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Non-Critical Care Areas

All Critical Care Areas

FOSPHENYTOIN (CEREBYX)
NOTE: Fosphenytoin sodium dose and concentration should always be expressed in
terms of phenytoin sodium equivalents (PE).
Do not confuse fosphenytoin with phenytoin (Dilantin)

ROUTES OF ADMINISTRATION
Slow IV push, IVPB or IM injection

METHODS FOR IV ADMINISTRATION

1. Fosphenytoin must always be prescribed and dispensed in terms of phenytoin sodium

equivalents (PE). Inadvertent overdoses and deaths have occurred due to misinterpretation
of the concentration.

2. Fosphenytoin injection is available in a concentration of 50 mg PE/mL. Note: this is the same

concentration as the phenytoin sodium injectable product.

3. IV administration:
Dilute in D5W or NS to a concentration between 1.5 to 25 mg PE/mL, depending on whether it is
to be given IVPB or slow IVP.
Administer at a rate of 50 to 150 mg PE/min. Maximum rate of infusion is 150 mg PE/minute
due to the risk of hypotension with higher rates
Maintenance dosing:
Initial maintenance dose: usually 100 mg every 8 hours ( dose range: 4 6 mg PE/kg/day)
Status epilepticus:
Loading dose: Usual range is 750 1500 mg PE (based on 15 20 mg PE/kg) to be given
IVPB at a rate of 100 to 150 mg PE/minutes
Maintenance doses of fosphenytoin should follow
Nonemergent loading:
Loading dose: Usual range is 500 mg 1500 mg (based on 10 20 mg PE/kg) given IVPB at
a rate up to 150 mg PE/minute
Suggested fosphenytoin dilution volumes and rates of administration:

IV Push

Dose
100 mg
101 mg 300 mg
301 mg 600 mg
601 mg 1000 mg
1001 mg 1250 mg
1251 mg 1500 mg

Volume of
D5W or NS
4 mL
-

IVPB

Rate
2 minutes
-

Volume of
D5W or NS
10 mL
15 mL
25 mL
40 mL
50 mL
60 mL

Rate
10 minutes
10 minutes
10 minutes
10 minutes
13 minutes
15 minutes

4. IM administration:
IM fosphenytoin may be administered as a single daily dose in 1 or 2 injection sites
IV administration is the preferred route in the treatment of status epilepticus since therapeutic

concentrations may be reached more quickly.

FOSPHENYTOIN (Cerebyx)

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5. Oral phenytoin to IM or IV fosphenytoin:

Fosphenytoin can be substituted for oral phenytoin at the same total daily dose.

INDICATIONS FOR IV USE

1. Status epilepticus (usually in conjunction with benzodiazepines)

2. Seizures: for treatment or prophylaxis

MONITORING PARAMETERS

1. IV loading doses: continuous ECG and vital signs during the infusion for 30 minutes after the

infusion (time of maximum serum concentrations).

2. Phenytoin total and unbound serum concentrations: therapeutic total phenytoin concentration: 10
20 mcg/mL; unbound phenytoin concentration: 1 2 mcg/mL. Following fosphenytoin
administration, levels should not be obtained until conversion to phenytoin is complete
approximately 2 hours after the end of IV infusion and 4 hours after IM injection.

POTENTIAL PROBLEMS WITH ADMINISTRATION

1. Sensory disturbances (e.g., systemic burning, pruritus, and/or paresthesia): reported in up to 64% of

2.
3.

