=CC=1)C1C=CC=CC=1)COP(O)(O)=O.[NaH]

Safety Information

• Hazard Codes: T
• Risk Statements: 45-61-22
• Safety Statements: 53-36/37-45
• RIDADR: UN 2811 6.1 / PGIII
• WGK Germany: 3
• HS Code: 2933290000
• Storage Class: 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects
• Hazard Classifications: Acute Tox. 4 Oral Carc. 1B Repr. 1B
• Toxicity: LD50 in mice, rats (mg/kg): 234, 363 i.v. (Smith)

Fosphenytoin sodium Usage And Synthesis

Originator

Cerebyx,Pfizer

Uses

PDE3 (phosphodiesterase 3) inhibitor

Uses

Anti epileptic

Uses

Fosphenytoin sodium is used in the treatment of epileptic seizures.

Manufacturing Process

By action of formaldehyde and hydrochloric acid on 5,5-diphenylhydantoin wasprepared 3-hydroxymethyl-5,5-diphenyl-imidazolidine-2,4-dione which wasconverted by action PCl3 to 3-chloromethyl-5,5-diphenyl-imidazolidine-2,4-dione by action PCl3. Then the chlorine atom was substituted on P(O)(OBz)Ogroup by action of argentum salt of phosphoric acid dibenzyl ester. Removal ofthe protecting groups by hydrogenolysis gives the 2,4-imidazolidinedione, 5,5-diphenyl-3-((phosphonooxy)methyl)- (fosphenytoin).
In practice it is usually used as sodium salt.

Brand name

Cerebyx (Parke-Davis).

Therapeutic Function

Antiepileptic, Anticonvulsant

Biological Activity

Fosphenytoin is a water soluble phenytoin prodrug.

Clinical Use

Control of status epilepticus
Seizures associated with neurosurgery or head injurywhen oral phenytoin is not possible

