Fosphenytoin
Pronouncation: (FOSS-FEN-ih-toe-in)Class: Anticonvulsant, Hydantoin
Trade Names:
Cerebyx
- Injection 150 mg (100 mg phenytoin sodium)
- Injection 750 mg (500 mg phenytoin sodium)
Pharmacology
Feedback for Fosphenytoin
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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.
Pharmacokinetics
Absorption
T max is about 30 min. Bioavailability is 100% with IM dosing.
Distribution
Protein binding is 95% to 99%, about 88% for phenytoin. Vd is 4.3 to 10.8 L.
Metabolism
Fosphenytoin converts to phenytoin by hydrolysis. Phenytoin is extensively metabolized in the liver.
Elimination
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 ImpairmentIncreased fraction of unbound phenytoin may occur.
Hepatic Function ImpairmentIncreased fraction of unbound phenytoin may occur.
ElderlyCl decreases about 20% in patients over 70 yr.
HypoalbuminemiaIncreased 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.
Contraindications
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 EpilepticusAdults
IV
Initial/Loading dose15 to 20 mg PE/kg.
Maintenance and Non-Emergent DoseAdults
IV/IM
Loading dose10 to 20ߙmg PE/kg
Maintenance dose4 to 6ߙPE/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.
Storage/Stability
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, sulfonamidesMay increase phenytoin serum concentrations and effects.
Antineoplastic drugs, carbamazepine, diazoxide, enteral nutritional therapy, rifabutin, rifampin, sucralfateMay decrease serum phenytoin concentrations and effects.
Corticosteroids, coumarin anticoagulants, doxycycline, estrogens, felodipine, levodopa, loop diuretics, methadone, oral contraceptives, mexiletine, quinidine, rifabutin, rifampinThe effects of these agents may be impaired.
CyclosporineCyclosporine concentrations may be decreased.
DisopyramideDisopyramide concentrations and bioavailability may be decreased, while anticholinergic actions may be enhanced.
Divalproex sodium, phenobarbital, sodium valproate, valproic acidMay increase or decrease phenytoin concentrations and effects.
Folic acidMay cause folic acid deficiency.
ItraconazoleEffects of itraconazole may be decreased, while those of phenytoin may be increased.
MetyraponePhenytoin may cause subnormal response to metyrapone.
Non-depolarizing muscle relaxantsMay cause these agents to have shorter duration or decreased effects.
PrimidoneMay increase concentrations of primidone and metabolites, increasing the effects.
Sympathomimetics (eg, dopamine)May cause profound hypotension and possibly cardiac arrest.
TheophyllinesEffects of either agents may be decreased.
Incompatibility
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
Cardiovascular
CV collapse; hypotension; vasodilation; tachycardia; atrial and ventricular conduction depression; ventricular fibrillation; hypertension.
CNS
Nystagmus; headache; dizziness; somnolence; ataxia; stupor; incoordination; paresthesia; extrapyramidal syndrome; tremor; agitation; hypesthesia; dysarthria; vertigo; brain edema.
Dermatologic
Pruritus; rash; ecchymosis (IM).
EENT
Diplopia; amblyopia; tinnitus; deafness.
GI
Nausea; vomiting; constipation; tongue disorder; taste perversion; dry mouth.
Metabolic
Hypokalemia.
Respiratory
Pneumonia.
Miscellaneous
Pelvic and back pain; weakness; asthenia; myasthenia; fever; chills; face edema; injection site inflammation.
Precautions
Pregnancy
Category D .
Lactation
Undetermined.
Children
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
Age does not affect fosphenytoin pharmacokinetics. Phenytoin dosing requirements are variable and should be individualized.
Withdrawal
Abrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually.
Overdosage
Symptoms
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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More Fosphenytoin resources:
Fosphenytoin - Includes detailed dosage instructions.
Fosphenytoin Drug Interactions
