fosphenytoin sodium: clinical use

Prescribing considerations

• Prescribe, dispense and document exclusively in phenytoin sodium equivalents (PE); distinguish vial concentration from total vial content.
• Use controlled intravenous administration with continuous ECG, blood-pressure and respiratory monitoring and immediate access to resuscitation equipment.
• Review renal function, hepatic function, albumin, interacting medicines and pregnancy status where relevant; total phenytoin can misrepresent active unbound exposure in hypoalbuminaemia, renal or hepatic disease.
• Consider HLA-B*1502 testing before phenytoin exposure in patients of Han Chinese or Thai ancestry and other relevant Asian populations.
• Fosphenytoin is ineffective for absence seizures.

Contraindications and cautions

• Hypersensitivity to fosphenytoin, phenytoin, other hydantoins or product excipients
• Sinus bradycardia, sinoatrial block, second- or third-degree atrioventricular block, or Adams–Stokes syndrome
• Acute intermittent porphyria
• Concomitant delavirdine

Monitoring

• Continuous ECG, blood pressure and respiratory monitoring during intravenous administration and observation afterwards.
• Assess for hypotension, conduction disturbance, central nervous system depression and local tissue injury.
• Consider phenytoin concentrations for suspected toxicity, loss of seizure control, interactions, route or product changes, pregnancy or organ failure; free concentrations may be more informative when protein binding is reduced.
• Depending on clinical context, consider full blood count, liver function, renal profile and longer-term bone or vitamin D assessment.

Clinical pharmacology

Fosphenytoin is a highly protein-bound, water-soluble prodrug rapidly converted by phosphatases to phenytoin. Phenytoin limits sustained repetitive neuronal firing through voltage-dependent sodium-channel modulation. Its saturable CYP2C9 and CYP2C19 metabolism, protein binding and enzyme induction contribute to nonlinear pharmacokinetics and numerous interactions.

Formulation and product differences

• The selected product is a concentrate for intravenous infusion that may also be administered intramuscularly in selected adults.
• The labelled amount is expressed as phenytoin sodium equivalents rather than the mass of fosphenytoin sodium.
• Fosphenytoin and parenteral phenytoin have important preparation and administration differences and should not be treated as interchangeable products at the point of administration.
• Intramuscular administration is not recommended in children or for status epilepticus.