4.
5.
6.

patients administered doses of 15 mg PE/kg at 150 mg PE/min. The groin is the most frequent
location of discomfort. Effects usually occur within several minutes of the start of infusion and
resolve within 10 minutes after completion. However some patients reported symptoms for hours.
Patients administered fosphenytoin at doses of 20 mg PE/kg at 150 mg PE/min are expected to
experience some degree of discomfort.
Itching: mild to moderate local itching reported in 23% of patients receiving IM fosphenytoin.
Hypotension and cardiac effects: hypotension may occur after IV administration of high does at high
rates of administration. Following the administration of phenytoin, severe cardiovascular reactions
and fatalities have been reported with atrial and ventricular conduction depression and ventricular
fibrillation. Severe complications are more common in elderly or gravely ill patients.
Acute hepatoxicity: usually associated with a hypersensitivity syndrome characterized by fever, skin
eruptions, and lymphadenopathy and usually occur within the first 2 months of treatment.
Infusion reactions: In clinical trials only 9% of patients reported pain and burning at infusion site with
fosphenytoin versus 90% of patients who received phenytoin.
Other common adverse effects: nystagmus, dizziness, headache, somnolence and ataxia.

TREATMENT OF ADVERSE SIDE EFFECTS

1. Hypotension or other cardiac effects: reduce the rate of administration or discontinue therapy.
2. Sensory disturbances: the occurrence and intensity of the discomfort can be lessened by reducing the

rate of administration.
3. Rash: discontinue therapy. If the rash is exfoliative, purpuric, or bullous, or if lupus erythematosus,
Stevens-Johnson syndrome, or toxic epidermal necrolysis is suspected, use of this drug should not be
resumed. If the rash is of a milder type (measles-like or scarlatiniform), therapy may be resumed after the
rash has cleared. However if the rash returns with rechallenge, further fosphenytoin or phenytoin use is
contraindicated.
4. Acute hepatoxicity: fosphenytoin should be discontinued and not readministered.

FOSPHENYTOIN (Cerebyx)

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COMMENTS

1. Cerebyx (fosphenytoin) should not be confused with Celebrex (celecoxib) and Celexa
2.

3.
4.
5.
6.
7.

(citalopram). However, only the generic fosphenytoin product will be stocked to avoid this potential
confusion.
Fosphenytoin is a water soluble prodrug that is rapidly converted to phenytoin following parenteral
administration. The conversion half-life of fosphenytoin to phenytoin is approximately 15 minutes
with IV administration. Plasma total phenytoin concentrations peak in about 3 hours following IM
administration.
In patients with renal or hepatic disease, or in those with hypoalbuminemia, evaluating unbound
phenytoin concentrations may be more useful than total phenytoin serum concentrations.
Similar to phenytoin, fosphenytoin is contraindicated in patients with sinus bradycardia, sino-atrial
block, second and third degree A-V block, and Adams-Stokes syndrome.
Antiepileptic drugs should not be abruptly discontinued because of the possibility of increased seizure
frequency.
Initial symptoms of acute phenytoin toxicity are nystagmus, ataxia, and dysarthria. Other signs include
tremor, hyperreflexia, lethargy, slurred speech, nausea, vomiting, coma, and hypotension. Depression
of respiratory and circulatory systems may lead to death.
Fosphenytoin and phenytoin may interact with a number of medications. The following is a list of
selected drug interactions:
Drugs that may increase phenytoin concentrations:
Acute alcohol intake
Amiodarone
Diazepam
Isoniazid
Phenothiazines
Drugs that may decrease phenytoin concentrations:
Chronic alcohol abuse
Carbamazepine
Drugs that may increase or decrease phenytoin concentrations (and effects of phenytoin on
their concentrations are unpredictable)
Phenobarbital
Valproic acid
Drugs whose efficacy may be impaired by phenytoin include:
Warfarin
Estrogens
Oral contraceptives
Rifampin
Theophylline
Corticosteroids

REFERENCES
1.
2.
3.

AHFS Drug Information 2007. Bethesda, MD. ASHP Inc; 2007: 2213-2215
Cerebyx (fosphenytoin sodium) injection. Package insert. New York, NY: Warner-Lambert Co; 2001.
Poisindex. Micromedex. Search term: Fosphenytoin. Date accessed: 09/26/07.

Created 10-07

FOSPHENYTOIN (Cerebyx)

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