Fosphenytoin Sodium (fosphenytoin sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Fosphenytoin sodium, a prodrug of phenytoin, is a hydantoin-derivative anticonvulsant.
Fosphenytoin sodium is a hydantoin-derivative anticonvulsant. Fosphenytoin sodium, a water-soluble phosphate ester of phenytoin, is a prodrug and has little, if any, anticonvulsant activity until hydrolyzed in vivo to phenytoin. The pharmacologic effects of fosphenytoin are attributed to phenytoin.
The exact mechanism of action has not been established, but may be due to voltage-dependent blockade of membrane sodium channels, resulting in a reduction in sustained high-frequency neuronal discharges.
Following parenteral administration, fosphenytoin sodium is rapidly hydrolyzed (by nonspecific phosphatases) in blood and other tissues (conversion half-life of approximately 8-15 minutes after IV administration) to phenytoin, phosphate, and formaldehyde (subsequently converted to formate). While phosphate and formaldehyde (formate) have potentially important biologic effects, these effects occur at concentrations substantially higher than those attained with recommended dosages of fosphenytoin.
The dose and concentration of fosphenytoin sodium are expressed in terms of phenytoin sodium equivalents (PE) in order to avoid the need for molecular weight-based adjustments when converting from fosphenytoin sodium to phenytoin sodium or vice versa. (See Dosage and Administration: Dosage.)
IV administration of a 15- to 20-mg PE/kg (about 1200 mg PE) loading dose of fosphenytoin sodium at a rate of 100-150 mg PE/minute in adults results (within about 10-30 minutes) in therapeutic plasma concentrations of unbound phenytoin of about 1-2 mcg/mL, which are similar to those achieved with an equivalent dose (15-20 mg/kg; about 1200 mg) of phenytoin sodium administered IV at a rate of 50 mg/minute.
For further information on chemistry, pharmacology, and pharmacokinetics, see Phenytoin 28:12.12 and see the Anticonvulsants General Statement 28:12.
Generic name: fosphenytoin sodium
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Fosphenytoin Sodium
Indications
The following indications are listed for Fosphenytoin Sodium:
- Complex-Partial Epilepsy
- Epilepsy
- Prevention Of Seizures Following Cranial Trauma Or Surgery
- Seizure Occurring During Neurosurgery
- Status Epilepticus
- Tonic-Clonic Epilepsy
Also known as: Automatic Epilepsy, Complex Focal Epilepsy, Complex Focal Seizures, Complex Local Seizures, Complex Partial Epilepsy, Complex Partial Seizures, Complex Psychomotor Epilepsy, Complex Psychomotor Seizure, Complex Temporal Lobe Epilepsy, Complex Temporal Lobe Seizures, Epileptic Disorder, Grand Mal Epilepsy, Haut Mal Epilepsy, Major Epilepsy, Prevention Of Seizure After Head Trauma Or Brain Surgery, Psychic Epilepsy, Psychomotor Epilepsy, Psychomotor Seizure, Temporal Lobe Epilepsy, Temporal Lobe Seizure.
Dosing
Dosage of fosphenytoin sodium is expressed in terms of phenytoin sodium equivalents (PE); 1.5 mg of fosphenytoin sodium is equivalent to 1 mg of phenytoin sodium and is referred to as 1 mg PE. (See Dosage and Administration: General.) IV and IM dosages of fosphenytoin sodium (in terms of PE) are the same, and total daily doses of parenteral fosphenytoin sodium (in terms of PE) generally are equivalent to those of oral phenytoin sodium.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
The following drug interaction information is based principally on interactions that are known or expected to occur with phenytoin. Because phenytoin is the active metabolite of fosphenytoin, the same drug interactions are expected to occur with fosphenytoin.
Phenytoin is involved in multiple drug interactions because of its extensive plasma protein binding, saturable metabolism, and potent hepatic enzyme-inducing properties.
No drugs are known to interfere with the conversion of fosphenytoin to phenytoin.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
History of hypersensitivity to fosphenytoin or any ingredient in the formulation, phenytoin, or other hydantoins.
Sinus bradycardia, sinoatrial block, second- or third-degree atrioventricular (AV) block, or Adams-Stokes syndrome.
History of prior acute hepatotoxicity with fosphenytoin or phenytoin.
Concomitant use with delavirdine.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects occurring in 2% or more of patients receiving fosphenytoin include nystagmus, dizziness, pruritus, paresthesia, headache, somnolence, and ataxia. Sensory disturbances such as paresthesia and pruritus have been reported more frequently in patients receiving IV fosphenytoin than in those receiving IV phenytoin.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of fosphenytoin have been established for the treatment of generalized tonic-clonic status epilepticus and for the prevention and treatment of seizures occurring during neurosurgery in pediatric patients of all age groups.
Use of phenytoin during pregnancy has been associated with an increased risk of congenital malformations and other adverse developmental outcomes. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Reported cases of malignancies, including neuroblastoma, have occurred in children whose mothers received phenytoin during pregnancy.
Because of altered pharmacokinetics of phenytoin during pregnancy, serum concentrations of phenytoin may decline, possibly increasing the frequency of seizures in pregnant women receiving fosphenytoin. If fosphenytoin is administered during pregnancy, serum phenytoin concentrations should be monitored and dosage of fosphenytoin should be adjusted accordingly. (See Dosage and Administration: Special Populations.) Because of altered protein binding, phenytoin concentration monitoring in pregnant women should be based on the unbound (free) phenytoin fraction.
Women who are pregnant while receiving fosphenytoin should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334; registry information also is available at http://www.aedpregnancyregistry.org.
It is not known whether fosphenytoin is distributed into milk; however, phenytoin is distributed into milk. The known benefits of breast-feeding should be considered along with the woman's clinical need for fosphenytoin and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.
Fosphenytoin has not been evaluated systematically in geriatric patients. The pharmacokinetic profile of fosphenytoin in geriatric adults is similar to that in younger adults. However, clearance of phenytoin may be reduced in geriatric patients (20% less in patients older than 70 years of age relative to that in adults 20-30 years of age). (See Dosage and Administration: Special Populations.)
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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