Neonatal Drug Therapy Manual

Fosphenytoin

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Updated December 29, 2025 - 2:25pm

Alternate Name(s): 
Cerebyx
Classification: 
Anticonvulsivant
Original Date: 
June 2011
Revised Date: 
December 2025
Indications: 
  • Treatment of Phenobarbital resistant seizures
Administration: 
  • IV intermittent infusion:over 10 - 30 minutes
    • The rate of fosphenytoin administration should not exceed 2 mg of Phenytoin Equivalents (PE)/kg/min, due to increased risk of severe hypotension and cardiac arrhythmias 
  • IM
Dosage: 

***  Fosphenytoin should always be prescribed in mg of Phenytoin Equivalents (PE)

  • Loading dose: 20 mg PE/kg IV/IM
  • Maintenance dose: 5 - 8 mg/kg/day PE/kg/day IV/IM divided BID

* Start at lower end of dosing range and titrate upwards based on efficacy/side effects

 

Side Effects: 
  • CVS: hypotension (with rapid IV administration), vasodilation, tachycardia, bradycardia
    • Careful cardiac monitoring is needed during and after* the infusion. The risk of cardiovascular toxicity increases with high infusion rates; however these events have also been reported below the recommended infusion rate. Reduction in rate of administration may be needed.
  • Dermatologic: rash,exfoliative dermatitis
  • Endocrine/metabolic: hyperglycemia
  • Hematologic: neutropenia, thrombocytopenia, anemia
  • Local: pain on injection (less irritation at injection site and phlebitis than with phenytoin), paresthesia, pruritis

 

* approximately 10 to 20 minutes after the end of infusion

Parameters to Monitor: 
  • BP, HR
  • CBC with differential, platelets
  • Serum glucose
  • Liver enzymes
  • Therapeutic Phenytoin levels: 40 - 80 micromol/L
    • Usual sampling time:
      • After load: at least 2 hours after end of IV infusion or 4 hours after IM load injection
      • Maintenance: trough level for IV or IM administration (0 - 60 minutes before next dose) on day 3
Reconstitution and Stability: 

*** Dose, concentration and infusion rates are expressed as Phenytoin Equivalents (PE)

  • Fosphenytoin PE 50 mg/mL
    • Take 1 mL (PE 50 mg) and add to 9 mL of 0.9% NaCl
    • Final concentration: PE 5 mg/mL
  • Store vials in refrigerator.  Vials stable 48 hours at room temperature
Compatibility: 

- Solutions Compatible: D5W, D10W, 0.9 % NaCl, dextrose-saline combinations

- Y-site Compatible: lorazepam, phenobarbital, potassium chloride

- Incompatible: calcium gluconate, midazolam, TPN

Notes: 

*Dose, concentration and infusion rates are expressed as Phenytoin Equivalents (PE)

Fosphenytoin 1 mg PE = Phenytoin 1 mg

 

IM or IV substitution for oral Phenytoin:

Initial: Use the same total daily dose in PE of Fosphenytoin.  Monitor clinical response and Phenytoin serum levels to further guide dose adjustment after 3 - 4 days.  Plasma concentrations may increase slightly with this method since oral phenytoin is 90% bioavailable and phenytoin derived from IM or IV Fosphenytoin is 100% bioavailable.

 

  • Each 1 mg of PE contains 0.0037 mmol of phosphate
References: 
  • Taketomo CK, Hodding JH, Kraus DM.  Pediatric Dosage Handbook 17th Edition. Hudson: Lexi-Comp Inc; 2010
  • Lexi-Comp Online Drug Database (most recent access: Dec 2025)
  •  CEREBYX® Fosphenytoin Sodium Injection Product Monograph , 2022. 

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