Drug information of Fosphenytoin
Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.
Mechanism of effect
Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. 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.
Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. For every mmol of fosphenytoin administered, one mmol of phenytoin is produced. The pharmacological and toxicological effects of fosphenytoin include those of phenytoin
Half-Life: 15 min (phenytoin)
Peak Plasma Time: 15 min (IM); 3 hr (phenytoin)
Therapeutic phenytoin level: 10-20 mcg/mL
Bioavailability: ~100% IV/IM
Protein Bound: 95-99%; 70-88% (phenytoin)
Vd: 4.3-10.8 L
Metabolite: PhenytoinExcretion: urine (metabolites)
Fosphenytoin is indicated for short-term parenteral administration when other means of phenytoin administration are unavailable, inappropriate or deemed less advantageous. The safety and effectiveness of fosphenytoin in this use has not been systematically evaluated for more than 5 days. Fosphenytoin can be used for the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.
Express all dosing in mg "phenytoin equivalents" (PE); 1 mg PE is equivalent to 1 mg phenytoin sodium.
Maximum IV infusion rate
- Adults: 150 mg PE/min
- Pediatrics: 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower)
Known hypersensitivity to hydantoins
Sinus bradycardia, sinoatrial block, 2nd or 3rd degree AV block, Adams-Stokes syndrome
A history of prior acute hepatotoxicity attributable to fosphenytoin or phenytoin
Coadministration with delavirdine
- Pruritis (40-50%)
- Dizziness (31%)
- Somnolence (20%)
- Ataxia (11%)
- Tinnitus (6-10%)
- Deafness (2-5%)
- Nystagmus (15%)
- Somnolence (6-10%)
- Bruising (7%)
- Pruritis (2-5%)
- Nausea (5%)
- Vomiting (3%)
- Weakness (4%
InteractionsAmlodipine/Atorvastatine , Folinic acid , fentanyl , Ranolazine , Praziquantel , Axitinib , sparfloxacin , Mefloquine , Sarilumab , Doxifluridine , Dexmethylphenidate , Felbamate , Butalbital and Acetaminophen , Ivacaftor , brigatinib , Efavirenz , Copanlisib , Leucovorin , lumacaftor and Ivacaftor , Ulipristal , Dabrafenib , Dolutegravir , Acalabrutinib , Maraviroc , Nintedanib , cobicistat , Delavirdine , Sofosbuvir and velpatasvir , Fostamatinib , Apremilast , Palbociclib , Tasimelteon , trabectedine , Duvelisib , Floxuridine , tezacaftor/ivacaftor , Alpelisib , Temazepam , Edoxaban , Darolutamide , Quazepam , Temsirolimus , ELBASVIR/GRAZOPREVIR , Larotrectinib , gilteritinib , glasdegib , Abemaciclib , Eliglustat , Elvitegravir , Bepridil , bedaquiline , Gefitinib , Dasatinib , Remdesivir , Cannabidiol , lasmiditan , vemurafenib , voxelotor , dichlorphenamide , stiripentol , tecovirimat , Netupitant , secukinumab , Capmatinib , Dienestrol
Drugs that may increase plasma phenytoin concentrations include: acute alcohol intake, amiodarone, chloramphenicol, chlordiazepoxide, cimetidine, diazepam, dicumarol, disulfiram, estrogens, ethosuximide, fluoxetine, H2-antagonists, halothane, isoniazid, methylphenidate, phenothiazines, phenylbutazone, salicylates, succinimides, sulfonamides, tolbutamide, trazodone.
Drugs that may decrease plasma phenytoin concentrations include: carbamazepine, chronic alcohol abuse, reserpine.
- Drugs that may either increase or decrease plasma phenytoin concentrations include: phenobarbital, valproic acid, and sodium valproate.
- Although not a true drug interaction, tricyclic antidepressants may precipitate seizures in susceptible patients and fosphenytoin dosage may need to be adjusted
. • Drugs whose efficacy is impaired by phenytoin include: anticoagulants, corticosteroids, coumarin, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, rifampin, quinidine, theophylline, vitamin D.
Black Box Warnings
Cardiovascular risk associated with rapid infusion rates
- Risk of hypotension and arrhythmias with infusion rates that exceed 150 mg/minute of phenytoin sodium equivalents (PE)
Points of recommendation
Withdrawal of Antiepileptic Drugs
Advise patients not to discontinue use of CEREBYX without consulting with their healthcare provider.
Advise patients that CEREBYX may cause an increase in blood glucose levels
Effects of Alcohol Use and Other Drugs and Over-the-Counter Drug Interactions Caution patients against the use of other drugs or alcoholic beverages without first seeking their physician’s advice.