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fosphenytoin sodium

Cerebyx, Pro-Epanutin (UK)

Pharmacologic class: Hydantoin

Therapeutic class: Anticonvulsant

Pregnancy risk category D


Thought to regulate neuronal membrane by promoting sodium excretion from neurons. This action prevents hyperexcitability and excessive stimulation, which inhibits spread of seizure activity. Lacks general CNS depressant effect.


Injection: 150 mg in 2-ml vials (100 mg phenytoin sodium), 750 mg in 10-ml vials (500 mg phenytoin sodium)

Indications and dosages

Status epilepticus

Adults: 15 to 20 mg phenytoin sodium equivalent (PE)/kg I.V. at 100 to 150 mg PE/minute as a loading dose, then 4 to 6 mg (PE)/kg I.V. daily for maintenance

To prevent seizures during neurosurgery

Adults: 10 to 20 mg PE/kg I.M. or I.V. as a loading dose, then 4 to 6 mg PE/kg I.M. or I.V. daily for maintenance

Dosage adjustment

• Hepatic disease

• Renal impairment

• Elderly patients


• Hypersensitivity to drug

• Adams-Stokes syndrome

• Arrhythmias


Use cautiously in:

• hepatic or renal impairment, severe cardiac or respiratory disease

• elderly patients

• pregnant or breastfeeding patients (safety not established).


• Know that drug is a phenytoin prodrug and is given in PE units to avoid the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses.

• For I.V. use, dilute in dextrose 5% in water or normal saline solution.

• Don't give faster than 150 mg PE/minute. Too-rapid infusion causes hypotension.

Check ECG, vital signs, and overall patient status continuously during infusion and for 10 to 20 minutes afterward.

• When giving I.M., rotate injection sites.

Adverse reactions

CNS: ataxia, agitation, dizziness, drowsiness, dysarthria, dyskinesia, speech disorder, extrapyramidal syndrome, headache, nervousness, weakness, confusion, hyperesthesia, paresthesia, cerebral edema, coma, intracranial hypertension

CV: hypotension, tachycardia

EENT: diplopia, nystagmus, tinnitus

GI: nausea, vomiting, constipation, dry mouth, anorexia

GU: pink, red, or reddish-brown urine

Hematologic: lymphadenopathy, aplastic anemia, agranulocytosis, leukopenia, megaloblastic anemia, thrombocytopenia

Hepatic: hepatitis

Metabolic: hypocalcemia, hypokalemia, hyperglycemia, increased glucose tolerance

Musculoskeletal: back or pelvic pain, osteomalacia

Skin: hypertrichosis, rash, pruritus, exfoliative dermatitis, Stevens-Johnson syndrome

Other: gingival hyperplasia, altered taste, fever, facial edema, weight loss, injection site pain, allergic reactions


Drug-drug. Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, estrogens, felbamate, fluconazole, fluoxetine, halothane, influenza vaccine, isoniazid, itraconazole, ketoconazole, methylphenidate, miconazole, omeprazole, phenothiazines, phenylbutazone, salicylates, sulfonamides, tolbutamide, trazodone: increased fosphenytoin blood level

Antidepressants, antihistamines, opioids, sedative-hypnotics: additive CNS depression

Barbiturates, carbamazepine, reserpine: decreased fosphenytoin blood level

Corticosteroids, cyclosporine, doxycycline, estrogens, felbamate, methadone, quinidine, rifampin: altered effects of these drugs

Dopamine: additive hypotension

Lidocaine, propranolol: additive cardiac depression

Streptozocin, theophylline: decreased efficacy of these drugs

Warfarin: initial increase in warfarin effects in patients stabilized on warfarin therapy, followed by decreased response to warfarin

Drug-diagnostic tests. Alkaline phosphatase, glucose, hepatic enzymes: increased levels

Dexamethasone, metyrapone: test interference

Glucose tolerance test: decreased tolerance

Potassium, thyroxine: decreased levels

Thyroid function tests: decreased values

Drug-behaviors. Acute alcohol ingestion: increased drug blood level, additive CNS depression

Chronic alcohol ingestion: decreased drug blood level

Patient monitoring

• Be prepared to slow administration or stop therapy if significant cardiovascular reactions occur.

• Monitor neurologic status carefully, especially for evidence of increasing intracranial pressure.

Assess for rash. Withhold drug and notify prescriber if it occurs.

• Monitor phenytoin blood level after drug has metabolized to phenytoin (about 2 hours after I.V. dose or 4 hours after I.M. dose).

• Monitor electrolyte levels.

• Evaluate blood glucose level. Watch for hyperglycemia in patients with diabetes.

Patient teaching

• Inform patient that he may experience sensory disturbances during I.V. administration.

Advise patient to immediately report adverse effects, particularly rash.

