Fosfen

Fosphenytoin Sodium is a water-soluble prodrug of phenytoin, used for rapid seizure control and prevention of convulsive episodes.

Approved Indications:

• Status Epilepticus:
• Management of generalized tonic-clonic and complex partial seizures in adults and children.
• Seizure Prevention:
• Short-term seizure prophylaxis in neurosurgery, traumatic brain injury, or other acute neurological conditions.
• Conversion to Oral Therapy:
• Transition from intravenous to oral phenytoin therapy when oral administration is feasible.

Off-label / Clinically Accepted Uses:

• Acute management of seizures in critically ill or postoperative patients.
• Prevention of early post-traumatic seizures in selected adult and pediatric populations.
• Temporary seizure control in patients unable to tolerate oral anticonvulsants.

Adults:

• IV/IM Loading Dose: 15–20 mg PE/kg (phenytoin equivalents), administered at ≤150 mg PE/min IV.
• Maintenance Dose: 4–6 mg PE/kg/day IV or IM in divided doses every 8–12 hours.

Pediatrics:

• IV/IM Loading Dose: 15–20 mg PE/kg; infusion rate ≤3 mg PE/kg/min.
• Maintenance Dose: 4–8 mg PE/kg/day IV/IM in divided doses every 8–12 hours.

Special Populations:

• Elderly: Reduce infusion rate; monitor cardiac function.
• Renal impairment: Usually no adjustment required; monitor serum levels.
• Hepatic impairment: Dose reduction may be necessary; monitor liver function.

Administration Routes:

• Intravenous (IV) infusion preferred for rapid control; intramuscular (IM) if IV access unavailable.
• Continuous cardiac monitoring recommended during IV administration in high-risk patients.

Fosphenytoin is rapidly converted in vivo to phenytoin, which stabilizes neuronal membranes by inhibiting voltage-gated sodium channels. This prolongs the inactive state of the channels, reducing repetitive neuronal firing and seizure propagation. By limiting hyperexcitable neuronal activity, fosphenytoin effectively prevents and controls convulsive episodes in the central nervous system.

• Absorption: Rapid conversion to phenytoin after IV/IM administration; peak plasma levels in 15–60 minutes IV and 1–2 hours IM.
• Distribution: Widely distributed; 90% plasma protein bound.
• Metabolism: Hepatic metabolism via CYP2C9 and CYP2C19; nonlinear kinetics.
• Half-life: 7–42 hours, dose- and patient-dependent.
• Excretion: Mainly hepatic metabolism; <5% unchanged in urine.
• Onset of Action: Immediate with IV infusion; rapid seizure control.

• Pregnancy: FDA Category D; risk of congenital malformations (e.g., cleft lip, cardiac defects). Only use if benefits outweigh risks.
• Lactation: Excreted in breast milk; caution advised. Monitor infants for sedation or feeding difficulties.

• Primary Class: Anticonvulsant
• Subclass: Hydantoin derivative; prodrug of phenytoin

• Known hypersensitivity to fosphenytoin, phenytoin, or other hydantoin derivatives.
• Sinus bradycardia, sinoatrial block, or second- or third-degree AV block without pacemaker.
• History of acute hepatotoxicity related to phenytoin.

• Cardiovascular risk: Hypotension and arrhythmias may occur with rapid IV infusion; monitor closely.
• Hepatic impairment: Monitor liver function; hepatotoxicity possible.
• Dermatologic reactions: Severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Hematologic: Monitor for leukopenia, thrombocytopenia, or anemia.
• High-risk patients: Elderly, cardiac disease, or critically ill patients need close monitoring.

Common:

• CNS: Dizziness, ataxia, nystagmus, somnolence, headache.
• Cardiovascular: Hypotension, arrhythmias (rare).
• GI: Nausea, vomiting, constipation.

Serious / Rare:

• Severe hypersensitivity reactions including anaphylaxis.
• Stevens-Johnson syndrome, toxic epidermal necrolysis.
• Hematologic: Leukopenia, thrombocytopenia, megaloblastic anemia.
• Hepatic: Hepatotoxicity, elevated liver enzymes.

Timing & Severity:

• CNS effects occur within hours, dose-dependent.
• Severe dermatologic or hepatic effects require immediate discontinuation.

• CYP450 inducers (e.g., rifampin, carbamazepine): Reduce phenytoin levels.
• CYP450 inhibitors (e.g., fluconazole, amiodarone): Increase phenytoin levels, risk of toxicity.
• Other antiepileptics: Monitor levels; dose adjustments may be necessary.
• Warfarin: Alters INR; monitor coagulation parameters.
• Oral contraceptives: May reduce efficacy; consider alternative contraception.

• Fosphenytoin is preferred IV alternative to phenytoin for status epilepticus due to lower risk of infusion-related complications.
• Guidelines emphasize slow IV infusion rates (<150 mg PE/min adults; <3 mg PE/kg/min pediatrics) to reduce cardiovascular adverse events.
• Monitoring serum phenytoin levels is recommended to optimize therapy and avoid toxicity.

• Store at 20°C to 25°C (room temperature).
• Protect from light and moisture; do not freeze.
• Reconstituted solutions: Use immediately or store at 2°C–8°C for a maximum of 4 hours; discard unused portions.
• Use aseptic technique for IV/IM administration.