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|Fosphenytoin |
Drugs search, click the first letter of a drug name: | A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | 1 | 2 | 3 | 4 | 5 | 6 | 8 | 9 Home FosphenytoinPronouncation: (FOSS-FEN-ih-toe-in)Class: Anticonvulsant, Hydantoin Trade Names: Mechanism of ActionPharmacologyFosphenytoin 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. PharmacokineticsAbsorptionT max is about 30 min. Bioavailability is 100% with IM dosing. DistributionProtein binding is 95% to 99%, about 88% for phenytoin. Vd is 4.3 to 10.8 L. MetabolismFosphenytoin converts to phenytoin by hydrolysis. Phenytoin is extensively metabolized in the liver. EliminationThe t 1/ 2 is about 15 min; the mean t 1/ 2 is 12 to 28.9 hr (phenytoin). Fosphenytoin is primarily excreted in the urine as metabolites. Special PopulationsRenal 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 UsageShort-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. ContraindicationsHypersensitivity to phenytoin or other hydantoins; patients with sinus bradycardia, sino-atrial block, second- and third-degree AV block, and Adams-Stokes syndrome. Dosage and AdministrationTo 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 20 mg PE/kg Maintenance dose4 to 6 PE/kg/day. General Advice
Storage/StabilityStore in refrigerator at 36° to 46° F. Do not keep at room temperature for more than 48 hr. Drug InteractionsAmiodarone, 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. IncompatibilityDo not mix with other drugs. Laboratory Test InteractionsFosphenytoin 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 ReactionsCardiovascularCV collapse; hypotension; vasodilation; tachycardia; atrial and ventricular conduction depression; ventricular fibrillation; hypertension. CNSNystagmus; headache; dizziness; somnolence; ataxia; stupor; incoordination; paresthesia; extrapyramidal syndrome; tremor; agitation; hypesthesia; dysarthria; vertigo; brain edema. DermatologicPruritus; rash; ecchymosis (IM). EENTDiplopia; amblyopia; tinnitus; deafness. GINausea; vomiting; constipation; tongue disorder; taste perversion; dry mouth. MetabolicHypokalemia. RespiratoryPneumonia. MiscellaneousPelvic and back pain; weakness; asthenia; myasthenia; fever; chills; face edema; injection site inflammation. PrecautionsPregnancyCategory D . LactationUndetermined. ChildrenSafety and efficacy not established. Special Risk PatientsUse drug with caution with hepatic or renal impairment, hypotension, severe myocardial insufficiency, alcohol abuse, and porphyria. AgeAge does not affect fosphenytoin pharmacokinetics. Phenytoin dosing requirements are variable and should be individualized. WithdrawalAbrupt withdrawal may precipitate status epilepticus. Dosage must be reduced or other anticonvulsant medicine substituted gradually. OverdosageSymptomsNystagmus, ataxia, dysarthria, hypotension, diminished mental capacity, coma, unresponsive pupils, respiratory and cardiovascular depression. Patient Information
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