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All about: Fosphenytoin

Big Image Pronouncation: (FOSS-FEN-ih-toe-in)
Class: Anticonvulsant, Hydantoin

Trade Names:
- Injection 150 mg (100 mg phenytoin sodium)
- Injection 750 mg (500 mg phenytoin sodium)

Mechanism of Action


Fosphenytoin is a prodrug, which is converted to the active metabolite phenytoin. Appears to act at motor cortex by inhibiting spread of seizure activity. Possibly works by promoting sodium efflux from neurons, thereby stabilizing threshold against hyperexcitability.



T max is about 30 min. Bioavailability is 100% with IM dosing.


Protein binding is 95% to 99%, about 88% for phenytoin. Vd is 4.3 to 10.8 L.


Fosphenytoin converts to phenytoin by hydrolysis. Phenytoin is extensively metabolized in the liver.


The t 1/ 2 is about 15 min; the mean t 1/ 2 is 12 to 28.9 (phenytoin). Fosphenytoin is primarily excreted in the urine as metabolites.

Special Populations

Renal Function Impairment

Increased fraction of unbound phenytoin may occur.

Hepatic Function Impairment

Increased fraction of unbound phenytoin may occur.


Cl decreases about 20% in patients over 70 yr.


Increased fraction of unbound phenytoin may occur.

Indications and Usage

Short-term parenteral administration when other means of phenytoin administration are unavailable, inappropriate, or less advantageous; treatment of generalized convulsive status epilepticus; prevention and treatment of seizures occurring during neurosurgery; short-term substitution for oral phenytoin.


Hypersensitivity to phenytoin or other hydantoins; patients with sinus bradycardia, sino-atrial block, second- and third-degree AV block, and Adams-Stokes syndrome.

Dosage and Administration

To avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium, the fosphenytoin dose is expressed as phenytoin sodium equivalents (PE).

Status Epilepticus


Initial/Loading dose

15 to 20 mg PE/kg.

Maintenance and Non-Emergent Dose


Loading dose

10 to 20 mg PE/kg

Maintenance dose

4 to 6 PE/kg/day.

General Advice

  • Do not administer solution if particulate matter or discoloration is noted.
  • May use D5W or NS for dilution prior to administration.
  • Administer IV no faster than 150 mg/min to prevent hypotension.


Store in refrigerator at 36° to 46° F. Do not keep at room temperature for more than 48 hours.

Drug Interactions

Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, estrogens, felbamate, fluconazole, fluoxetine, isoniazid, oxyphenbutazone, phenacemide, phenylbutazone, succinimides, sulfonamides

May increase phenytoin serum concentrations and effects.

Antineoplastic drugs, carbamazepine, diazoxide, enteral nutritional therapy, rifabutin, rifampin, sucralfate

May decrease serum phenytoin concentrations and effects.

Corticosteroids, coumarin anticoagulants, doxycycline, estrogens, felodipine, levodopa, loop diuretics, methadone, oral contraceptives, mexiletine, quinidine, rifabutin, rifampin

The effects of these agents may be impaired.


Cyclosporine concentrations may be decreased.


Disopyramide concentrations and bioavailability may be decreased, while anticholinergic actions may be enhanced.

Divalproex sodium, phenobarbital, sodium valproate, valproic acid

May increase or decrease phenytoin concentrations and effects.

Folic acid

May cause folic acid deficiency.


Effects of itraconazole may be decreased, while those of phenytoin may be increased.


Phenytoin may cause subnormal response to metyrapone.

Non-depolarizing muscle relaxants

May cause these agents to have shorter duration or decreased effects.


May increase concentrations of primidone and metabolites, increasing the effects.

Sympathomimetics (eg, dopamine)

May cause profound hypotension and possibly cardiac arrest.


Effects of either agents may be decreased.


Do not mix with other drugs.

Laboratory Test Interactions

Fosphenytoin may interfere with metapyrone and dexamethasone tests, causing inaccurate results because of increased metabolism of these agents. Drug may cause decrease in serum levels of protein-bound iodine. It may cause increased levels of glucose, alkaline phosphatase, and gamma glutamyl-transpeptidase.

Adverse Reactions


CV collapse; hypotension; vasodilation; tachycardia; atrial and ventricular conduction depression; ventricular fibrillation; hypertension.


Nystagmus; headache; dizziness; somnolence; ataxia; stupor; incoordination; paresthesia; extrapyramidal syndrome; tremor; agitation; hypesthesia; dysarthria; vertigo; brain edema.


Pruritus; rash; ecchymosis (IM).


Diplopia; amblyopia; tinnitus; deafness.


Nausea; vomiting; constipation; tongue disorder; taste perversion; dry mouth.






Pelvic and back pain; weakness; asthenia; myasthenia; fever; chills; face edema; injection site inflammation.



Category D .




Safety and efficacy not established.

Special Risk Patients

Use drug with caution with hepatic or renal impairment, hypotension, severe myocardial insufficiency, alcohol abuse, and porphyria.


Age does not affect fosphenytoin pharmacokinetics. Phenytoin dosing requirements are variable and should be individualized.


Abrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually.



Nystagmus, ataxia, dysarthria, hypotension, diminished mental capacity, coma, unresponsive pupils, respiratory and cardiovascular depression.

Patient Information

  • Explain to family and patient that the medication is a short-term substitute for the regular use of phenytoin.
  • Explain to family that sedation or drowsiness might occur as a result of the medication.
  • Avoid alcohol or other CNS drugs while taking this medication.
  • Never suddenly discontinue the medication; may lead to status epilepticus.
  • Instruct patient what to do in case of a missed dose.

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