Fosphenytoin

A to Z Drug Facts

 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.

 Indications 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.

 Route/Dosage

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).

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Status epilepticus

ADULTS: IV Initial/Loading dose: 15 to 20 mg PE/kg.

Maintenance and non-emergent dose

ADULTS: IV/IM Loading dose: 10 to 20 mg PE/kg. Maintenance dose: 4 to 6 PE/kg/day.

 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: Cyclosporine concentrations may be decreased. Disopyramide: Disopyramide concentrations and bioavailability may be decreased, while anticholinergic actions may be enhanced. Folic acid: May cause folic acid deficiency. Itraconazole: Effects of itraconazole may be decreased, while those of phenytoin may be increased. Metyrapone: Phenytoin may cause subnormal response to metyrapone. Non-depolarizing muscle relaxants: May cause these agents to have shorter duration or decreased effects. Divalproex sodium, phenobarbital, sodium valproate, valproic acid: May increase or decrease phenytoin concentrations and effects. Primidone: May increase concentrations of primidone and metabolites, increasing the effects. Sympathomimetics (eg, dopamine): May cause profound hypotension and possibly cardiac arrest. Theophyllines: Effects of either agents may be decreased. INCOMPATIBILITIES: Do not mix with other drugs.

 Lab Test Interferences 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: 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. DERM: Pruritis; rash; ecchymosis (IM). EENT: Diplopia; amblyopia; tinnitus; deafness. GI: Nausea; vomiting; constipation; tongue disorder; taste perversion; dry mouth. META: Hypokalemia. RESP: Pneumonia. OTHER: 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. Age: Age does not affect fosphenytoin pharmacokinetics. Phenytoin dosing requirements are variable and should be individualized. Special risk patients: Use drug with caution with hepatic or renal impairment, hypotension, severe myocardial insufficiency, alcohol abuse, and porphyria. Withdrawal: Abrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually.

 Administration/Storage

• Do not administer solution if particulate matter or discoloration is noted.
• May use 5% Dextrose or Normal Saline for dilution prior to administration.
• Avoid administering with other IV solutions or medication; fosphenytoin is incompatible with most.
• Administer IV medication no faster than 150 mg/min to prevent hypotension.
• Store in refrigerator at 36° to 46° F. Do not keep at room temperature for > 48 hours.

 Assessment/Interventions

• Obtain patient history, including drug history and any known allergies. Note hepatic impairment and cardiac disease.
• Before initiation of therapy, assess the patient for hepatic or renal disorders, hypotension, alcohol abuse, or porphyria.
• Monitor the BP and ECG continuously during IV administration.
• Observe for side effects including nystagmus, ataxia, drowsiness, nausea, or vomiting, and report to physician.

 Patient/Family Education

• 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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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts