Overview
11 DESCRIPTION Fosphenytoin sodium injection, USP is a prodrug intended for parenteral administration; its active metabolite is phenytoin. 1.5 mg of fosphenytoin sodium USP is equivalent to 1 mg phenytoin sodium, and is referred to as 1 mg phenytoin sodium equivalents (PE). The amount and concentration of fosphenytoin is always expressed in terms of mg PE .
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Fosphenytoin is a prodrug of phenytoin and accordingly, its anticonvulsant effects are attributable to phenytoin. The precise mechanism by which phenytoin exerts its therapeutic effect has not been established but is thought to involve the voltage-dependent blockade of membrane sodium channels resulting in a reduction in sustained high-frequency neuronal discharges. 12.3 Pharmacokinetics Fosphenytoin Absorption Intravenous: When fosphenytoin sodium is administered by IV infusion, maximum plasma fosphenytoin concentrations are achieved at the end of the infusion. Intramuscular : Fosphenytoin is completely bioavailable following IM administration of fosphenytoin sodium. Peak concentrations occur at approximately 30 minutes postdose.
Indications
- 1 INDICATIONS AND USAGE Fosphenytoin sodium injection is indicated for the treatment of generalized tonic-clonic status epilepticus and prevention and treatment of seizures occurring during neurosurgery. Fosphenytoin sodium injection can also be substituted, short-term, for oral phenytoin. Fosphenytoin sodium injection should be used only when oral phenytoin administration is not possible [see Dosage and Administration (2.4) and Warnings and Precautions (5.2) ] .
Common Doses
- 20 mg
- 150 mg
- 2 mg
- 6 mg
Dosage
2 DOSAGE AND ADMINISTRATION The dose, concentration, and infusion rate of fosphenytoin sodium injection should always be expressed as phenytoin sodium equivalents (PE) ( 2.1 ) For Status Epilepticus: Adult loading dose is 15 to 20 mg PE/kg at a rate of 100 to 150 mg PE/min ( 2.3 ) Pediatric loading dose is 15 to 20 mg PE/kg at a rate of 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) ( 2.3 ) For Non-emergent Loading and Maintenance Dosing: Adult loading dose is 10 to 20 mg PE/kg given IV or IM; initial maintenance dose is 4 to 6 mg PE/kg/day in divided doses ( 2.
Black Box Warning
WARNING: CARDIOVASCULAR RISK ASSOCIATED WITH RAPID INFUSION RATES The rate of intravenous fosphenytoin sodium injection administration should not exceed 150 mg phenytoin sodium equivalents (PE) per minute in adults and 2 mg PE/kg/min (or 150 mg PE/min, whichever is slower) in pediatric patients because of the risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering intravenous fosphenytoin sodium injection.
Contraindications
- 4 CONTRAINDICATIONS Fosphenytoin sodium is contraindicated in patients with: A history of hypersensitivity to fosphenytoin sodium injection or its inactive ingredients, or to phenytoin or other hydantoins [see Warnings and Precautions (5.6) ] . Reactions have included angioedema. Sinus bradycardia, sino-atrial block, second and third degree A-V block, or Adams-Stokes syndrome because of the effect of parenteral phenytoin or fosphenytoin sodium on ventricular automaticity. A history of prior acute hepatotoxicity attributable to fosphenytoin sodium or phenytoin [see Warnings and Precautions (5.
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Cardiovascular Risk Associated with Rapid Infusion [see Warnings and Precautions (5.2) ] Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.3) ] Serious Dermatologic Reactions [see Warnings and Precautions (5.4) ] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.5) ] Hypersensitivity [see Warnings and Precautions (5.6) ] Angioedema [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Fosphenytoin is extensively bound to human plasma proteins. Drugs highly bound to albumin could increase the unbound fraction of fosphenytoin. Although, it is unknown whether this could result in clinically significant effects, caution is advised when administering fosphenytoin sodium with other drugs that significantly bind to serum albumin. The most significant drug interactions following administration of fosphenytoin sodium are expected to occur with drugs that interact with phenytoin.