• Tell patient that drug may turn his urine pink, red, or reddish brown.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


(foss-fen-i-toyn) ,


(trade name)


Therapeutic: anticonvulsants
Pregnancy Category: D


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.


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.


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)

IMunknown30 minup to 24 hr
IV15–45 min15–60 minup to 24 hr


Contraindicated in: Hypersensitivity;Sinus bradycardia, sinoatrial block, 2nd- or 3rd-degree AV heart block or Adams-Stokes syndrome.Concurrent use of delavirdine.
Use Cautiously in: Hepatic or renal disease (↑ risk of adverse reactions; dose reduction recommended for hepatic impairment); Obstetric: 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.
Exercise Extreme Caution in: genetic implication Patients positive for HLA-B*1502 allele (unless exceptional circumstances exist where benefits clearly outweigh the risks).

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • drowsiness (most frequent)
  • nystagmus (most frequent)
  • agitation
  • brain edema
  • headache
  • stupor
  • vertigo

Ear, Eye, Nose, Throat

  • amblyopia
  • deafness
  • diplopia
  • tinnitus


  • hypotension (with rapid IV administration)
  • tachycardia


  • dry mouth
  • nausea
  • taste perversion
  • tongue disorder
  • vomiting


  • pruritus (most frequent)
  • purple glove syndrome
  • rash
  • stevens-johnson syndrome (life-threatening)
  • toxic epidermal necrolysis (life-threatening)


  • back pain


  • ataxia (most frequent)
  • dysarthria
  • extrapyramidal syndrome
  • hypesthesia
  • incoordination
  • paresthesia
  • tremor


  • pelvic pain


Drug-Drug interaction

May ↓ the 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, omeprazole, oxcarbazepine, phenothiazines, salicylates, sertraline, succinamides, sulfonamides, ticlopidine, topiramate, trazodone, voriconazole, andwarfarin may ↑ phenytoin blood levels.Barbiturates, bleomycin, carbamazepine, carboplatin, cisplatin, doxorubicin, folic acid, fosamprenavir, methotrexate, nelfinavir, reserpine, ritonavir, vigabatrin, and chronic ingestion of alcohol may ↓ phenytoin blood levels.Phenytoin may ↓ the effects of amiodarone, atorvastatin, benzodiazepines, carbamazepine, chloramphenicol, corticosteroids, cyclosporine, digoxin, disopyramide, doxycycline, efavirenz, estrogens, felbamate, fluconazole, fluvastatin, folic acid, furosemide, indinavir, irinotecan, itraconazole, ketoconazole, lamotrigine, lopinavir/ritonavir, methadone, mexiletine, nelfinavir, nisoldipine, oral contraceptives, oxcarbazepine, paclitaxel, paroxetine, posaconazole, propafenone, quetiapine, quinidine, rifampin, ritonavir, saquinavir, sertraline, simvastatin, tacrolimus, teniposide, theophylline, topiramate, tricyclic antidepressants, vitamin D, voriconazole, warfarin, and zonisamide.St. John's wort may ↓ levels


Note: Doses of fosphenytoin are expressed as phenytoin sodium equivalents [PE]Status Epilepticus
Intravenous (Adults) 15–20 mg PE/kg.
Nonemergent and Maintenance Dosing
Intravenous Intramuscular (Adults and Children > 16 yr) Loading dose—10–20 mg PE/kg. Maintenance dose—4–6 mg PE/kg/day.
Intravenous Intramuscular (Children 10–16 yr) 6–7 mg PE/kg/day.
Intravenous Intramuscular (Children 7–9 yr) 7–8 mg PE/kg/day.
Intravenous Intramuscular (Children 4–6 yr) 7.5–9 mg PE/kg/day.
Intravenous Intramuscular (Children 0.5–3 yr) 8–10 mg PE kg/day.
Intravenous Intramuscular (Infants) 5 mg PE kg/day.
Intravenous Intramuscular (Neonates) 5–8 mg PE/kg/day.

Availability (generic available)

Injection: 50 mg PE/mL

Nursing implications

Nursing assessment

  • Assess location, duration, frequency, and characteristics of seizure activity. EEG may be monitored periodically during therapy.
  • Monitor BP, 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. genetic implication Stevens-Johnson syndrome and toxic epidermal necrolysis are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502 (occurs almost exclusively in patients with Asian ancestry, including including Han Chinese, Filipinos, Malaysians, South Asian Indians, and Thais). Avoid using phenytoin or fosphenytoin as alternatives to carbamazepine for patients who test positive. 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.
  • Assess mental status (orientation, mood, behavior) before and periodically during therapy. Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
  • Monitor injection site frequently during therapy for edema, discoloration, and pain distal to the site of injection (described as "purple glove syndrome"). May or may not be associated with extravasation. The syndrome may not develop for several days after injection of phenytoin or fosphenytoin.
  • 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).
  • 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)


