Classifications: hydantoin anticonvulsant agent;
Therapeutic: anticonvulsant

Prototype: Phenytoin
Pregnancy Category: D


150 mg, 750 mg vials


Prodrug of phenytoin that converts to the anticonvulsant phenytoin after parenteral administration. Thought to modulate the sodium channels of neurons, calcium flux across neuronal membranes, and enhance the sodium–potassium ATPase activity of neurons and glial cells.

Therapeutic Effect

The cellular mechanism of phenytoin is thought to be responsible for the anticonvulsant activity of fosphenytoin.


Control of generalized convulsive status epilepticus and the prevention and treatment of seizures during neurosurgery, or as a parenteral short-term substitute for oral phenytoin.

Unlabeled Uses

Antiarrhythmic agent especially in treatment of digitalis-induced arrhythmia; treatment of trigeminal neuralgia (tic douloureux).


Hypersensitivity to hydantoin products, rash, seizures due to hypoglycemia, sinus bradycardia, complete or incomplete heart block; Adams–Stokes syndrome; pregnancy (category D).

Cautious Use

Impaired liver or kidney function, alcoholism, hypotension, heart block, bradycardia, severe CAD, diabetes mellitus, hyperglycemia, respiratory depression, acute intermittent porphyria; lactation.

Route & Dosage

Status Epilepticus
Adult: IV Loading Dose 15–20 mg PE/kg (PE = phenytoin sodium equivalents) administered at 100–150 mg PE/min IV Maintenance Dose 4–6 mg PE/kg/d

Substitution for Oral Phenytoin Therapy
Adult: IV/IM Substitute fosphenytoin at the same total daily dose in mg PE as the oral dose at a rate of infusion not greater than 150 mg PE/min


  • Note: All dosing is expressed in phenytoin sodium equivalents (PE) to avoid the need to calculate molecular weight adjustments between fosphenytoin and phenytoin sodium doses. Always prescribe and fill fosphenytoin in PE units.
  • Follow institutional policy regarding maximum volume to inject into one IM site.

PREPARE: Direct: Dilute in DSW or NS to a concentration of 1.5–25 mg PE/mL.  

ADMINISTER: Direct: Do not administer at a rate >150 mg PE/min.  

INCOMPATIBILITIES Y-site: Fenoldopam, midazolam.

  • Store at 2°–8° C (36°–46° F); may store at room temperature not to exceed 48 h.

Adverse Effects (≥1%)

CNS: Usually dose related. Paresthesia, tinnitus, nystagmus, dizziness, somnolence, drowsiness, ataxia, mental confusion, tremors, insomnia, headache, seizures, increased reflexes, dysarthria, intracranial hypertension. CV: Bradycardia, tachycardia, asystole, hypotension, hypertension, cardiovascular collapse, cardiac arrest, heart block, ventricular fibrillation, phlebitis. Special Senses: Photophobia, conjunctivitis, diplopia, blurred vision. GI: Gingival hyperplasia, nausea, vomiting, constipation, epigastric pain, dysphagia, loss of taste, weight loss, hepatitis, liver necrosis. Hematologic: Thrombocytopenia, leukopenia, leukocytosis, agranulocytosis, pancytopenia, eosinophilia; megaloblastic, hemolytic, or aplastic anemias. Metabolic: Fever, hyperglycemia, glycosuria, weight gain, edema, transient increase in serum thyrotropic (TSH) level, hyperkalemia, osteomalacia or rickets associated with hypocalcemia and elevated alkaline phosphatase activity. Skin: Alopecia, hirsutism (especially in young female); rash: scarlatiniform, maculopapular, urticarial, morbilliform (may be fatal); bullous, exfoliative, or purpuric dermatitis; Stevens-Johnson syndrome, toxic epidermal necrolysis, keratosis, neonatal hemorrhage, pruritus. Urogenital: Acute renal failure, Peyronie's disease. Respiratory: Acute pneumonitis, pulmonary fibrosis. Musculoskeletal: Periarteritis nodosum, acute systemic lupus erythematosus, craniofacial abnormalities (with enlargement of lips). Other: Lymphadenopathy, injection site pain, chills.

Diagnostic Test Interference

Fosphenytoin may produce lower than normal values for dexamethasone or metyrapone tests; may increase serum levels of glucose, BSP, and alkaline phosphatase and may decrease PBI and urinary steroid levels.


Drug: Alcohol decreases effects; other anticonvulsants may increase or decrease fosphenytoin levels; fosphenytoin increases metabolism of corticosteroids, oral anticoagulants, and oral contraceptives, decreasing their effectiveness; amiodarone, chloramphenicol, omeprazole increase fosphenytoin levels; antituberculosis agents, voriconazole decrease fosphenytoin levels. Food: Folic acid, calcium, vitamin D absorption may be decreased by fosphenytoin; fosphenytoin absorption may be decreased by enteral nutrition supplements. Herbal: Ginkgo may decrease anticonvulsant effectiveness.


Absorption: Completely absorbed after IM administration. Peak: 30 min IM. Distribution: 95–99% bound to plasma proteins, displaces phenytoin from protein binding sites; crosses placenta, small amount in breast milk. Metabolism: Converted to phenytoin by phosphatases; phenytoin is oxidized in liver to inactive metabolites. Elimination: Half-life 15 min to convert fosphenytoin to phenytoin, 22 h phenytoin; phenytoin metabolites excreted in urine.

Nursing Implications

Note: See phenytoin for additional nursing implications.

Assessment & Drug Effects

  • Monitor ECG, BP, and respiratory function continuously during and for 10–20 min after infusion.
  • Discontinue infusion and notify physician if rash appears. Be prepared to substitute alternative therapy rapidly to prevent withdrawal-precipitated seizures.
  • Lab tests: Monitor CBC with differential, platelet count, serum electrolytes, and blood glucose.
  • Allow at least 2 h after IV infusion and 4 h after IM injection before monitoring total plasma phenytoin concentration.
  • Monitor diabetics for loss of glycemic control.
  • Monitor carefully for adverse effects, especially in patients with renal or hepatic disease or hypoalbuminemia.

Patient & Family Education

  • Be aware of potential adverse effects. Itching, burning, tingling, or paresthesia are common during and for some time following IV infusion.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

© 2006-2023 Last Updated On: 01/27/2023 (0)
Wait 20 seconds...!!!