General

Pronunciation
foss-FEN-i-toyn

Trade Name(s)

• Cerebyx

Pregnancy Category
Category D

Ther. class.
anticonvulsants

Indications

• Short-term (<5 day) parenteral management of generalized, convulsive 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 Effect(s):
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

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity

• Sinus bradycardia, sinoatrial block, 2nd- or 3rd-degree AV heart block or Adams—Stokes syndrome

Use Cautiously in:

• Hepatic or renal disease ( risk of adverse reactions; dose reduction recommended for hepatic impairment)

• OB: Safety not established; may result in fetal hydantoin syndrome if used chronically or hemorrhage in the newborn if used at term

• Lactation: Safety not established

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, rash, STEVENS-JOHNSON SYMDROME.

MS: back pain.

Neuro: ataxia, dysarthria, extrapyramidal syndrome, hypesthesia, incoordination, paresthesia, tremor.

Misc: pelvic pain.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• Disulfiram, acute ingestion of alcohol, amiodarone, ethosuximide, isoniazid, chloramphenicol, sulfonamides, fluoxetine, gabapentin, H2 antagonists, benzodiazepines, omeprazole, ketoconazole, fluconazole, estrogens, succinamides, halothane, methylphenidate, phenothiazines, salicylates, ticlopidine, tolbutamide, topiramate, trazodone, felbamate, and cimetidine may phenytoin blood levels

• Barbiturates, carbamazepine, reserpine, and chronic ingestion of alcohol may phenytoin blood levels

• Phenytoin may the effects of amiodarone, benzodiazepines, carbamazepine, chloramphenicol, corticosteroids, disopyramide, warfarin, felbamate, doxycycline, lamotrigine, oral contraceptives, paroxetine, propafenone, rifampin, ritonavir, quinidine, tacrolimus, theophylline, topiramate, tricyclic antidepressants, zonisamide, methadone, cyclosporine, and estrogens

• IV phenytoin and dopamine may cause additive hypotension

• Additive CNS depression with other CNS depressants, including alcohol, antihistamines, antidepressants, opioids, and sedative/hypnotics

• Antacids may absorption of orally administered phenytoin

• systemic clearance of antileukemic drugs teniposide and methotrexate which has been associated with a worse event free survival, phenytoin use is not recommended in children undergoing chemotherapy for acute lymphocytic leukemia

• Calcium and sucralfate phenytoin absorption

Route/Dosage

• Note: Doses of fosphenytoin are expressed as phenytoin sodium equivalents [PE]

Status Epilepticus

• IV (Adults): 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, IM (Children 10–16 yr): 6–7 mg PE/kg/day.

• IV, IM (Children 7–9 yr): 7–8 mg PE/kg/day.

• IV, IM (Children 4–6 yr): 7.5–9 mg PE/kg/day.

• IV, IM (Children 0.5–3 yr): 8–10 mg PE kg/day.

• IV, IM (Infants): 5 mg PE kg/day.

• IV, IM (Neonates): 5–8 mg PE/kg/day.

Availability

• Injection: 50 mgPE/ml

Assessment

Seizures

• Assess location, duration, frequency, and characteristics of seizure activity. EEG may be monitored periodically during therapy

• Monitor blood pressure, ECG, and respiratory function continuously during administration of fosphenytoin and during period when peak serum phenytoin levels occur (15–30 min after administration)

» Observe patient for development of rash. Discontinue fosphenytoin at the first sign of skin reactions. Serious adverse reactions such as exfoliative, purpuric, or bullous rashes or the development of lupus erythematosus, Stevens-Johnson syndrome, or toxic epidermal necrolysis preclude further use of phenytoin or fosphenytoin. If less serious skin eruptions (measles-like or scarlatiniform) occur, fosphenytoin may be resumed after complete clearing of the rash. If rash reappears, further use of fosphenytoin or phenytoin should be avoided

Lab Test Considerations

• Fosphenytoin contains 0.0037 mmol phosphate per mg PE. Monitor serum phosphate concentrations in patients with renal insufficiency; may cause phosphate concentrations

» May cause serum alkaline phosphatase, GTT, and glucose levels

» Fosphenytoin therapy may be monitored using phenytoin levels. Optimal total plasma phenytoin concentrations are typically 10 — 20 mcg/ml (unbound plasma phenytoin concentrations of 1–2 mcg/ml)

Toxicity and Overdose

• Serum phenytoin levels should not be monitored until complete conversion from fosphenytoin to phenytoin has occurred (2 hr after IV or 4 hr after IM administration)

» Initial signs and symptoms of phenytoin toxicity include nystagmus, ataxia, confusion, nausea, slurred speech, and dizziness

Potential Nursing Diagnoses

• Risk for injury (Indications)

• Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

Do not confuse fosphenytoin (Cerebyx) with celocoxib (Celebrex) or citalopram (Celexa)

» Implement seizure precautions

» When substituting fosphenytoin for oral phenytoin therapy, the same total daily dose may be given as a single dose. Unlike parenteral phenytoin, fosphenytoin may be given safely by the IM route

» The anticonvulsant effect of fosphenytoin is not immediate. Additional measures (including parenteral benzodiazepines) are usually required in the immediate management of status epilepticus. Loading dosage of fosphenytoin should be followed with the institution of maintenance anticonvulsant therapy

IV Adminstration:

• Direct IV:

Diluent: D5W or 0.9% NaCl.
Concentration: 1.5–25 mg PE/ml. May be refrigerated for up to 48 hr

• Rate:
Administer at a rate of <150 mg PE/min in adults and <3 mg/kg/min in children to minimize risk of hypotension

• Y-Site Compatibility:

» lorazepam

» phenobarbital

• Y-Site Incompatibility:

» fenoldopam

» midazolam

• Additive Incompatibility:
Information unavailable. Do not admix with other solutions or medications

Patient/Family Teaching

May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known. Do not resume driving until physician gives clearance based on control of seizure disorder

» Advise patient to carry identification describing disease process and medication regimen at all times

» Advise patient to notify health care professional if skin rash, severe nausea or vomiting, drowsiness, slurred speech, unsteady gait, swollen glands, bleeding or tender gums, yellow skin or eyes, joint pain, fever, sore throat, unusual bleeding or bruising, or persistent headache occurs

» Advise female patients to use an additional nonhormonal method of contraception during therapy and until next menstrual period. Instruct patient to notify health care professional if pregnancy is planned or suspected

» Emphasize the importance of routine exams to monitor progress. Patient should have routine physical exams, especially monitoring skin and lymph nodes, and EEG testing

Evaluation/Desired Outcomes

Decrease or cessation of seizures without excessive sedation

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