Cerebyx
fosphenytoin sodium
Pharmacologic class: Hydantoin
Therapeutic class: Anticonvulsant
Pregnancy risk category D
Action
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.
Availability
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
Contraindications
• Hypersensitivity to drug
• Adams-Stokes syndrome
• Arrhythmias
Precautions
Use cautiously in:
• hepatic or renal impairment, severe cardiac or respiratory disease
• elderly patients
• pregnant or breastfeeding patients (safety not established).
Administration
• 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.
See 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
Interactions
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.
See 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.
See 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.
fosphenytoin
(foss-fen-i-toyn) fosphenytoin,Cerebyx
(trade name)Classification
Therapeutic: anticonvulsantsIndications
Action
Therapeutic effects
Pharmacokinetics
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
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
Cardiovascular
- hypotension (with rapid IV administration)
- tachycardia
Gastrointestinal
- dry mouth
- nausea
- taste perversion
- tongue disorder
- vomiting
Dermatologic
- pruritus (most frequent)
- purple glove syndrome
- rash
- stevens-johnson syndrome (life-threatening)
- toxic epidermal necrolysis (life-threatening)
Musculoskeletal
- back pain
Neurologic
- ataxia (most frequent)
- dysarthria
- extrapyramidal syndrome
- hypesthesia
- incoordination
- paresthesia
- tremor
Miscellaneous
- pelvic pain
Interactions
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 ↓ levelsRoute/Dosage
Note: Doses of fosphenytoin are expressed as phenytoin sodium equivalents [PE]Status EpilepticusAvailability (generic available)
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)Implementation
- 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.