fosphenytoin sodium

fosphenytoin sodium

Cerebyx, Pro-Epanutin (UK)

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.

Route	Onset	Peak	Duration
I.V.	Rapid	Unknown	Up to 24 hr
I.M.	Unknown	30 min	Up to 24 hr

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.