Drug interactions

Potentially hazardous interactions with other drugs Aminophylline and theophylline: concentration of bothdrugs reduced with aminophylline and theophylline. Analgesics: enhanced effect with NSAIDs;metabolism of methadone accelerated; possiblyincreases pethidine toxicity. Anthelmintics: concentration of albendazole andpraziquantel reduced; concentration of fosphenytoinpossibly increased by levamisole. Anti-arrhythmics: increased concentration withamiodarone; concentration of disopyramide and possiblydronedarone reduced - avoid with dronedarone. Antibacterials: level increased by clarithromycin,chloramphenicol, isoniazid, metronidazole,sulphonamides and trimethoprim (+ antifolateeffect); concentration increased or decreasedby ciprofloxacin; concentration of bedaquiline,doxycycline and telithromycin reduced - avoid withtelithromycin; concentration reduced by rifamycins.
Anticoagulants: increased metabolism of coumarins(reduced effect but also reports of enhancement);possibly reduced apixaban, dabigatran, edoxaban andrivaroxaban concentration - avoid with dabigatran.
Antidepressants: antagonise anticonvulsanteffect; concentration increased by fluoxetine andfluvoxamine and possibly sertraline; concentration ofmianserin, mirtazapine and paroxetine and possiblytricyclics reduced; concentration reduced by St John’swort - avoid.
Antiepileptics: concentration of both drugs reducedwith carbamazepine, concentration may also beincreased by carbamazepine, eslicarbazepine,ethosuximide, oxcarbazepine, stripentol andtopiramate; concentration of ethosuximide, activeoxcarbazepine metabolite, retigabine, rufinamide(concentration of phenytoin possibly increased),topiramate and valproate possibly reduced;concentration of eslicarbazepine, ethosuximide,lamotrigine, perampanel, tiagabine and zonisamidereduced; concentration of phenobarbital often
increased; phenobarbital and valproate may alterconcentration; concentration reduced by vigabatrin.
Antifungals: concentration of ketoconazole,itraconazole, posaconazole, voriconazole and possiblyisavuconazole and caspofungin reduced - avoid withisavuconazole and itraconazole, increase voriconazoledose and possibly caspofungin; levels increased byfluconazole, miconazole and voriconazole - considerreducing fosphenytoin dose.
Antimalarials: avoid with piperaquine withartenimol, mefloquine and pyrimethamine -antagonise anticonvulsant effect; increased antifolateeffect with pyrimethamine.
Antipsychotics: antagonise anticonvulsant effect;possibly reduced aripiprazole concentration- increase aripiprazole dose; metabolism ofclozapine, haloperidol, quetiapine and sertindoleincreased; concentration increased or decreasedwith chlorpromazine; possibly reduces lurasidoneconcentration - avoid.
Antivirals: possibly reduced concentration ofabacavir, boceprevir, daclatasvir, darunavir, dasabuvir,dolutegravir, indinavir, lopinavir, ombitasvir,paritaprevir, ritonavir, saquinavir and simeprevir- avoid with boceprevir, daclatasvir, dasabuvir,ombitasvir, paritaprevir and simeprevir; rilpivirinereduced - avoid; concentration possibly increased byindinavir and ritonavir; concentration increased ordecreased with zidovudine; avoid with elvitegravir,
etravirine and telaprevir.
Apremilast: concentration of apremilast reduced -avoid.
Calcium-channel blockers: levels increased bydiltiazem; concentration of diltiazem, felodipine,isradipine, nimodipine and verapamil reduced; avoidwith isradipine and nimodipine.
Cannabis extract: concentration possibly reduced byphenytoin - avoid.
Ciclosporin: reduced ciclosporin levels.
Cobicistat: concentration of cobicistat possibly reduced.
Corticosteroids: metabolism accelerated (effect reduced)
. Cytotoxics: metabolism possibly inhibited by
fluorouracil; increased antifolate effect withmethotrexate; reduced fosphenytoin absorption;concentration of busulfan, cabozantinib, ceritinib,eribulin, etoposide and imatinib reduced - avoid withcabozantib, ceritinib and imatinib; concentrationpossibly reduced by bosutinib, cisplatin ibrutinib andidelalisib - avoid with ibrutinib and idelalisib; possiblyreduced concentration of axitinib, increase axitinibdose; possibly reduced concentration of crizotinib- avoid; avoid with cabazitaxel, gefitinib, lapatinib,olaparib, panobinostat, vemurafenib and vismodegib;concentration of irinotecan and its active metabolitereduced.
Dexrazoxane: absorption of fosphenytoin possiblyreduced.
Disulfiram: metabolism of fosphenytoin inhibited. Diuretics: concentration increased by acetazolamide;concentration of eplerenone reduced - avoid;increased risk of osteomalacia with carbonic anhydrsesinhibitors; antagonises effect of furosemide.
Guanfacine: concentration of guanfacine possiblyreduced - increase dose of guanfacine.
Hormone antagonists: possibly reducedconcentration of abiraterone - avoid; metabolism oftoremifene accelerated.
Ivacaftor: concentration of ivacaftor possibly reduced- avoid.
Muscle relaxants: long-term use of phenytoin reduceseffects of non-depolarising muscle relaxants, butacute use may enhance effects.
Oestrogens and progestogens: metabolism increased(reduced contraceptive effect).
Orlistat: possibly increased risk of convulsions.
Sulfinpyrazone: concentration increased bysulfinpyrazone.
Ulcer-healing drugs: metabolism inhibited bycimetidine; absorption reduced by sucralfate;
enhanced effect with esomeprazole and omeprazole.
Ulipristal: contraceptive effect possibly reduced - avoid.

Metabolism

Fosphenytoin is rapidly and completely hydrolysedto phenytoin with a conversion half-life of about 15minutes; one mmol of fosphenytoin yields one mmolof phenytoin. Phenytoin is hydroxylated in the liver toinactive metabolites chiefly 5-(4-hydroxyphenyl)-5-phenylhydantoin by an enzyme system which is saturable.Phenytoin undergoes enterohepatic recycling andis excreted in the urine, mainly as its hydroxylatedmetabolite, in either free or conjugated form.

Fosphenytoin sodium Preparation Products And Raw materials

• Raw materials: Formaldehyde