  • Do not confuse concentration of fosphenytoin with total amount of drug in vial.
    • 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 dose of fosphenytoin should be followed with the institution of maintenance anticonvulsant therapy.
  • Intravenous Administration
  • 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: alemtuzumab, aminocaproic acid, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, azithromycin, bivalirudin, bleomycin, carboplatin, carmustine, cisplatin, cyclophosphamide, cytarabine, dactinomycin, daptomycin, dexmedetomidine, dexrazoxane, diltiazem, docetaxel, doxacurium, doxorubicin liposomal, eptifibatide, ertapenem, etoposide, etoposide phosphate, fludarabine, fluorouracil, foscarnet, gemcitabine, granisetron, ifosfamide, leucovorin, levofloxacin, linezolid, lorazepam, mechlorethamine, meperidine, methotrexate, metronidazole, nesiritide, octreotide, oxaliplatin, oxytocin, paclitaxel, palonosetron, pamidronate, pantoprazole, pemetrexed, phenobarbital, piperacillin/tazobactam, potassium acetate, rocuronium, sodium acetate, tacrolimus, teniposide, thiotepa, tigecycline, tirofiban, vinblastine, vincristine, vinorelbine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: caspofungin, dolasetron, doxorubicin hydrochloride, epirubicin, fenoldopam, idarubicin, irinotecan, midazolam, mitoxantrone, moxifloxacin, mycophenolate, nicardipine, quinupristin/dalfopristin

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.
  • Instruct patients that behavioral changes, skin rash, fever, sore throat, mouth ulcers, easy bruising, petechiae, unusual bleeding, abdominal pain, chills, pale stools, dark urine, jaundice, severe nausea or vomiting, drowsiness, slurred speech, unsteady gait, swollen glands,or persistent headache should be reported to health care professional immediately. Advise patient and family to notify health care professional if thoughts about suicide or dying, attempts to commit suicide; new or worse depression; new or worse anxiety; feeling very agitated or restless; panic attacks; trouble sleeping; new or worse irritability; acting aggressive; being angry or violent; acting on dangerous impulses; an extreme increase in activity and talking, other unusual changes in behavior or mood occur.
  • 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. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or on the web at www.aedpregnancyregistry.org. Enrollment must be done by patients themselves.
  • Advise patient to carry identification describing disease process and medication regimen at all times.
  • 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.
Drug Guide, © 2015 Farlex and Partners


Fosphenytoin Pharmacology An IV agent for status epilepticus, which may replace IV Dilantin–phenytoin. Cf Celexa.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.
References in periodicals archive ?
The Fosphenytoin Sodium Injection USP, 75 mg/ml, (50 mg PE/ml), which have been packaged in 100 mg PE/2 ml and 500 mg PE/10 ml single-use vials, are generic version of Pfizer's Cerebyx Injection.
Cerebyx is a water-based injectable anticonvulsant used to prevent and treat seizures occurring during neurosurgery.
Network has received numerous reports of problems associated with these three drug names: Cerebyx[R] (anticonvulsant), Celebrex[R] (nonsteroidal anti-inflammatory), and Celexa[R] (antidepressant) ("Cerebyx, celebrex, and celexa: Similar names causing concerns," 1999).
ampicillin (Polycillin) ciprofloxacin (Cipro) Anticonvulsants: Act on the central nervous ethosuximide (Zarontin) system to reduce number fosphenytoin (Cerebyx) and severity of seizures.
Within just a few weeks of hitting the market, at least 40 documented errors were reported to the Institute for Safe Medication Practices, a non-profit, educational and watch dog organization for the pharmaceutical industry Confusion has occurred due to the similarity among three different medications: Celebrex, Celexa (an antidepressant), and Cerebyx (an anti-seizure medication).
Sound-alike/look-alike drugs--like the pain medication Celebrex, the antidepressant Celexa, and the antiseizure drug Cerebyx --can be easily confused, Cohen said.
Fosphenytoin (Cerebyx [R]) is a phosphate ester prodrug of phenytoin that can be administered either intravenously or intramuscularly.
Aromatic anticonvulsants include felbamate (Felbatol), fosphenytoin (Cerebyx), and primidone.
Fosphenytoin (Cerebyx) is a prodrug that is rapidly converted to phenytoin in the body, so the nurse might see this variation of the drug ordered for L.R.
-- PCS Health Systems is helping pharmacists avoid medication errors through a novel computer alert system that warns them about medications with similar names, specifically Celebrex, Celexa and Cerebyx.
Safety and tolerance of intramuscular fosphenytoin (Cerebyx) in patients requiring a loading dose of phenytoin.
* Cerebyx. Cerebyx (fosphenytoin) is a prodrug of phenytoin in an injectable form that can be administered intramuscularly or intravenously.