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.
☞ 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.
☞ 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.