fosphenytoin (foss-fen-i-toyn) Cerebyx

 Indications

Short-term (5 day) parenteral management of generalized,

tonic-clonic status epilepticus when use of phenytoin

is not feasible. Treatment and prevention of seizures

during neurosurgery when use of phenytoin is not

feasible.

Action

Limits seizure propagation by altering ion transport.

May also decrease synaptic transmission. Fosphenytoin

is rapidly converted to phenytoin, which is responsible

for its pharmacologic effects. Therapeutic Effects:

Diminished seizure activity.

Pharmacokinetics

Absorption: Rapidly converted to phenytoin after IV

administration and completely absorbed after IM administration.

Distribution: Distributes into CSF and other body

tissues and fluids. Enters breast milk; crosses the placenta,

achieving similar maternal/fetal levels. Preferentially

distributes into fatty tissue.

Protein Binding: Fosphenytoin—95–99%; phenytoin—

90–95%.

Metabolism and Excretion: Mostly metabolized

by the liver; minimal amounts excreted in the urine.

Half-life: Fosphenytoin—15 min; phenytoin—22

hr (range 7–42 hr).

TIME/ACTION PROFILE (anticonvulsant effect)

ROUTE ONSET PEAK DURATION

IM unknown 30 min up to 24 hr

IV 15–45 min 15–60 min up to 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Sinus bradycardia,

sinoatrial block, 2nd- or 3rd-degree AV heart

block or Adams-Stokes syndrome; Concurrent use of

delavirdine; Prior acute hepatotoxicity due to fosphenytoin

or phenytoin.

Use Cautiously in: Hepatic or renal disease (qrisk

of adverse reactions; dose reduction recommended for

hepatic impairment); OB: May cause fetal harm (qrisk

of congenital anomalies;qrisk of hemorrhage in newborn

if used at term); Lactation: Present in breast milk;

should weigh risk of potential adverse effects on infant

versus potential benefit to mother.

Exercise Extreme Caution in: Patients positive

for HLA-B*1502 allele (unless exceptional circumstances

exist where benefits clearly outweigh the risks).

Adverse Reactions/Side Effects

CNS: dizziness, drowsiness, nystagmus, agitation, brain

edema, headache, stupor, vertigo. EENT: amblyopia,

deafness, diplopia, tinnitus. CV: hypotension (with

rapid IV administration), tachycardia. GI: dry mouth,

nausea, taste perversion, tongue disorder, vomiting.

Derm: pruritus, purple glove syndrome, rash, STEVENS-

JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS.

MS: back pain. Neuro: ataxia, dysarthria, extrapyramidal

syndrome, hypesthesia, incoordination, paresthesia,

tremor. Misc: DRUG REACTION WITH EOSINOPHILIA

AND SYSTEMIC SYMPTOMS (DRESS), pelvic pain. 

Interactions

Drug-Drug: Maypthe effects of delavirdine, resulting

in loss of virologic response and potential resistant

(concurrent use contraindicated). Disulfiram,

acute ingestion of alcohol, amiodarone, capecitabine,

chloramphenicol, chlordiazepoxide, cimetidine,

diazepam, estrogens, ethosuximide, felbamate,

fluconazole, fluorouracil, fluoxetine,

fluvastatin, fluvoxamine, halothane, isoniazid,

itraconazole, ketoconazole, methylphenidate,

miconazole, omeprazole, oxcarbazepine, phenothiazines,

salicylates, sertraline, succinamides,

sulfonamides, topiramate, trazodone, voriconazole,

and warfarin mayqphenytoin blood levels.

Barbiturates, bleomycin, carbamazepine, carboplatin,

cisplatin, diazoxide, doxorubicin, folic

acid, fosamprenavir, methotrexate, nelfinavir,

reserpine, rifampin, ritonavir, theophylline, vigabatrin,

and chronic ingestion of alcohol maypphenytoin

blood levels. Phenytoin maypthe effects of

albendazole, amiodarone, atorvastatin, benzodiazepines,

carbamazepine, chloramphenicol,

chlorpropamide, clozapine, corticosteroids, cyclosporine,

digoxin, disopyramide, doxycycline,

efavirenz, estrogens, felbamate, fluconazole, fluvastatin,

folic acid, furosemide, indinavir, irinotecan,

itraconazole, ketoconazole, lamotrigine,

lopinavir/ritonavir, methadone, mexiletine, nelfinavir,

nifedipine, nimodpine, nisoldipine, oral

contraceptives, oxcarbazepine, paclitaxel, paroxetine,

posaconazole, propafenone, quetiapine,

quinidine, rifampin, ritonavir, saquinavir, sertraline,

simvastatin, tacrolimus, teniposide, theophylline,

topiramate, tricyclic antidepressants, verapamil

vitamin D, voriconazole, warfarin, and

zonisamide.

Drug-Natural Products: St. John’s wort mayp

levels.

Route/Dosage

Note: Doses of fosphenytoin are expressed as phenytoin

sodium equivalents [PE].

Status Epilepticus

IV (Adults and Children): 15–20 mg PE/kg.

Nonemergent and Maintenance Dosing

IV, IM (Adults and Children 16 yr): Loading

dose—10–20 mg PE/kg. Maintenance dose—4–6

mg PE/kg/day.

IV (Children Birth to 17 yr): Loading dose—10–

15 mg PE/kg. Maintenance dose—2–4 mg PE/kg/

day.

Availability (generic available)

Injection: 50 mg PE/mL.