Can fosphenytoin be diluted in Normal Saline (NS) or Dextrose in Normal Saline (DNS)?

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Fosphenytoin Dilution Compatibility

Fosphenytoin can be diluted in both Normal Saline (NS) and 5% Dextrose solutions, but NOT in Dextrose in Normal Saline (DNS) combinations. 1

FDA-Approved Dilution Guidelines

The FDA label explicitly states that fosphenytoin should be diluted in either 5% Dextrose Injection OR 0.9% Sodium Chloride Injection (Normal Saline) to a concentration ranging from 1.5 to 25 mg PE/mL. 1

Specific Preparation Instructions

  • Maximum concentration: 25 mg PE/mL in any solution 1
  • Compatible diluents:
    • 0.9% Sodium Chloride Injection (Normal Saline) 1
    • 5% Dextrose Injection 1
  • Inspection required: Visually inspect for particulate matter and discoloration prior to administration 1
  • Single-dose use only: Discard any unused product after opening 1

Critical Distinction from Phenytoin

Unlike phenytoin, which must be diluted ONLY in normal saline due to precipitation with glucose-containing solutions, fosphenytoin's superior water solubility allows compatibility with dextrose solutions. 2, 3, 4, 5

Why Fosphenytoin is Different

  • Fosphenytoin has a pH of 8.6 compared to phenytoin's pH of 11-12, making it significantly more water-soluble 6, 5
  • The formulation does not contain propylene glycol (40%) or ethanol (10%) that are present in phenytoin preparations 7, 5
  • This improved solubility eliminates the precipitation issues seen with phenytoin in glucose-containing solutions 3, 4

Common Pitfall to Avoid

Do NOT confuse the vial concentration (50 mg PE/mL) with the total vial content. Fatal overdoses have occurred when clinicians misinterpreted the concentration to mean the total content was 50 mg PE, when vials actually contain 100 mg PE (2 mL vial) or 500 mg PE (10 mL vial). 1

Administration Rate Requirements

  • Adults: Maximum infusion rate of 150 mg PE/min 1
  • Pediatric patients: Maximum rate of 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) 1
  • Cardiac monitoring: Continuous ECG, blood pressure, and respiratory monitoring is essential during and after infusion 1

References

Guideline

Pediatric Seizure Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Safety of fosphenytoin sodium.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 1996

Research

Fosphenytoin: a novel phenytoin prodrug.

Pharmacotherapy, 1996

Research

Fosphenytoin in infants.

Journal of child neurology, 1998

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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