BLACK BOX WARNING
- cardiac arrhythmias and hypotension may occur with rapid infusion; cardiac monitoring required; maximum infusion rate 150 mg phenytoin equivalents/minute
fosphenytoin
Brand: Cerebyx
⚠ BBW TDM Required Prototype: phenytoin
Drug Class: antiepileptic drug
Drug Family: antiepileptic
Subclass: phenytoin prodrug
Organ Systems: cns
Mechanism of Action
Water-soluble phosphate ester prodrug of phenytoin that is rapidly converted to phenytoin by phosphatases in blood and tissues. Phenytoin blocks voltage-gated Na+ channels in their inactivated state, preventing repetitive neuronal firing. Preferred over IV phenytoin as fosphenytoin is water-soluble, causes less infusion-site toxicity, and can be given IM.
voltage-gated sodium channels (Nav)
Indications
- status epilepticus
- prevention and treatment of perioperative seizures
- loading dose replacement for oral phenytoin when oral route is unavailable
Contraindications
- second or third degree heart block
- sinus bradycardia
- sinoatrial block
- Adams-Stokes syndrome
- hypersensitivity to phenytoin
Adverse Effects
Common
- pruritus
- paresthesias (perineal itching — classic)
- dizziness
- nystagmus
- headache
Serious
- cardiac arrhythmias
- hypotension (if infused too rapidly)
- purple glove syndrome (less likely than phenytoin IV)
- IV site reactions
- CNS depression
Pharmacokinetics (ADME)
| Absorption | IV or IM; complete conversion to phenytoin within 15 minutes (IV) or 30 minutes (IM) |
| Distribution | same as phenytoin; 90% protein bound (albumin) |
| Metabolism | phosphatases convert to phenytoin; phenytoin metabolized by CYP2C9/CYP2C19 |
| Excretion | renal (as phenytoin metabolites) |
| Half-life | 8–15 minutes (fosphenytoin); ~22 hours (phenytoin) |
| Onset | immediate (IV) |
| Peak | 15–30 minutes post-conversion |
| Duration | varies with phenytoin levels |
| Protein Binding | 90% (as phenytoin) |
| Vd | same as phenytoin |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | phenytoin inhibits and induces CYP2C9; complex bidirectional interaction; monitor INR closely | major |
| oral contraceptives | phenytoin induces CYP3A4, reducing OCP efficacy | major |
Nursing Considerations
- Dose expressed in phenytoin equivalents (PE); 1 mg PE = 1 mg phenytoin; double-check units.
- Maximum IV rate: 150 mg PE/min; monitor blood pressure and ECG continuously during infusion.
- Pruritus and paresthesias (especially perineal) are common during infusion — reassure patient, do not stop infusion unless severe.
- Monitor serum phenytoin levels after conversion; target total phenytoin 10–20 mcg/mL (adjust for albumin).
Clinical Pearls
- Fosphenytoin largely replaced IV phenytoin because it can be given IM (useful when IV access is difficult), is compatible with most IV solutions, and eliminates the propylene glycol toxicity and local tissue necrosis ('purple glove syndrome') associated with IV phenytoin.
- The characteristic perineal pruritus and paresthesias during fosphenytoin infusion are a predictable (though uncomfortable) pharmacodynamic effect of phosphate release; they are not allergic reactions.
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.